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Philipson E, Jabbar K, Bratlie SO, Hansson G, Persson J, Vilhav C, Wennerblom J, Sadik R, Naredi P, Bourghardt Fagman J, Engström C. Adjunct mucin biomarkers MUC2+MUC5AC and MUC5AC+PSCA in a clinical setting identify and may improve correct selection of high-risk pancreatic lesions for surgery. HPB (Oxford) 2025; 27:214-221. [PMID: 39562183 DOI: 10.1016/j.hpb.2024.10.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 10/29/2024] [Indexed: 11/21/2024]
Abstract
BACKGROUND Pancreatic cancer has dismal prognosis with a 5-year survival of 12 %. Cystic lesions have been identified as premalignant lesions. The challenge is to identify lesions with high risk of malignant progression, to offer patients prophylactic curative pancreatic surgery. Previous studies have identified mucin biomarker panels (MUCPs) as potential discriminators of pre- and malignant pancreatic cystic lesions. The present study assessed whether MUCPs contribute to more accurate identification of patients with high-risk pancreatic lesions and improve selection for surgery. METHODS This retrospective crossover study included 88 patients referred to endoscopic ultrasound because of unclear pancreatic cystic lesions. Clinical management and surgical decision-making with and without MUCP values were assessed by two expert teams with access to patient medical history, radiology, fine-needle aspirates, cytology, and cystic fluid carcinoembryonic antigen. RESULTS The adjunct of MUCPs improved decision-making in 2 of 21 cases with surgical pathology, identifying one cancer that otherwise would have been missed and sparing one patient from unnecessary surgery. CONCLUSION Access to MUCPs in a clinical setting improved correct selection of high-risk pancreatic lesions for surgery in single cases. A higher number of incorrect recommendations for surgery with the adjunct of MUCPs was also noted, which calls for caution.
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Affiliation(s)
- Eva Philipson
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
| | - Karolina Jabbar
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Sweden; Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Sweden
| | - Svein-Olav Bratlie
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Gunnar Hansson
- Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Sweden
| | - Jan Persson
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Caroline Vilhav
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Johanna Wennerblom
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Riadh Sadik
- Department of Medicine, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital, Sweden
| | - Peter Naredi
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Johan Bourghardt Fagman
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Cecilia Engström
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden
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Cao YY, Lv XJ, Li H, Qian LC, Si HP, Li Y, Guo K, Ren S, Wang ZQ. Serum High-Density Lipoprotein Cholesterol Concentrations in Pancreatic Ductal Adenocarcinoma and Its Association With Histological Grade in a Chinese Population. Cancer Control 2025; 32:10732748251316602. [PMID: 39927839 PMCID: PMC11811967 DOI: 10.1177/10732748251316602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 12/12/2024] [Accepted: 01/06/2025] [Indexed: 02/11/2025] Open
Abstract
BACKGROUND Serum high-density lipoprotein cholesterol (HDL-c) may influence cancer development. However, its relationship with the histological grade of pancreatic ductal adenocarcinoma (PDAC) is not well understood. This study aims to explore the potential associations between serum HDL-c levels and different histological grades of PDAC. METHODS This retrospective study included 181 patients with pathologically confirmed PDAC who underwent radical surgery. Clinical data, blood biochemical results, imaging features, and pathological details of the patients were collected, such as age, gender, diabetes, hypertension, tumor grade, tumor size and location, high-density lipoprotein (HDL-c), low-density lipoprotein (LDL), total cholesterol (TC), triglycerides (TG), carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA). RESULTS Patients with high-grade PDAC had significantly lower HDL-c levels compared to those with low-grade PDAC across both training and validation cohorts (P < 0.05). Significant associations were found between HDL-c levels and high-grade PDAC in the training (P < 0.001) and validation (P = 0.044) groups. Moreover, HDL-c levels were inversely related to lymph node metastasis in the training (P = 0.001) and validation (P = 0.012) sets. CONCLUSIONS Lower HDL-c levels are associated with high-grade PDAC and lymph node metastasis, suggesting that HDL-c may play a protective role in the progression of PDAC.
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Affiliation(s)
- Ying-Ying Cao
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Xiao-Jing Lv
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Hui Li
- Department of Pathology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Li-Chao Qian
- Department of Geratology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
| | - Hai-Peng Si
- Department of Pathology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Yuan Li
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Kai Guo
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Shuai Ren
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhong-Qiu Wang
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
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Tanaka H, Mise Y, Takahashi A, Kawano F, Takeda Y, Imamura H, Ichida H, Yoshioka R, Saiura A. Analyzing the high frequency of false-positive carcinoembryonic antigen elevations in postoperative pancreatic ductal adenocarcinoma. Langenbecks Arch Surg 2024; 410:6. [PMID: 39672933 DOI: 10.1007/s00423-024-03577-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Accepted: 12/09/2024] [Indexed: 12/15/2024]
Abstract
PURPOSE The dynamics of postoperative carcinoembryonic antigen (CEA) in pancreatic ductal adenocarcinoma (PDAC) patients have not been well assessed. This study investigated the correlation between postoperative CEA elevations and tumor recurrence. METHODS Medical records were retrospectively analyzed for 84 patients who received curative resection for PDAC from January 2019 to December 2020. Postoperative CEA levels were monitored for a minimum of 12 months. False-positive CEA elevation was defined as a CEA level exceeding 5 ng/mL without evidence of recurrence in imaging studies. RESULTS Of the examined patients, 59 (70%) exhibited CEA > 5 ng/mL within the observation period. The sensitivity and specificity of elevated CEA levels for detecting recurrence were 84% and 41%, respectively. CEA elevations without tumor recurrence were observed in 27 patients, indicating a false-positive rate of 59%. More than half of these patients demonstrated peak CEA levels between 5 and 10 ng/mL, while only true-positive patients exhibited CEA levels exceeding 40.0 ng/mL. CONCLUSION CEA may rise in more than half of postoperative PDAC patients without recurrence. CEA alone is not a robust postoperative marker.
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Affiliation(s)
- Haruka Tanaka
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Yoshihiro Mise
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
| | - Atsushi Takahashi
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Fumihiro Kawano
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Yoshinori Takeda
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Hiroshi Imamura
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Hirofumi Ichida
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Ryuji Yoshioka
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Akio Saiura
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
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Shin KI, Yoon MS, Kim JH, Jang WJ, Leem G, Jo JH, Chung MJ, Park JY, Park SW, Hwang HK, Kang CM, Kim S, Park M, Lee HS, Bang S. Long-Term Outcomes of Neoadjuvant Therapy Versus Upfront Surgery for Resectable Pancreatic Ductal Adenocarcinoma. Cancer Med 2024; 13:e70363. [PMID: 39552022 PMCID: PMC11570550 DOI: 10.1002/cam4.70363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 09/17/2024] [Accepted: 10/13/2024] [Indexed: 11/19/2024] Open
Abstract
INTRODUCTION This study aimed to compare the long-term effects of neoadjuvant therapy and upfront surgery on overall survival (OS) and progression-free survival (PFS) in patients with resectable pancreatic ductal adenocarcinoma (PDAC). METHODS We retrospectively analyzed 202 patients, including 167 who had upfront surgery and 35 who received neoadjuvant therapy followed by surgery. Surgical outcomes and survival rates were compared using propensity score matching to minimize selection bias. RESULTS Neoadjuvant therapy showed significantly longer 75% OS (72.7 months vs. 28.3 months, p = 0.032) and PFS (29.6 months vs. 13.2 months, p < 0.001) compared to upfront surgery. Additionally, neoadjuvant therapy demonstrated significant improvements in surgical outcomes, including higher R0 resection rates (74.3% vs. 49.5%, p = 0.034), reduced tumor size (22.0 mm vs. 28.0 mm, p = 0.001), and decreased lymphovascular invasion (20.0% vs. 52.4%, p = 0.001). CONCLUSION Our study demonstrates the potential benefits of neoadjuvant therapy for resectable PDAC. The improved survival rates, delayed disease progression, and enhanced surgical outcomes underscore the potential of neoadjuvant therapy in addressing this aggressive disease. Despite limitations such as the retrospective design and small sample size, these findings support the effectiveness of neoadjuvant therapy in improving treatment outcomes for PDAC patients in real-world settings. Further prospective studies are required to validate these results.
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Affiliation(s)
- Kyung In Shin
- Division of Gastroenterology, Department of Internal MedicineYonsei University College of MedicineSeoulKorea
| | - Min Sung Yoon
- Division of Gastroenterology, Department of Internal MedicineYonsei University College of MedicineSeoulKorea
| | - Jee Hoon Kim
- Division of Gastroenterology, Department of Internal MedicineYonsei University College of MedicineSeoulKorea
| | - Won Joon Jang
- Division of Gastroenterology, Department of Internal MedicineYonsei University College of MedicineSeoulKorea
| | - Galam Leem
- Division of Gastroenterology, Department of Internal MedicineYonsei University College of MedicineSeoulKorea
- Institute of GastroenterologyYonsei University College of MedicineSeoulKorea
| | - Jung Hyun Jo
- Division of Gastroenterology, Department of Internal MedicineYonsei University College of MedicineSeoulKorea
- Institute of GastroenterologyYonsei University College of MedicineSeoulKorea
| | - Moon Jae Chung
- Division of Gastroenterology, Department of Internal MedicineYonsei University College of MedicineSeoulKorea
- Institute of GastroenterologyYonsei University College of MedicineSeoulKorea
| | - Jeong Youp Park
- Division of Gastroenterology, Department of Internal MedicineYonsei University College of MedicineSeoulKorea
- Institute of GastroenterologyYonsei University College of MedicineSeoulKorea
| | - Seung Woo Park
- Division of Gastroenterology, Department of Internal MedicineYonsei University College of MedicineSeoulKorea
- Institute of GastroenterologyYonsei University College of MedicineSeoulKorea
| | - Ho Kyoung Hwang
- Department of Hepatobiliary and Pancreatic SurgeryYonsei University College of MedicineSeoulKorea
| | - Chang Moo Kang
- Department of Hepatobiliary and Pancreatic SurgeryYonsei University College of MedicineSeoulKorea
| | - Seung‐seob Kim
- Department of Hepatobiliary and Pancreatic SurgeryYonsei University College of MedicineSeoulKorea
| | - Mi‐Suk Park
- Department of Radiology, Research Institute of Radiological ScienceYonsei University College of MedicineSeoulKorea
| | - Hee Seung Lee
- Division of Gastroenterology, Department of Internal MedicineYonsei University College of MedicineSeoulKorea
- Institute of GastroenterologyYonsei University College of MedicineSeoulKorea
| | - Seungmin Bang
- Division of Gastroenterology, Department of Internal MedicineYonsei University College of MedicineSeoulKorea
- Institute of GastroenterologyYonsei University College of MedicineSeoulKorea
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Gong J, Zhang Q, Peng Q, Shi D. Identification of Chronic Pancreatitis Associated microRNAs and Genes for the Diagnosis of Pancreatic Cancer. Am Surg 2024; 90:2797-2807. [PMID: 38708574 DOI: 10.1177/00031348241253801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/07/2024]
Abstract
OBJECTIVE The timely identification of both malignant and nonmalignant pancreatic lesions has the potential to significantly enhance prognosis and implement risk management strategies across various levels. microRNAs (miRs) and their corresponding targets play a crucial role in the development of pancreatic lesions and can serve as valuable diagnostic and therapeutic targets. The objective of our study was to investigate potential diagnostic markers that can effectively differentiate between malignant and nonmalignant pancreatic lesions. METHODS Gene Expression Omnibus (GEO) database with GSE24279 dataset was utilized to screen differentially expressed miRNAs (DEMs). We utilized the TargetScanHuman database to predict the target genes associated with hsa-miR-150-3p, hsa-miR-150-5p, and hsa-miR-214-3p. Furthermore, a cohort comprising healthy individuals (n = 52), chronic pancreatitis (CP; n = 34), and pancreatic adenocarcinoma (PAAD; n = 53) patients was recruited to ascertain the levels of plasma markers. RESULTS We identified 3 miRNAs (hsa-miR-150-3p, hsa-miR-150-5p, and hsa-miR-214-3p) and 2 proteins (PCDH1 and AMN) as potential diagnostic markers for distinguishing between CP and PAAD. The area under the curve (AUC) values for all markers exceeded .800. Notably, a combination of plasma PCDH1 and AMN demonstrated excellent diagnostic performance (AUC = .921; 95% CI: .866-.977; sensitivity = .792; specificity = .941) in discriminating between CP and PAAD. In addition, the model of hsa-miR-150-3p, hsa-miR-150-5p, and hsa-miR-214-3p yielded an AUC of .928, sensitivity of .830, and specificity of .912, respectively. CONCLUSION Plasma levels of miRNAs (hsa-miR-150-3p, hsa-miR-150-5p, and hsa-miR-214-3p) and their corresponding targets (PCDH1 and AMN) hold promise as potential biomarkers for predicting PAAD in patients with CP.
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Affiliation(s)
- Jing Gong
- Department of Medical Laboratory, Jiangxi Integrated Traditional Chinese and Western Medicine Hospital, Nanchang City, Jiangxi Province, China
| | - Qinghua Zhang
- Department of Medical Laboratory, Jiangxi Integrated Traditional Chinese and Western Medicine Hospital, Nanchang City, Jiangxi Province, China
| | - Qimin Peng
- Department of Medical Laboratory, Jiangxi Integrated Traditional Chinese and Western Medicine Hospital, Nanchang City, Jiangxi Province, China
| | - Dongling Shi
- Department of Health examination, Jiangxi Integrated traditional Chinese and Western Medicine Hospital, Nanchang City, Jiangxi Province, China
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Zheng J, He B, Deng L, Zhu X, Li R, Chen K, Zheng C, Wang D, Wang Y, Yu C, Chen G. Prognostic value of diffuse reduction of spleen density on postoperative survival of pancreatic ductal adenocarcinoma: A retrospective study. Asia Pac J Clin Oncol 2024; 20:275-284. [PMID: 36748794 DOI: 10.1111/ajco.13936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 07/05/2022] [Accepted: 01/07/2023] [Indexed: 02/08/2023]
Abstract
PURPOSE It is difficult to predict the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) before radical operation. The purpose of this study was to explore the connection between the diffuse reduction of spleen density on computed tomography (DROSD) and the postoperative prognosis of patients with PDAC. PATIENTS AND METHODS A total of 160 patients with PDAC who underwent radical surgery in the First Affiliated Hospital of Wenzhou Medical University were enrolled. Cox regression analysis was used to cast the overall survival (OS) and evaluate the prognostic factors. Nomogram was used to forecast the possibility of 1-year, 3-year, and 5-year OS. The prediction accuracy and clinical net benefit are performed by concordance index (C-index), calibration curve, time-dependent receiver operating characteristics (tdROC), and decision curve analysis. RESULTS In multivariable Cox analysis, DROSD is independently related to OS. Advanced age, TNM stage, neutrophil/lymphocyte ratio, and severe complications were also independent prognostic factors. The calibration curves of nomogram showed optimal agreement between prediction and observation. The C-index of nomogram is 0.662 (95%CI, 0.606-0.754). The area under tdROC curve for a 3-year OS of nomogram is 0.770. CONCLUSION DROSD is an independent risk factor for an OS of PDAC. We developed a nomogram that combined imaging features, clinicopathological factors, and systemic inflammatory response to provide a personalized risk assessment for patients with PDAC.
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Affiliation(s)
- Jiuyi Zheng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
| | - Bangjie He
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
| | - Liming Deng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
| | - Xuewen Zhu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
| | - Rizhao Li
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
| | - Kaiyu Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
| | - Chongming Zheng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
| | - Daojie Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
| | - Yi Wang
- Department of Epidemiology and Biostatistics, School of Public Health and Management, Wenzhou Medical University, Wenzhou, People's Republic of China
| | - Chang Yu
- Department of Interventional Therapy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
| | - Gang Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China
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Meng S, Hara T, Sato H, Tatekawa S, Tsuji Y, Saito Y, Hamano Y, Arao Y, Gotoh N, Ogawa K, Ishii H. Revealing neuropilin expression patterns in pancreatic cancer: From single‑cell to therapeutic opportunities (Review). Oncol Lett 2024; 27:113. [PMID: 38304169 PMCID: PMC10831399 DOI: 10.3892/ol.2024.14247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 10/13/2023] [Indexed: 02/03/2024] Open
Abstract
Pancreatic cancer, one of the most fatal types of human cancers, includes several non-epithelial and stromal components, such as activated fibroblasts, vascular cells, neural cells and immune cells, that are involved in different cancers. Vascular endothelial cell growth factor 165 receptors 1 [neuropilin-1 (NRP-1)] and 2 (NRP-2) play a role in the biological behaviors of pancreatic cancer and may appear as potential therapeutic targets. The NRP family of proteins serve as co-receptors for vascular endothelial growth factor, transforming growth factor β, hepatocyte growth factor, fibroblast growth factor, semaphorin 3, epidermal growth factor, insulin-like growth factor and platelet-derived growth factor. Investigations of mechanisms that involve the NRP family of proteins may help develop novel approaches for overcoming therapy resistance in pancreatic cancer. The present review aimed to provide an in-depth exploration of the multifaceted roles of the NRP family of proteins in pancreatic cancer, including recent findings from single-cell analysis conducted within the context of pancreatic adenocarcinoma, which revealed the intricate involvement of NRP proteins at the cellular level. Through these efforts, the present study endeavored to further reveal their relationships with different biological processes and their potential as therapeutic targets in various treatment modalities, offering novel perspectives and directions for the treatment of pancreatic cancer.
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Affiliation(s)
- Sikun Meng
- Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
| | - Tomoaki Hara
- Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
| | - Hiromichi Sato
- Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
| | - Shotaro Tatekawa
- Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
| | - Yoshiko Tsuji
- Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
| | - Yoshiko Saito
- Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
| | - Yumiko Hamano
- Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
| | - Yasuko Arao
- Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
| | - Noriko Gotoh
- Division of Cancer Cell Biology, Cancer Research Institute of Kanazawa University, Kanazawa, Ishikawa 920-1192, Japan
| | - Kazuhiko Ogawa
- Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
| | - Hideshi Ishii
- Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
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Wei ZJ, Zhou BC, Wang GX, Han WX, Li YX, Xu AM. Diagnosis of colorectal cancer based on folate receptor-positive circulating tumor cell analysis: a retrospective cohort study. Int J Clin Oncol 2024; 29:149-158. [PMID: 38112831 DOI: 10.1007/s10147-023-02435-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 11/04/2023] [Indexed: 12/21/2023]
Abstract
BACKGROUND Early diagnosis and treatment are crucial to improve the prognosis of colorectal cancer (CRC). At present, there is a lack of an accurate CRC screening factor. We conducted folate receptor-positive circulating tumor cell analysis (FR + CTC analysis) in distinguishing CRC from benign colorectal diseases to evaluate the diagnostic efficiency. METHODS Clinical data of patients admitted to The First Affiliated Hospital of Anhui Medical University from January 2021 to July 2022 were retrospectively collected. Levels of FR + CTC and other indicators were analyzed. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance of these molecular biomarkers. RESULTS Data of 103 patients with CRC and 54 patients with benign colorectal diseases were collected. FR + CTC levels were observed significantly higher in CRC patients than in patients with benign colorectal diseases (P < 0.001). FR + CTC level was correlated with tumor diameter, differentiation, T-stage, pathological stage, clinical stage, and intravascular tumor thrombus in patients with CRC (P < 0.05). The optimal cutoff value of FR + CTC level for diagnosing CRC patients was 7.66 FU/3 ml, with a sensitivity of 85.4%, a specificity of 74.1%, and an Area Under Curve (AUC) of 0.855 (95% CI 0.77-0.923). In < 50-years old patients with CRC, the diagnostic efficiency of FR + CTC was excellent, with an AUC of 0.936 (95% CI 0.877-0.995). CONCLUSION FR + CTC counting has excellent diagnostic efficiency in screening of CRC. FR + CTC count can also predict the tumor stage of CRC patients before surgery, and guide the choice of treatment.
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Affiliation(s)
- Zhi-Jian Wei
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China
| | - Bai-Chuan Zhou
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China
| | - Guo-Xing Wang
- Anhui Hanhai Boxing Biotechnology Co., LTD, Hefei, 231699, Anhui, China
| | - Wen-Xiu Han
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China.
| | - Yong-Xiang Li
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China.
| | - A-Man Xu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China.
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Pourali G, Kazemi D, Chadeganipour AS, Arastonejad M, Kashani SN, Pourali R, Maftooh M, Akbarzade H, Fiuji H, Hassanian SM, Ghayour-Mobarhan M, Ferns GA, Khazaei M, Avan A. Microbiome as a biomarker and therapeutic target in pancreatic cancer. BMC Microbiol 2024; 24:16. [PMID: 38183010 PMCID: PMC10768369 DOI: 10.1186/s12866-023-03166-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 12/18/2023] [Indexed: 01/07/2024] Open
Abstract
Studying the effects of the microbiome on the development of different types of cancer has recently received increasing research attention. In this context, the microbial content of organs of the gastrointestinal tract has been proposed to play a potential role in the development of pancreatic cancer (PC). Proposed mechanisms for the pathogenesis of PC include persistent inflammation caused by microbiota leading to an impairment of antitumor immune surveillance and altered cellular processes in the tumor microenvironment. The limited available diagnostic markers that can currently be used for screening suggest the importance of microbial composition as a non-invasive biomarker that can be used in clinical settings. Samples including saliva, stool, and blood can be analyzed by 16 s rRNA sequencing to determine the relative abundance of specific bacteria. Studies have shown the potentially beneficial effects of prebiotics, probiotics, antibiotics, fecal microbial transplantation, and bacteriophage therapy in altering microbial diversity, and subsequently improving treatment outcomes. In this review, we summarize the potential impact of the microbiome in the pathogenesis of PC, and the role these microorganisms might play as biomarkers in the diagnosis and determining the prognosis of patients. We also discuss novel treatment methods being used to minimize or prevent the progression of dysbiosis by modulating the microbial composition. Emerging evidence is supportive of applying these findings to improve current therapeutic strategies employed in the treatment of PC.
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Affiliation(s)
- Ghazaleh Pourali
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Danial Kazemi
- Student Research Committee, Isfahan University of Medical Sciences, Hezar Jerib Street, Isfahan, Iran
| | | | - Mahshid Arastonejad
- Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA
| | | | - Roozbeh Pourali
- Student Research Committee, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Mina Maftooh
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamed Akbarzade
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamid Fiuji
- Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Mahdi Hassanian
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Ghayour-Mobarhan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- Brighton & Sussex Medical School, Department of Medical Education, Falmer, Brighton, Sussex, BN1 9PH, UK
| | - Majid Khazaei
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Avan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- College of Medicine, University of Warith Al-Anbiyaa, Karbala, Iraq.
- School of Mechanical, Medical and Process Engineering, Science and Engineering Faculty, Queensland University of Technology, 2 George St, Brisbane City, QLD, 4000, Australia.
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Wu Y, Zhou J, Kou Q, Sun L, Ma Y, Yang T, Hu X. Establishment of a Prognostic Model for Pancreatic Cancer Based on Hypoxia-Related Genes. Technol Cancer Res Treat 2024; 23:15330338241288687. [PMID: 39431298 PMCID: PMC11504279 DOI: 10.1177/15330338241288687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 08/17/2024] [Accepted: 09/10/2024] [Indexed: 10/22/2024] Open
Abstract
OBJECTIVES Pancreatic cancer presents a formidable challenge with its aggressive nature and dismal prognosis, often hampered by elusive early symptoms. The tumor microenvironment (TME) emerges as a pivotal player in pancreatic cancer progression and treatment responses, characterized notably by hypoxia and immunosuppression. In this study, we aimed to identify hypoxia-related genes and develop a prognostic model for pancreatic cancer leveraging these genes. METHODS Through analysis of gene expression data from The Cancer Genome Atlas (TCGA) and subsequent GO/KEGG enrichment analysis, hypoxia-related pathways were identified. We constructed a prognostic model using lasso regression and validated it using an independent dataset. RESULTS Our results showed that expression levels of PLAU, SLC2A1, and CA9 exhibited significant associations with prognosis in pancreatic cancer. The prognostic model, built upon these genes, displayed robust predictive accuracy and was validated in an independent dataset. Furthermore, we found a correlation between the risk score of the prognostic model and clinical parameters of pancreatic cancer patients. At the same time, we also explored the relationship between the established hypoxia-related prognostic model and the immune microenvironment at the single-cell level. RT-qPCR results showed notable differences in the expression of hypoxia pathway-related genes between normal PANC-1 and hypoxic-treated PANC-1 cells. CONCLUSION Our study provides insights into the role of the hypoxic microenvironment in pancreatic cancer and offers a promising prognostic tool for clinical application.
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Affiliation(s)
- Yangdong Wu
- Department of Hepatobiliary Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Jianrui Zhou
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Qingyan Kou
- Department of Hepatobiliary Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Lin Sun
- Department of ICU, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yuan Ma
- Department of ICU, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Tingting Yang
- Department of ICU, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiao Hu
- Department of Hepatobiliary Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
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Qian L, Li J, Sun Y, Chai W, Deng X, Wang W, Shen B. Pancreatic index: A prognostic factor of upfront surgery for body or tail pancreatic ductal adenocarcinoma with vascular involvement-A retrospective study. Cancer Med 2023; 12:21199-21208. [PMID: 37933476 PMCID: PMC10726763 DOI: 10.1002/cam4.6687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 09/06/2023] [Accepted: 10/26/2023] [Indexed: 11/08/2023] Open
Abstract
BACKGROUND The pancreatic index (PI) is a useful preoperative imaging predictor for pancreatic ductal adenocarcinoma (PDAC). In this retrospective study, we determined the predictive effect of PI to distinguish patients of pancreatic body/tail cancer (PBTC) with vascular involvement who can benefit from upfront surgery. METHOD All patients who received distal pancreatectomy for PDAC from 2016 to 2020 at the Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine were considered for the study. A total of 429 patients with PBTC were assessed in relation to the value of PI. Fifty-five patients were eventually included and divided into low PI group and 29 patients in the normal PI group. RESULTS The median overall survival (mOS) was significantly shorter in the low PI group (13.1 vs. 30.0 months, p = 0.002) in this study, and PI ≥ 0.78 (OR = 0.552, 95% CI: 0.301-0.904, p = 0.020) was an independent influencing factor confirmed by multivariate analysis. Subgroup analysis showed that PI was an independent prognostic factor for LA-PBTC (OR = 0.272, 95% CI: 0.077-0.969, p = 0.045). As for BR PBTC, PI (OR = 0.519, 95% CI: 0.285-0.947, p = 0.033) combined with carbohydrate antigen 125 (CA125) (OR = 2.806, 95% CI: 1.206-6.526, p = 0.017) and chemotherapy (OR = 0.327, 95% CI: 0.140-0.763, p = 0.010) were independent factors. CONCLUSION This study suggests that the PI can be used as a predictive factor to optimize the surgical indication for PBTC with vascular involvement. Preoperative patients with normal PI and CA125 can achieve a long-term prognosis comparable to that of resectable PBTC patients.
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Affiliation(s)
- Lihan Qian
- Department of General SurgeryPancreatic Disease Center, Ruijin Hospital Shanghai Jiaotong University School of MedicineShanghaiChina
- Research Institute of Pancreatic DiseaseShanghai Jiaotong University School of MedicineShanghaiChina
- State Key Laboratory of Oncogenes and Related GenesShanghai Jiaotong UniversityShanghaiChina
| | - Jingfeng Li
- Department of General SurgeryPancreatic Disease Center, Ruijin Hospital Shanghai Jiaotong University School of MedicineShanghaiChina
- Research Institute of Pancreatic DiseaseShanghai Jiaotong University School of MedicineShanghaiChina
- State Key Laboratory of Oncogenes and Related GenesShanghai Jiaotong UniversityShanghaiChina
| | - Yanjun Sun
- Department of CardiovascularRuijin Hospital, Shanghai Jiao Tong University School of MedicineShanghaiChina
| | - Weimin Chai
- Department of RadiologyRuijin Hospital, Shanghai Jiao Tong University School of MedicineShanghaiChina
| | - Xiaxing Deng
- Department of General SurgeryPancreatic Disease Center, Ruijin Hospital Shanghai Jiaotong University School of MedicineShanghaiChina
- Research Institute of Pancreatic DiseaseShanghai Jiaotong University School of MedicineShanghaiChina
- State Key Laboratory of Oncogenes and Related GenesShanghai Jiaotong UniversityShanghaiChina
| | - Weishen Wang
- Department of General SurgeryPancreatic Disease Center, Ruijin Hospital Shanghai Jiaotong University School of MedicineShanghaiChina
- Research Institute of Pancreatic DiseaseShanghai Jiaotong University School of MedicineShanghaiChina
- State Key Laboratory of Oncogenes and Related GenesShanghai Jiaotong UniversityShanghaiChina
| | - Baiyong Shen
- Department of General SurgeryPancreatic Disease Center, Ruijin Hospital Shanghai Jiaotong University School of MedicineShanghaiChina
- Research Institute of Pancreatic DiseaseShanghai Jiaotong University School of MedicineShanghaiChina
- State Key Laboratory of Oncogenes and Related GenesShanghai Jiaotong UniversityShanghaiChina
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12
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Li J, Lin J, Ji Y, Wang X, Fu D, Wang W, Shen B. A novel pyroptosis-associated lncRNA LINC01133 promotes pancreatic adenocarcinoma development via miR-30b-5p/SIRT1 axis. Cell Oncol (Dordr) 2023; 46:1381-1398. [PMID: 37138146 PMCID: PMC10618383 DOI: 10.1007/s13402-023-00818-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/16/2023] [Indexed: 05/05/2023] Open
Abstract
PURPOSE Pancreatic adenocarcinoma (PAAD) remains a highly aggressive gastrointestinal malignancy with a dismal prognosis. Pyroptosis has a key role in tumor development. Long noncoding RNAs (lncRNAs) are involved in tumorigenesis and pyroptosis regulation. However, the prognostic potential and function of pyroptosis-related lncRNAs (PRLs) in PAAD remain unclear. We aimed to identify PRLs with promising predictive value for PAAD prognosis and investigate the mechanism by which PRLs affect pyroptosis and PAAD development. METHODS Key genes that regulate pyroptosis were determined from previous studies, and PRLs were identified from lncRNAs shown to be co-expressed in The Cancer Genome Atlas. Cox analysis and the least absolute shrinkage and selection operator (LASSO) regression model was used to establish a prognostic PRL signature. The clinical significance and functional mechanisms of LINC01133 were explored in vitro and in vivo. RESULTS A seven-lncRNA signature was established and the high-risk subgroup exhibited a shorter survival time. With lower immune infiltration abundance, poor immune function, and higher tumor mutational burden (TMB), the high-risk subgroup reflected a more immunosuppressive status with a greater scope for benefiting from immunotherapy. After LINC01133 knockdown, PAAD cells showed lower viability and higher pyroptosis-related gene expression. LINC01133 functioned as a competing endogenous RNA to sequester miR-30b-5p from sponging SIRT1 mRNA to inhibit PAAD pyroptosis. CONCLUSION With significant prognostic value, our PRL signature are involved in the biological processes of PAAD cells and associated with the immune environment. LINC01133 suppresses pyroptosis to promote PAAD development and could serve as a potential target for PAAD treatment.
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Affiliation(s)
- Jingwei Li
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- State Key Laboratory of Oncogenes and Related Genes, Shanghai, China
- Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jiewei Lin
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- State Key Laboratory of Oncogenes and Related Genes, Shanghai, China
- Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yuchen Ji
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- State Key Laboratory of Oncogenes and Related Genes, Shanghai, China
- Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xuelong Wang
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- State Key Laboratory of Oncogenes and Related Genes, Shanghai, China.
- Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.
| | - Da Fu
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- State Key Laboratory of Oncogenes and Related Genes, Shanghai, China.
- Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.
| | - Weishen Wang
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- State Key Laboratory of Oncogenes and Related Genes, Shanghai, China.
- Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.
| | - Baiyong Shen
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- State Key Laboratory of Oncogenes and Related Genes, Shanghai, China.
- Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.
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13
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Zou W, Wu D, Wu Y, Zhou K, Lian Y, Chang G, Feng Y, Liang J, Huang G. Nomogram predicts risk of perineural invasion based on serum biomarkers for pancreatic cancer. BMC Gastroenterol 2023; 23:315. [PMID: 37723476 PMCID: PMC10508025 DOI: 10.1186/s12876-023-02819-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 05/15/2023] [Indexed: 09/20/2023] Open
Abstract
BACKGROUND Pancreatic cancer is a fatal tumor, and the status of perineural invasion (PNI) of pancreatic cancer was positively related to poor prognosis including overall survival and recurrence-free survival. This study aims to develop and validate a predictive model based on serum biomarkers to accurately predict the perineural invasion. MATERIALS AND METHODS The patients from No.924 Hospital of PLA Joint Logistic Support Force were included. The predictive model was developed in the training cohort using logistic regression analysis, and then tested in the validation cohort. The area under curve (AUC), calibration curves and decision curve analysis were used to validate the predictive accuracy and clinical benefits of nomogram. RESULTS A nomogram was developed using preoperative total bilirubin, preoperative blood glucose, preoperative CA19-9. It achieved good AUC values of 0.753 and 0.737 in predicting PNI in training and validation cohorts, respectively. Calibration curves showed nomogram had good uniformity of the practical probability of PNI. Decision curve analyses revealed that the nomogram provided higher diagnostic accuracy and superior net benefit compared to single indicators. CONCLUSION The present study constructed and validate a novel nomogram predicted the PNI of resectable PHAC patients with high stability and accuracy. Besides, it could better screen high-risk probability of PNI in these patients, and optimize treatment decision-making.
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Affiliation(s)
- Wenbo Zou
- Department of General Surgery, No.924 Hospital of PLA Joint Logistic Support Force, Guilin, 541002, China
| | - Dingguo Wu
- Department of General Surgery, No.924 Hospital of PLA Joint Logistic Support Force, Guilin, 541002, China
| | - Yunyang Wu
- Department of General Surgery, No.924 Hospital of PLA Joint Logistic Support Force, Guilin, 541002, China
| | - Kuiping Zhou
- Department of General Surgery, No.924 Hospital of PLA Joint Logistic Support Force, Guilin, 541002, China
| | - Yuanshu Lian
- Department of General Surgery, No.924 Hospital of PLA Joint Logistic Support Force, Guilin, 541002, China
| | - Gengyun Chang
- Department of General Surgery, No.924 Hospital of PLA Joint Logistic Support Force, Guilin, 541002, China
| | - Yuze Feng
- Department of General Surgery, No.924 Hospital of PLA Joint Logistic Support Force, Guilin, 541002, China
| | - Jifeng Liang
- Department of General Surgery, No.924 Hospital of PLA Joint Logistic Support Force, Guilin, 541002, China
| | - Gao Huang
- Department of General Surgery, No.924 Hospital of PLA Joint Logistic Support Force, Guilin, 541002, China.
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Liu D, Chen J, Zhang Y, Dai Y, Yao X. Magnetic resonance elastography-derived stiffness: potential imaging biomarker for differentiation of benign and malignant pancreatic masses. Abdom Radiol (NY) 2023; 48:2604-2614. [PMID: 37237155 DOI: 10.1007/s00261-023-03956-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 05/06/2023] [Accepted: 05/08/2023] [Indexed: 05/28/2023]
Abstract
OBJECTIVE This study sought to determine the diagnostic performance of magnetic resonance elastography (MRE) for pancreatic solid masses, compared with diffusion-weighted imaging (DWI) and serum CA19-9, to establish a threshold for differentiating between pancreatic ductal adenocarcinoma (PDAC) and benign tumors in pancreas. MATERIALS AND METHODS Between July 2021 to January 2023, 75 adult patients confirmed with pancreatic solid tumors were enrolled in this prospective and consecutive study. All patients underwent MRE and DWI examinations that were both performed with a spin echo-EPI sequence. Stiffness maps and apparent diffusion coefficient (ADC) maps were generated, with MRE-derived mass stiffness and stiffness ratio (computing as the ratio of mass stiffness to the parenchyma stiffness) and DWI-derived ADC values obtained by placing regions of interest over the focal tumors on stiffness and ADC maps. Further analysis of comparing diagnostic performances was assessed by calculating the area under ROC curves. RESULTS PDAC had significantly higher tumor stiffness [3.795 (2.879-4.438) kPa vs. 2.359 (2.01-3.507) kPa, P = 0.0003], stiffness ratio [1.939 (1.562-2.511) vs. 1.187 (1.031-1.453), P < 0.0001] and serum CA19-9 level [276 (31.73-1055) vs. 10.45 (7.825-14.15), P < 0.0001] than other pancreatic masses. Mass stiffness, stiffness ratio and serum CA19-9 showed good diagnostic performance for differentiation with AUC of 0.7895, 0.8392 and 0.9136 respectively. The sensitivity/specificity/positive predictive value/negative predictive value for differentiating malignant from benign pancreatic tumors with mass stiffness (cutoff, > 2.8211 kPa) and stiffness ratio (cutoff, > 1.5117) were 78.4/66.7/82.9/60% and 77.8/83.3/90.3/65.2% respectively. The combined performance of Mass stiffness, stiffness ratio and serum CA19-9 got an AUC of 0.9758. CONCLUSION MRE holds excellent clinical potential in discriminating pancreatic ductal adenocarcinoma from other pancreatic solid masses according to their mechanical properties.
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Affiliation(s)
- Dingxia Liu
- Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China
- Department of Radiology, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Jiejun Chen
- Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China
- Department of Radiology, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Yunfei Zhang
- Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China
- MR Collaboration, Central Research Institute, United Imaging Healthcare, Shanghai, China
| | - Yongming Dai
- MR Collaboration, Central Research Institute, United Imaging Healthcare, Shanghai, China
| | - Xiuzhong Yao
- Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China.
- Department of Radiology, Zhongshan Hospital of Fudan University, Shanghai, China.
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Janga LSN, Sambe HG, Yasir M, Man RK, Gogikar A, Nanda A, Mohammed L. Holistic Understanding of the Role of Carbohydrate Antigen 19-9 in Pancreatic Cancer Screening, Early Diagnosis, and Prognosis: A Systematic Review. Cureus 2023; 15:e44382. [PMID: 37671217 PMCID: PMC10476147 DOI: 10.7759/cureus.44382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Accepted: 08/30/2023] [Indexed: 09/07/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a significant challenge due to its silent progression and well-advanced, unresectable, complicated presentation. Detecting this disease early on is crucial, and researchers have been investigating various potential biological markers, such as carbohydrate antigen 19-9 (CA 19-9), hoping to find indicators that can aid in its early detection. The primary focus of this review is on the diagnostic usefulness of CA 19-9 in detecting pancreatic cancer (PC) in the beginning stage and its usefulness in predicting progression. The database search of articles from PubMed, PMC, the Cochrane Library, and Google Scholar identified 227 articles published from 2013 to 2023. The keyword mix used in the search technique included terms like "CA 19-9," "pancreatic cancer," "diagnosis," and "early detection." This study provides evidence of CA 19-9's ability in detecting PDAC in the pre-diagnostic stage. But since the outcomes were inconsistent among the included trials, further analysis is required to develop standardized diagnostic criteria and methodologies. Furthermore, because of the variability of the study, it is not easy to make firm conclusions on CA 19-9's sensitivity as well as specificity in the first stage of pancreatic neoplasm. This in-depth overview of the available literature provides new insights into using CA 19-9 as a biological marker for detecting undiagnosed PC before progressing into the advanced stage, and was proven beneficial. However, this has to be shown in broader research with adequate sample size. Although it shows promise as a diagnostic tool, further study is required to confirm these findings.
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Affiliation(s)
| | - Hembashima G Sambe
- Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Mohamed Yasir
- Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Ruzhual K Man
- Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Amaresh Gogikar
- Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Ankita Nanda
- Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Lubna Mohammed
- Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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Song Y, Yuan M, Wang G. Update value and clinical application of MUC16 (cancer antigen 125). Expert Opin Ther Targets 2023; 27:745-756. [PMID: 37584221 DOI: 10.1080/14728222.2023.2248376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 06/25/2023] [Accepted: 08/10/2023] [Indexed: 08/17/2023]
Abstract
INTRODUCTION The largest transmembrane mucin, mucin 16 (MUC16), contains abundant glycosylation sites on the molecular surface, allowing it to participate in various molecular pathways. When cells lose polarity and become cancerous, MUC16 is overexpressed, and more of the extracellular region (cancer antigen [CA]125) is released into serum and possibly, promote the development of diseases. Thus, MUC16 plays an indispensable role in clinical research and application. AREAS COVERED This review summarizes the update proposed role of MUC16 in carcinogenesis and metastasis. Most importantly, we prospect its potential value in targeted therapy after screening 1226 articles published within the last 10 years from PubMed. Two reviewers screened each record and each report retrieved independently. We have summarized the progress of MUC16/CA125 in basic research and clinical application, and predicted its possible future development directions. EXPERT OPINION As an important noninvasive co-factor in the diagnosis of gynecological diseases, MUC16 has been used for a long time, especially in the diagnosis and treatment of ovarian cancer. The overexpression of MUC16 plays a very obvious role in regulating inflammatory response, supporting immune suppression, and promoting the proliferation, division, and metastasis of cancer cells. In the next 20 years, there will be a luxuriant clinical application of MUC16 as a target for immune monitoring and immunotherapy.
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Affiliation(s)
- Yaan Song
- Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- Gynecology Laboratory, Shandong Provincial Hospital, Jinan, Shandong, China
| | - Ming Yuan
- Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Gynecology Laboratory, Shandong Provincial Hospital, Jinan, Shandong, China
| | - Guoyun Wang
- Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Gynecology Laboratory, Shandong Provincial Hospital, Jinan, Shandong, China
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Gong Y, Song L, Ou L, Lu YY, Huang X, Zeng Q. Diagnostic and Prognostic Performance of MicroRNA-25, Carbohydrate Antigen 19-9, Carcinoembryonic Antigen, and Carbohydrate Antigen 125 in Pancreatic Ductal Adenocarcinoma. IRANIAN JOURNAL OF MEDICAL SCIENCES 2023; 48:401-413. [PMID: 37456201 PMCID: PMC10349153 DOI: 10.30476/ijms.2022.95583.2705] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 09/04/2022] [Accepted: 09/26/2022] [Indexed: 07/18/2023]
Abstract
Background Pancreatic cancer is a malignancy with high mortality due to the difficulties in early detection. We investigated and compared the diagnostic and prognostic performance of several blood biomarkers, including microRNA-25 (miR-25), carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and carbohydrate antigen 125 (CA125). Methods A retrospective study was conducted at the Chinese People's Liberation Army General Hospital from May 2014 to September 2018. Serum specimens were collected, and miR-25 expression levels were measured using real-time quantitative polymerase chain reaction. Serum CA19-9, CEA, and CA125 levels were measured using enzyme-linked immunosorbent assay (ELISA). Statistical analyses including nonparametric test, receiver operator characteristic (ROC) curves, Kaplan-Meier analysis, and subsequent log-rank test were performed with PRISM 5.0 software. Univariate and multivariate analyses were performed with the R software. P<0.05 was considered statistically significant. Results A total of 250 individuals were recruited, including 75 with pancreatic ductal adenocarcinoma (PDAC), 75 with benign lesions, and 100 healthy controls. miR-25, CA19-9, CEA, and CA125 exhibited an area under the curve (AUC) of 0.88, 0.91, 0.81, and 0.76 with a sensitivity of 78.7%, 74.7%, 37.3%, and 35.7% and specificity of 91.5%, 97.0%, 98.2%, and 98.3%, respectively. The combination of miR-25 and CA19-9 further increased the sensitivity to 93.3% with a specificity of 88.5%. Stage-dependent sensitivity was observed with CA19-9, CEA, and CA125. miR-25 levels significantly stratified the prognosis by median level (4,989.97 copies/mL). CA19-9, CEA, and CA125 levels significantly stratified the prognosis by median levels. Univariate and subsequent multivariate analyses identified tumor (T) stage, CA19-9, and CA125 as independent risk factors for PDAC prognosis. Conclusion The combination of miR-25 and CA19-9 significantly enhanced the detection sensitivity of PDAC. T stage, CA19-9, and CA125 levels were independent risk factors for PDAC prognosis.
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Affiliation(s)
- Yan Gong
- Health Management Institute, The Second Medical Center and National Clinical Research Center for Geriatric Disease, Chinese PLA General Hospital, Beijing, China
| | - Lele Song
- Division of Cancer Early Screening, Genetron Health (Beijing) Technology Co. Ltd., Beijing, China
| | - Lei Ou
- Health Management Institute, The Second Medical Center and National Clinical Research Center for Geriatric Disease, Chinese PLA General Hospital, Beijing, China
| | - You-Yong Lu
- Laboratory of Molecular Oncology, School of Oncology, Peking University, Beijing Cancer Hospital and Institute, Beijing, China
| | - Xianyong Huang
- Health Management Institute, The Second Medical Center and National Clinical Research Center for Geriatric Disease, Chinese PLA General Hospital, Beijing, China
| | - Qiang Zeng
- Health Management Institute, The Second Medical Center and National Clinical Research Center for Geriatric Disease, Chinese PLA General Hospital, Beijing, China
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Guo Y, Wu Z, Cen K, Bai Y, Dai Y, Mai Y, Hong K, Qu L. Establishment and validation of a ubiquitination-related gene signature associated with prognosis in pancreatic duct adenocarcinoma. Front Immunol 2023; 14:1171811. [PMID: 37359528 PMCID: PMC10289160 DOI: 10.3389/fimmu.2023.1171811] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 05/26/2023] [Indexed: 06/28/2023] Open
Abstract
Background Patients with pancreatic duct adenocarcinoma (PDAC) have varied prognoses that depend on numerous variables. However, additional research is required to uncover the latent impact of ubiquitination-related genes (URGs) on determining PDAC patients' prognoses. Methods The URGs clusters were discovered via consensus clustering, and the prognostic differentially expressed genes (DEGs) across clusters were utilized to develop a signature using a least absolute shrinkage and selection operator (LASSO) regression analysis of data from TCGA-PAAD. Verification analyses were conducted across TCGA-PAAD, GSE57495 and ICGC-PACA-AU to show the robustness of the signature. RT-qPCR was used to verify the expression of risk genes. Lastly, we formulated a nomogram to improve the clinical efficacy of our predictive tool. Results The URGs signature, comprised of three genes, was developed and was shown to be highly correlated with the prognoses of PAAD patients. The nomogram was established by combining the URGs signature with clinicopathological characteristics. We discovered that the URGs signature was remarkably superior than other individual predictors (age, grade, T stage, et al). Also, the immune microenvironment analysis indicated that ESTIMATEscore, ImmuneScores, and StromalScores were elevated in the low-risk group. The immune cells that infiltrated the tissues were different between the two groups, as did the expression of immune-related genes. Conclusion The URGs signature could act as the biomarker of prognosis and selecting appropriate therapeutic drugs for PDAC patients.
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Affiliation(s)
- Yangyang Guo
- Department of General Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, China
- Department of Emergency, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, China
| | - Zhixuan Wu
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Kenan Cen
- Department of General Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, China
| | - Yongheng Bai
- National Key Clinical Specialty (General Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Ying Dai
- Department of General Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, China
| | - Yifeng Mai
- Department of General Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, China
| | - Kai Hong
- Department of General Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, China
| | - Liangchen Qu
- Department of Emergency, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, China
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Yang Y, Li G, Zhang Y, Cui Y, Liu J. Protein Induced by Vitamin K Absence II: A Potential Biomarker to Differentiate Pancreatic Ductal Adenocarcinoma from Pancreatic Benign Lesions and Predict Vascular Invasion. J Clin Med 2023; 12:jcm12082769. [PMID: 37109105 PMCID: PMC10147026 DOI: 10.3390/jcm12082769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 03/16/2023] [Accepted: 04/06/2023] [Indexed: 04/29/2023] Open
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant gastrointestinal tumor with a poor prognosis. Serum biomarker carbohydrate antigen 19-9 (CA19-9) was the only well-established biomarker for PDAC with inadequate efficacy. This present study aimed to determine the ability of PIVKA-II to discriminate PDAC from pancreatic benign lesions and predict vascular invasion preoperatively. METHODS Patients who underwent pancreatic surgery from 2017 to 2020 were enrolled. We examined the differential diagnostic ability of protein induced by vitamin K absence II (PIVKA-II), CA19-9, and their combination and 138 with PDAC evaluated the predictive value of PIVKA-II for vascular invasion in PDAC. METHODS A total of 138 patients with PDAC and 90 patients with pancreatic benign lesions who underwent pancreatic surgery from 2017 to 2020 were enrolled. The clinicopathological characteristics were recorded. RESULTS There was a significant difference in levels of serum PIVKA-II between PDAC patients and patients with pancreatic benign lesions (p < 0.001). When the cut-off value was set to 28.9 mAU/mL according to the ROCs, the AUC, sensitivity, and specificity of PIVKA-II were 0.787, 68.1%, and 83.3%, respectively. The combined PIVKA-II and carbohydrate antigen 19-9 (CA19-9) enhanced the diagnostic accuracy, and the AUC, sensitivity, and specificity were 0.945, 87.7%, and 94.4%, respectively. PIVKA-II > 36.4 mAU/mL were independent predictive factors of vascular invasion in PDAC (p < 0.001). CONCLUSION PIVKA-II was a potential diagnostic biomarker to differentiate PDAC from pancreatic benign lesions. PIVKA-II was complementary to CA19-9, and the combination enhanced the differential diagnostic performance. PIVKA-II > 36.4 mAU/mL was an independent predictive factor of vascular invasion in PDAC.
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Affiliation(s)
- Yang Yang
- Department of Surgery, Tianjin Nankai Hospital, Nankai Clinical School of Medicine, Tianjin Medical University, Tianjin 300070, China
| | - Guangbing Li
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China
| | - Yu Zhang
- Department of Surgery, Tianjin Nankai Hospital, Nankai Clinical School of Medicine, Tianjin Medical University, Tianjin 300070, China
| | - Yunfeng Cui
- Department of Surgery, Tianjin Nankai Hospital, Nankai Clinical School of Medicine, Tianjin Medical University, Tianjin 300070, China
| | - Jun Liu
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China
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Caba O, Diéguez-Castillo C, Martínez-Galán J, González-Cebrián I, Jiménez-Luna C. Serum biomarkers for the differentiation of autoimmune pancreatitis from pancreatic ductal adenocarcinoma. World J Gastrointest Oncol 2023; 15:268-275. [PMID: 36908319 PMCID: PMC9994052 DOI: 10.4251/wjgo.v15.i2.268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 11/29/2022] [Accepted: 01/17/2023] [Indexed: 02/14/2023] Open
Abstract
Autoimmune pancreatitis (AIP), a chronic inflammation caused by the immune system attacking the pancreas, usually presents imaging and clinical features that overlap with those of pancreatic ductal adenocarcinoma (PDAC). Serum biomarkers, substances that quantitatively change in sera during disease development, are a promising non-invasive tool with high utility for differentiating between these diseases. In this way, the presence of AIP is currently suspected when serum concentrations of immunoglobulin G4 (IgG4) antibody are elevated. However, this approach has some drawbacks. Notably, IgG4 antibody concentrations are also elevated in sera from some patients with PDAC. This review focuses on the most recent and relevant serum biomarkers proposed to differentiate between AIP and PDAC, evaluating the usefulness of immunoglobulins, autoantibodies, chemokines, and cytokines. The proposed serum biomarkers have proven useful, although most studies had a small sample size, did not examine their presence in patients with PDAC, or did not test them in humans. In addition, current evidence suggests that a single serum biomarker is unlikely to accurately differentiate these diseases and that a set of biomarkers will be needed to achieve adequate specificity and sensitivity, either alone or in combination with clinical data and/or radiological images.
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Affiliation(s)
- Octavio Caba
- Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Granada 18016, Spain
- Biosanitary Institute of Granada (ibs.GRANADA), 18014 Granada, Spain
| | | | - Joaquina Martínez-Galán
- Department of Medical Oncology, Virgen de las Nieves University Hospital, Granada 18014, Spain. Biosanitary Institute of Granada (ibs.GRANADA), 18014 Granada, Spain
| | | | - Cristina Jiménez-Luna
- Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Granada 18016, Spain
- Biosanitary Institute of Granada (ibs.GRANADA), 18014 Granada, Spain
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Identification and validation of volatile organic compounds in bile for differential diagnosis of perihilar cholangiocarcinoma. Clin Chim Acta 2023; 541:117235. [PMID: 36716909 DOI: 10.1016/j.cca.2023.117235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 01/12/2023] [Accepted: 01/24/2023] [Indexed: 01/29/2023]
Abstract
Early and differential diagnosis of perihilar cholangiocarcinoma (PHCCA) is highly challenging. This study aimed to evaluate whether volatile organic compounds (VOCs) in bile samples could be emerging diagnostic biomarkers for PHCCA. We collected 200 bile samples from patients with PHCCA and benign biliary diseases (BBD), including a 140-patient training cohort and an 60-patient test cohort. Gas chromatography-ion mobility spectrometry (GC-IMS) was used for VOCs detection. The predictive models were constructed using machine learning algorithms. Our analysis detected 19 VOC substances using GC-IMS in the bile samples and resulted in the identification of three new VOCs, 2-methoxyfuran, propyl isovalerate, and diethyl malonate that were found in bile. Unsupervised hierarchical clustering analysis supported that VOCs detected in the bile could distinguish PHCCA from BBD. Twelve VOCs defined according to 32 signal peaks had significant statistical significance between BBD and PHCCA, including four up-regulated VOCs in PHCCA, such as 2-ethyl-1-hexanol, propyl isovalerate, cyclohexanone, and acetophenone, while the rest eight VOCs were down-regulated. ROC curve analysis revealed that machine learning models based on VOCs could help diagnosing PHCCA. Among them, SVM provided the highest AUC of 0·966, with a sensitivity and specificity of 93·1% and 100%, respectively. The diagnostic model based on different VOC spectra could be a feasible method for the differential diagnosis of PHCCA.
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Wu J, Zhang Q, Kang L, Wu X, Li D, Wang Y, Huang Y, Xue J. Detection of carcinoembryonic antigens using a wavy gold-silver alloy nanoplate enhanced surface plasmon resonance imaging biosensor. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2022; 14:4713-4720. [PMID: 36342011 DOI: 10.1039/d2ay01523d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Carcinoembryonic antigen (CEA) is regarded as a promising broad spectrum tumor biomarker for clinical diagnosis, progression, and prognosis. Surface plasmon resonance imaging (SPRi) was considered as one of the powerful tools for immunoassay with advantages of label-free, real-time detection with high-throughput. Herein, wavy gold-silver alloy nanoplates functionalized with anti-CEA antibodies providing high protein loading capacity and high mass are used as signal enhancers for CEA detection through SPRi sandwich assay. The present method exhibits a dynamic range for CEA determination from 0.1 to 312.5 ng mL-1 and a detection limit of 0.55 ng mL-1, well below normal physiological levels. This biosensing approach demonstrates the advantages of wavy gold-silver alloy nanoplates compared to conventional gold nanoparticles as a signal amplifier to enhance the SPRi signal, which is expected to become a new prospect for detection of cancer markers in biomedical research and clinical diagnosis.
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Affiliation(s)
- Jiangling Wu
- Department of Clinical Laboratory, Medical Sciences Research Center, University-Town Hospital of Chongqing Medical University, Chongqing, 401331, China.
| | - Qiongyuan Zhang
- Department of Clinical Laboratory, Medical Sciences Research Center, University-Town Hospital of Chongqing Medical University, Chongqing, 401331, China.
| | - Lina Kang
- Department of Clinical Laboratory, Medical Sciences Research Center, University-Town Hospital of Chongqing Medical University, Chongqing, 401331, China.
| | - Xiaotian Wu
- Department of Clinical Laboratory, Medical Sciences Research Center, University-Town Hospital of Chongqing Medical University, Chongqing, 401331, China.
| | - Daikun Li
- Department of Clinical Laboratory, Medical Sciences Research Center, University-Town Hospital of Chongqing Medical University, Chongqing, 401331, China.
| | - Yi Wang
- Chongqing Key Laboratory of Green Synthesis and Applications, College of Chemistry, Chongqing Normal University, Chongqing 401331, China
| | - Yu Huang
- Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400714, China.
| | - Jianjiang Xue
- Department of Clinical Laboratory, Medical Sciences Research Center, University-Town Hospital of Chongqing Medical University, Chongqing, 401331, China.
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Early Assessment of Chemoradiotherapy Response for Locally Advanced Pancreatic Ductal Adenocarcinoma by Dynamic Contrast-Enhanced Ultrasound. Diagnostics (Basel) 2022; 12:diagnostics12112662. [PMID: 36359506 PMCID: PMC9689529 DOI: 10.3390/diagnostics12112662] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 10/27/2022] [Accepted: 10/28/2022] [Indexed: 11/06/2022] Open
Abstract
Objective: To evaluate the value of dynamic contrast-enhanced ultrasound (DCE-US) and quantitative parameters in early prediction of tumor response to chemoradiotherapy (CRT) in patients with locally advanced pancreatic ductal adenocarcinoma (LAPC). Patients and Methods: In this prospective study, patients with biopsy-proved and histopathologically proved LAPC who underwent regular CRT were recruited. DCE-US evaluations were performed before and four months after CRT. SonoVue-enhanced contrast-enhanced ultrasound (CEUS) was performed by an ultrasound system (ACUSON Sequoia; Siemens Medical Solutions, USA) equipped with a 5C1 MHz convex array transducer. Time−intensity curves were created by VueBox software (Bracco, Italy), and various DCE-US quantitative parameters were obtained. Taking Response Evaluation Criteria in Solid Tumors (RECIST) based on computed tomography (CT) or magnetic resonance imaging (MRI) as the gold standard, DCE-US parameters were compared between the treatment responder group (RG) and non-responder group (NRG). The correlation between the DCE-US parameters and the serum carbohydrate antigen 19-9 (CA 19-9) level was also analyzed. Results: Finally, 21 LAPC patients (mean age 59.3 ± 7.2 years) were included. In comparing the RG (n = 18) and NRG (n = 3), no significant change could be found among the mean size of the lesions (31.2 ± 8.1 mm vs. 27.2 ± 8.3 mm, p = 0.135). In comparing the TICs between the two groups, the LAPC lesions in the RG took a longer time to reach peak enhancement and to wash out. Among all the DCE-US parameters, RT (rise time), WiAUC (wash-in area under the curve), WoAUC (wash-out area under the curve) and WiWoAUC (wash-in and wash-out area under the curve) decreased significantly after CRT in the RG (p < 0.05). The RT ratio, WiAUC ratio, WoAUC ratio and WiWoAUC ratio were closely correlated with the change in serum CA 19-9 level in the RG (p < 0.05). Conclusion: DCE-US might be a potential imaging method for non-invasive follow-up for early response in LAPC patients treated by CRT.
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Bagias G, Kanavidis P, Vailas M, Despotidis M, Sotiropoulou M, Katsaros I, Maroulis I, Filippou D, Schizas D. Surgical management of familial pancreatic cancer: a systematic review of the literature. ANZ J Surg 2022; 92:2816-2821. [PMID: 35758214 DOI: 10.1111/ans.17834] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 04/30/2022] [Accepted: 05/19/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is the third most common cause of cancer-related mortality. The fact that the vast majority of patients with PDAC are diagnosed at an advanced stage highlights the need of early diagnosis. As hereditary factors are associated with approximately 5% of all PDAC cases, a screening programme to these high-risk individuals (HRI) has been proposed. The aim of screening methods is to identify selected group of patients with morphological abnormalities at an early stage, in order to be treated promptly. In this study, we evaluate the surgical outcomes and the appropriateness of pancreatic resection in HRIs who were selected for screening. METHODS A systematic literature search of the PubMed, Embase, and Cochrane databases was performed. The clinicopathological features were recorded and evaluated. RESULTS Six studies were selected for data collection. A total number of 77 patients were identified. Twenty-one patients had a germline mutation, with CDKN2A being the most prominent one (15.6%). Distal pancreatectomy was the most common surgical procedure (42.8%), followed by pancreaticoduodenectomy (33.8%). The mean disease-free survival was 23.6 months and tumour recurrence occurred in 9 patients (11.7%). Disease-specific mortality was 17.8%, while overall mortality was 19.5%. The most frequently reported postoperative diagnosis was PDAC (28 cases, 38.9%), followed by IPMN (23 cases, 31.9%), whereas high-grade PanIN lesions were found in 13 patients (18.1%). CONCLUSION High-risk individuals for pancreatic cancer, who are eventually operated may have a relatively uneventful postoperative course, however the oncological outcomes are comparable to the general population.
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Affiliation(s)
- George Bagias
- Third Department of Surgery, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - Prodromos Kanavidis
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Michail Vailas
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Markos Despotidis
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Maria Sotiropoulou
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Ioannis Katsaros
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Ioannis Maroulis
- Department of Surgery, University of Patras Medical School, Patras, Greece
| | - Dimitrios Filippou
- Department of Anatomy and Surgical Anatomy, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitrios Schizas
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
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Egea J, Salleron J, Gourgou S, Ayav A, Laurent V, Juzyna B, Harlé A, Conroy T, Lambert A. Development of a Clinical-Biological Model to Assess Tumor Progression in Metastatic Pancreatic Cancer: Post Hoc Analysis of the PRODIGE4/ACCORD11 Trial. Cancers (Basel) 2022; 14:cancers14205068. [PMID: 36291851 PMCID: PMC9599967 DOI: 10.3390/cancers14205068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 10/03/2022] [Accepted: 10/11/2022] [Indexed: 11/21/2022] Open
Abstract
Background: The follow-up of pancreatic cancer (PC) is based on computed tomography (CT) assessment; however, there is no consensus on the use of clinical and biological criteria in tumor progression. We aimed to establish a clinical−biological model to highlight the progression of metastatic PC during first-line treatment. Methods: The patients treated with first-line chemotherapy in the phase 2/3 PRODIGE4/ACCORD11 clinical trial were evaluated retrospectively. Clinical and biological markers were evaluated at the time of CT scans and during treatment to determine tumor progression. Results: In total, 196 patients were analyzed, with 355 available tumor assessments. The clinical and biological factors associated with tumor progression in multivariate analysis included gemcitabine, global health status ≤ 33 (OR = 3.38, 95%CI [1.15; 9.91], p = 0.028), quality of life score between 34 and 66 (OR = 2.65, 95%CI [1.06; 6.59], p = 0.037), carcinoembryonic antigen (CEA) ≥ 3 times the standard value without any increase in the CEA level from inclusion (OR = 2.22, 95%CI [1.01; 4.89], p = 0.048) and with an increase in the CEA level from inclusion (OR = 6.56, 95%CI [2.73; 15.78], p < 0.001), and an increase in the carbohydrate antigen 19-9 level from inclusion (OR = 2.59, 95%CI [1.25; 5.36], p = 0.016). Conclusions: The self-assessment of patients’ general health status alongside tumor markers is an interesting approach to the diagnosis of the tumor progression of metastatic pancreatic cancer patients during first-line treatment.
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Affiliation(s)
- Julie Egea
- Department of Medical Oncology, Institut de Cancérologie de Lorraine, 54500 Vandœuvre-lès-Nancy, France
| | - Julia Salleron
- Biostatistic Unit, Institut de Cancérologie de Lorraine, 54500 Vandœuvre-lès-Nancy, France
| | - Sophie Gourgou
- Biometrics Unit, Institut régional du Cancer Montpellier Val d’Aurelle, Université de Montpellier, 34298 Montpellier, France
| | - Ahmet Ayav
- Department of Gastrointestinal Surgery, Centre Hospitalier Universitaire de Nancy, 54500 Vandœuvre-lès-Nancy, France
| | - Valérie Laurent
- Department of Radiology, Centre Hospitalier Universitaire de Nancy, 54500 Vandœuvre-lès-Nancy, France
| | - Béata Juzyna
- UNICANCER Research and Development Team, 75654 Paris, France
| | - Alexandre Harlé
- Department of Biopathology, Institut de Cancérologie de Lorraine, 54500 Vandœuvre-lès-Nancy, France
| | - Thierry Conroy
- Department of Medical Oncology, Institut de Cancérologie de Lorraine, 54500 Vandœuvre-lès-Nancy, France
| | - Aurélien Lambert
- Department of Medical Oncology, Institut de Cancérologie de Lorraine, 54500 Vandœuvre-lès-Nancy, France
- Correspondence: ; Tel.: +33-(0)-3-83-59-85-64
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Ji L, Zhang W, Hao S, Wang Z, Ding T, Zhang G. Percutaneous transhepatic cholangial drainage combined with intra-tumoral iodine-125 seeds implantation and chemotherapy for locally progressive pancreatic head cancer with obstructive jaundice. J Contemp Brachytherapy 2022; 14:462-469. [PMID: 36478703 PMCID: PMC9720689 DOI: 10.5114/jcb.2022.121563] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Accepted: 10/13/2022] [Indexed: 11/27/2024] Open
Abstract
PURPOSE To investigate the clinical efficacy of percutaneous transhepatic cholangial drainage (PTCD) combined with intra-tumoral iodine-125 (125I) particle implantation and chemotherapy in the treatment of locally advanced pancreatic head cancer (LAPHC) with obstructive jaundice. MATERIAL AND METHODS Twenty-one patients with LAPHC with obstructive jaundice were selected, and routine examination before surgery to determine location of obstruction and degree of bile duct dilatation was performed. All 21 patients underwent PTCD first, and usual examinations, including liver and kidney function, were re-examined after operation. When the liver function recovered significantly, patients were treated with seed implantation and systemic chemotherapy after surgery. Clinical efficacy and complications of 21 patients were observed, and changes in survival time and serum level of tumor markers were analyzed. RESULTS After combined treatment, there were 3 cases of complete response (CR), 12 cases of partial response (PR), 3 cases of stable disease (SD), and 3 cases of progressive disease (PD) in 21 patients. The overall effective rate was 71.43%, and the local control rate was 85.71%. The pain relief was statistically significant one month after treatment, compared with that before treatment (VAS scores: 6.76 ±2.25 vs. 3.25 ±1.92, p < 0.001), and the rate of pain relief was 71.43% (15/21). In all patients, jaundice, abdominal pain, and abdominal distension improved to different degrees after surgery, and the skin pruritus disappeared. Bilirubin and transaminase improved to varying degrees 3 days, 1 week, and 4 weeks after treatment (p < 0.05). Cancer antigen 199 (CA-199), carcinoembryonic antigen (CEA), and cancer antigen 125 (CA-125) after combination therapy, achieved statistically significant differences (t = 9.525, 10.378, 3.262, respectively, p < 0.05). The overall survival time of 21 patients was 11.6 months, ranging from 3.9 to 22.6 months. CONCLUSIONS For LAPHC patients with obstructive jaundice, PTCD combined with particle implantation and chemotherapy is clinically effective in improving the quality of life and prolonging survival.
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Affiliation(s)
- Liqiu Ji
- General Hospital of Northern Theater Command, Liaoning, China
| | - Wenwen Zhang
- General Hospital of Northern Theater Command, Liaoning, China
| | - Shanhu Hao
- General Hospital of Northern Theater Command, Liaoning, China
| | - Zhiguo Wang
- General Hospital of Northern Theater Command, Liaoning, China
| | - Tingting Ding
- General Hospital of Northern Theater Command, Liaoning, China
| | - Guoxu Zhang
- General Hospital of Northern Theater Command, Liaoning, China
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Chen H, Zhang J, Sun X, Wang Y, Qian Y. Mitophagy-mediated molecular subtypes depict the hallmarks of the tumour metabolism and guide precision chemotherapy in pancreatic adenocarcinoma. Front Cell Dev Biol 2022; 10:901207. [PMID: 35938160 PMCID: PMC9353335 DOI: 10.3389/fcell.2022.901207] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 06/30/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Mitophagy is closely related to cancer initiation and progression. However, heterogeneity with reference to mitophagy remains unexplored in pancreatic adenocarcinoma (PAAD). Materials and methods: We used Reactome database to download the mitophagy-related, glycolysis-related and cholesterol biosynthesis-related signaling pathways. Unsupervised clustering using the “ConsensusClusterPlus” R package was performed to identify molecular subtypes related to mitophagy and metabolism. Prognosis-related mitophagy regulators were identified by univariate Cox regression analysis. Receiver operating characteristics (ROC) and Kaplan-Meier (K-M) survival analyses were used to assess the diagnostic and prognostic role of the hub genes and prognosis risk model. Weighted gene co-expression network analysis (WGCNA) was utilized for screening the mitophagy subtype-related hub genes. Metascape was utilized to carry out functional enrichment analysis. The “glmnet” R package was utilised for LASSO, and the “e1071” R package was utilised for SVM. Chemotherapeutic drug sensitivity was estimated using the R package “pRRophetic” and Genomics of Drug Sensitivity in Cancer (GDSC) database. The nomogram was established by the “rms” R package. Results: Three distinct mitophagy subtypes (low, high and intermediate) of PAAD were identified based on the landscape of mitophagy regulators. The high mitophagy subtype had the worst prognosis, highest mRNA expression-based stemness index scores and most hypoxic environment compared to the other subtypes. Additionally, glycolysis and cholesterol biosynthesis were significantly elevated. Three mitophagy subtype-specific gene signatures (CAST, CCDC6, and ERLIN1) were extracted using WGCNA and machine learning. Moreover, PAAD tumours were insensitive to Erlotinib, Sunitinib and Imatinib in the high mitophagy subtype and high CAST, CCDC6, and ERLIN1 expressed subtypes. Furthermore, CAST, CCDC6, and ERLIN1 affected immune cell infiltration (M1 and CD8Tcm), resulting in the altered prognosis of patients with PAAD. A nomogram was constructed to screen patients with the low mitophagy subtype, which showed a higher sensitivity to chemotherapeutic agents. Conclusion: Based on various bioinformatics tools and databases, the PAAD heterogeneity regarding mitophagy was systematically examined. Three different PAAD subtypes having different outcomes, metabolism patterns and chemosensitivity were observed. Moreover, three novel biomarkers that are closely associated with mitophagy and have the potential to guide individualised treatment regimens in PAAD were obtained.
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Affiliation(s)
- Hao Chen
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Department of Emergency Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Jianlin Zhang
- Department of Emergency Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Xuehu Sun
- Department of Emergency Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yao Wang
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- *Correspondence: Yeben Qian, ; Yao Wang,
| | - Yeben Qian
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- *Correspondence: Yeben Qian, ; Yao Wang,
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28
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Hong L, Xu L, Jin L, Xu K, Tang W, Zhu Y, Qiu X, Wang J. Exosomal circular RNA hsa_circ_0006220, and hsa_circ_0001666 as biomarkers in the diagnosis of pancreatic cancer. J Clin Lab Anal 2022; 36:e24447. [PMID: 35446993 PMCID: PMC9169197 DOI: 10.1002/jcla.24447] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 04/04/2022] [Accepted: 04/06/2022] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Pancreatic cancer is a highly malignant tumor of the digestive system. OBJECTIVE Exosomal circular RNA can be used as a biomarker for the early diagnosis of pancreatic cancer. METHODS The expression of various differentially expressed circRNAs in pancreatic cancer tissues was analyzed by gene chip, exosome expression was verified by electron microscopy and Western blotting, and the expression of exosomal circRNA in pancreatic cancer cells, tissues, and plasma were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS Compared with healthy controls, hsa_circ_0006220 and hsa_circ_0001666 were highly expressed in exosomes in the plasma of pancreatic cancer patients. The AUC values were 0.7817 for hsa_circ_0006220, 0.8062 for hsa_circ_0001666, and 0.884 for the combined diagnosis. In addition, clinicopathological features revealed that the expression of hsa_circ_0006220 in plasma exosomes from pancreatic cancer patients was associated with CA19-9 levels (p = 0.0001) and lymph node metastasis (p = 0.0005). The expression of hsa_circ_0001666 was correlated with both tumor size (p = 0.0157) and CA19-9 level (p = 0.0001). CONCLUSIONS The high expression of exosomal hsa_circ_0001666 and hsa_circ_0006220 suggests that these can be used as new biomarkers for the diagnosis and treatment of pancreatic cancer.
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Affiliation(s)
- Lu Hong
- Department of RadiologyThe Affiliated Hospital of Medical School of Ningbo UniversityNingboChina
| | - Liu Xu
- Department of RadiologyThe Affiliated Hospital of Medical School of Ningbo UniversityNingboChina
| | - Lufei Jin
- Department of RadiologyThe Affiliated Hospital of Medical School of Ningbo UniversityNingboChina
| | - Kaiwei Xu
- Department of RadiologyThe Affiliated Hospital of Medical School of Ningbo UniversityNingboChina
| | - Weiwei Tang
- Department of RadiologyThe Affiliated Hospital of Medical School of Ningbo UniversityNingboChina
| | - Yuchao Zhu
- Department of RadiologyThe Affiliated Hospital of Medical School of Ningbo UniversityNingboChina
| | - Xuedan Qiu
- Ningbo Medical Center Lihuili Eastern HospitalNingboChina
| | - Jianhua Wang
- Department of RadiologyThe Affiliated Hospital of Medical School of Ningbo UniversityNingboChina
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29
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Benke M, Farkas N, Hegyi P, Tinusz B, Sarlós P, Erőss B, Szemes K, Vörhendi N, Szakács Z, Szücs Á. Preoperative Serum Carbohydrate Antigen 19-9 Levels Cannot Predict the Surgical Resectability of Pancreatic Cancer: A Meta-Analysis. Pathol Oncol Res 2022; 28:1610266. [PMID: 35645620 PMCID: PMC9136945 DOI: 10.3389/pore.2022.1610266] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 04/12/2022] [Indexed: 11/18/2022]
Abstract
Background and Aims: Pancreatic ductal adenocarcinoma has one of the worst prognosis of all malignancies. This investigated the relationship between the preoperative serum carbohydrate antigen 19-9 and surgical resectability. Methods: A systematic search was performed in three databases (MEDLINE, EMBASE, and Web of Science) to compare the surgical resectability of pancreatic ductal adenocarcinoma in patients with high and low preoperative serum carbohydrate antigen 19-9 values. The receiving operating characteristic curves were constructed and the weighted mean differences for preoperative serum carbohydrate antigen 19-9 levels of resectable and unresectable groups of patients were calculated. The PROSPERO registration number is CRD42019132522. Results: Results showed that there was a significant difference in resectability between the low and high carbohydrate antigen 19-9 groups. Six out of the eight studies utilised receiver operating characteristic curves in order to find the cut-off preoperative carbohydrate antigen 19-9 levels marking unresectability. The overall result from the pooled area under curve values from the receiver operating characteristic curves was 0.794 (CI: 0.694-0.893), showing that the preoperative carbohydrate antigen 19-9 level is a "fair" marker of resectability. The result of the pooled weighted mean differences was 964 U/ml (p < 0.001) showing that there is a significant carbohydrate antigen 19-9 difference between the resectable and unresectable groups. Based on the results of the I-squared test, the result was 87.4%, accounting for "considerable" heterogeneity within the population. Conclusion: Carbohydrate antigen 19-9 is not a reliable marker of unresectability, it should not be used on its own in surgical decision-making.
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Affiliation(s)
- Márton Benke
- First Department of Surgery, Semmelweis University, Budapest, Hungary
| | - Nelli Farkas
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Szentágothai Research Centre, University of Pécs, Pécs, Hungary
- Institute of Bioanalysis, Medical School, University of Pécs, Pécs, Hungary
| | - Péter Hegyi
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Division of Gastroenterology, First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary
- First Department of Medicine, University of Szeged, Szeged, Hungary
| | - Benedek Tinusz
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Szentágothai Research Centre, University of Pécs, Pécs, Hungary
| | - Patrícia Sarlós
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Division of Gastroenterology, First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary
- Clinical Medicine Doctoral School, University of Szeged, Szeged, Hungary
| | - Bálint Erőss
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Clinical Medicine Doctoral School, University of Szeged, Szeged, Hungary
| | - Kata Szemes
- Division of Gastroenterology, First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Nóra Vörhendi
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Zsolt Szakács
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Szentágothai Research Centre, University of Pécs, Pécs, Hungary
| | - Ákos Szücs
- First Department of Surgery, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
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Colorectal Cancer Diagnosis: The Obstacles We Face in Determining a Non-Invasive Test and Current Advances in Biomarker Detection. Cancers (Basel) 2022; 14:cancers14081889. [PMID: 35454792 PMCID: PMC9029324 DOI: 10.3390/cancers14081889] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 04/04/2022] [Accepted: 04/06/2022] [Indexed: 02/07/2023] Open
Abstract
Simple Summary Colorectal cancer (CRC) is one of the most common cancers in the western world. CRC originates from precursor adenomatous polyps, which may over time develop into cancer. Endoscopic evaluation remains the gold-standard investigation for the disease. In the absence of molecular tools for early detection, the removal of neoplastic adenomas via polypectomy remains an important measure to prevent dysplastic adenomas from evolving into invasive carcinoma. Colonoscopy is an intrusive procedure that provides an uncomfortable experience for patients. Kits for testing for the presence of blood hemoglobin in the stool are now widely used, and DNA methylation-based detection kits have been approved in the USA for testing the stool and plasma, but few other molecular biomarkers have found their way into medical practice. This review summarizes current trends in the detection and screening of CRC and provides a definitive review of emerging molecular biomarkers for CRC. Abstract Globally, colorectal cancer (CRC) is the third most common cancer, with 1.4 million new cases and over 700,000 deaths per annum. Despite being one of the most common cancers, few molecular approaches to detect CRC exist. Carcinoembryonic antigen (CEA) is a known serum biomarker that is used in CRC for monitoring disease recurrence or response to treatment. However, it can also be raised in multiple benign conditions, thus having no value in early detection or screening for CRC. Molecular biomarkers play an ever-increasing role in the diagnosis, prognosis, and outcome prediction of disease, however, only a limited number of biomarkers are available and none are suitable for early detection and screening of CRC. A PCR-based Epi proColon® blood plasma test for the detection of methylated SEPT9 has been approved by the USFDA for CRC screening in the USA, alongside a stool test for methylated DNA from CRC cells. However, these are reserved for patients who decline traditional screening methods. There remains an urgent need for the development of non-invasive molecular biomarkers that are highly specific and sensitive to CRC and that can be used routinely for early detection and screening. A molecular approach to the discovery of CRC biomarkers focuses on the analysis of the transcriptome of cancer cells to identify differentially expressed genes and proteins. A systematic search of the literature yielded over 100 differentially expressed CRC molecular markers, of which the vast majority are overexpressed in CRC. In terms of function, they largely belong to biological pathways involved in cell division, regulation of gene expression, or cell proliferation, to name a few. This review evaluates the current methods used for CRC screening, current availability of biomarkers, and new advances within the field of biomarker detection for screening and early diagnosis of CRC.
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Winter K, Dzieniecka M, Strzelczyk J, Wągrowska-Danilewicz M, Danilewicz M, Zatorski H, Małecka-Wojciesko E. Hedgehog Signaling Pathway Proteins in Prognosis of Pancreatic Ductal Adenocarcinoma and Its Differentiation From Chronic Pancreatitis. Pancreas 2022; 51:219-227. [PMID: 35584378 DOI: 10.1097/mpa.0000000000002001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES The Hedgehog signaling pathway (Hh) probably plays a role in development and progression of pancreatic ductal adenocarcinoma (PDAC). METHODS In our study, 114 patients (83 with PDAC and 31 with chronic pancreatitis [CP]) after pancreatic surgery were enrolled. The immunoexpression of Sonic hedgehog (Shh), Smoothened (Smo), and Glioblastoma transcription factor 1 (Gli1) and Ki-67 were detected in tissue specimens. RESULTS Mean (standard deviation) immunoexpression of all Hh pathway molecules was significantly higher in PDAC than in CP patients: Shh, 2.24 (0.57) versus 1.17 (0.25) (P < 0.01); Smo, 2.62 (0.34) versus 1.21 (0.23) (P < 0.01); and Gli1, 1.74 (0.74) versus 1.15 (0.72) (P < 0.01). Patients with a lower expression level (z score <0) of Shh and Ki-67 have longer overall survival when compared with z score >0 (15.97 vs 8.53 months [P = 0.0087] and 15.20 vs 5.53 months [P = 0.0004], respectively). In addition, Shh sensitivity in PDAC detection was 84.3%; specificity, 93.5%; positive predictive value, 97.2%; and negative predictive value, 69%. CONCLUSIONS Our results suggest the prognostic role of the Hh pathway in PDAC and a role in the differential diagnosis with CP.
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Affiliation(s)
- Katarzyna Winter
- From the Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland
| | | | | | | | - Marian Danilewicz
- Nephropathology, Division of Morphometry, Medical University of Lodz, Lodz, Poland
| | - Hubert Zatorski
- From the Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland
| | - Ewa Małecka-Wojciesko
- From the Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland
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Mortoglou M, Buha Djordjevic A, Djordjevic V, Collins H, York L, Mani K, Valle E, Wallace D, Uysal-Onganer P. Role of microRNAs in response to cadmium chloride in pancreatic ductal adenocarcinoma. Arch Toxicol 2022; 96:467-485. [PMID: 34905088 PMCID: PMC8837568 DOI: 10.1007/s00204-021-03196-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 11/10/2021] [Indexed: 02/07/2023]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal and aggressive malignancies with a 5-year survival rate less than 9%. Early detection is particularly difficult due to the lack of symptoms even in advanced stages. microRNAs (miRs/miRNAs) are small (~ 18-24 nucleotides), endogenous, non-coding RNAs, which are involved in the pathogenesis of several malignancies including PDAC. Alterations of miR expressions can lead to apoptosis, angiogenesis, and metastasis. The role of environmental pollutants such as cadmium (Cd) in PDAC has been suggested but not fully understood. This study underlines the role of miRs (miR-221, miR-155, miR-126) in response to cadmium chloride (CdCl2) in vitro. Lethal concentration (LC50) values for CdCl2 resulted in a toxicity series of AsPC-1 > HPNE > BxPC-3 > Panc-1 = Panc-10.5. Following the treatment with CdCl2, miR-221 and miR-155 were significantly overexpressed, whereas miR-126 was downregulated. An increase in epithelial-mesenchymal transition (EMT) via the dysregulation of mesenchymal markers such as Wnt-11, E-cadherin, Snail, and Zeb1 was also observed. Hence, this study has provided evidence to suggest that the environmental pollutant Cd can have a significant role in the development of PDAC, suggesting a significant correlation between miRs and Cd exposure during PDAC progression. Further studies are needed to investigate the precise role of miRs in PDAC progression as well as the role of Cd and other environmental pollutants.
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Affiliation(s)
- Maria Mortoglou
- Cancer Research Group, School of Life Sciences, University of Westminster, London, W1W 6UW UK
| | | | | | - Hunter Collins
- College of Medicine and the Department of Pharmacology and Physiology, Oklahoma State University Center for Health Sciences, 1111 West 17th Street, Tulsa, OK 74107-1898 USA
| | - Lauren York
- College of Medicine and the Department of Pharmacology and Physiology, Oklahoma State University Center for Health Sciences, 1111 West 17th Street, Tulsa, OK 74107-1898 USA
| | - Katherine Mani
- College of Medicine and the Department of Pharmacology and Physiology, Oklahoma State University Center for Health Sciences, 1111 West 17th Street, Tulsa, OK 74107-1898 USA
| | - Elizabeth Valle
- College of Medicine and the Department of Pharmacology and Physiology, Oklahoma State University Center for Health Sciences, 1111 West 17th Street, Tulsa, OK 74107-1898 USA
| | - David Wallace
- College of Medicine and the Department of Pharmacology and Physiology, Oklahoma State University Center for Health Sciences, 1111 West 17th Street, Tulsa, OK 74107-1898 USA
| | - Pinar Uysal-Onganer
- Cancer Research Group, School of Life Sciences, University of Westminster, London, W1W 6UW UK
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Xia LY, Tang YN, Zhang J, Dong TY, Zhou RX. Advances in the DNA Nanotechnology for the Cancer Biomarkers Analysis: Attributes and Applications. Semin Cancer Biol 2022; 86:1105-1119. [PMID: 34979273 DOI: 10.1016/j.semcancer.2021.12.012] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Revised: 12/26/2021] [Accepted: 12/29/2021] [Indexed: 02/07/2023]
Abstract
The most commonly used clinical methods are enzyme-linked immunosorbent assay (ELISA) and quantitative PCR (qPCR) in which ELISA was applied for the detection of protein biomarkers and qPCR was especially applied for nucleic acid biomarker analysis. Although these constructed methods have been applied in wide range, they also showed some inherent shortcomings such as low sensitivity, large sample volume and complex operations. At present, many methods have been successfully constructed on the basis of DNA nanotechnology with the merits of high accuracy, rapid and simple operation for cancer biomarkers assay. In this review, we summarized the bioassay strategies based on DNA nanotechnology from the perspective of the analytical attributes for the first time and discussed and the feasibility of the reported strategies for clinical application in the future.
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Affiliation(s)
- Ling-Ying Xia
- Biliary Surgical Department of West China Hospital, Sichuan University, Chengdu, Sichuan 610064, PR China; Analytical & Testing Center, Sichuan University, Chengdu, Sichuan 610064, PR China
| | - Ya-Nan Tang
- Analytical & Testing Center, Sichuan University, Chengdu, Sichuan 610064, PR China
| | - Jie Zhang
- Biliary Surgical Department of West China Hospital, Sichuan University, Chengdu, Sichuan 610064, PR China
| | - Tian-Yu Dong
- College of Chemistry, Sichuan University Chengdu, Sichuan 610064, PR China
| | - Rong-Xing Zhou
- Biliary Surgical Department of West China Hospital, Sichuan University, Chengdu, Sichuan 610064, PR China.
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34
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Healy GM, Salinas-Miranda E, Jain R, Dong X, Deniffel D, Borgida A, Hosni A, Ryan DT, Njeze N, McGuire A, Conlon KC, Dodd JD, Ryan ER, Grant RC, Gallinger S, Haider MA. Pre-operative radiomics model for prognostication in resectable pancreatic adenocarcinoma with external validation. Eur Radiol 2021; 32:2492-2505. [PMID: 34757450 DOI: 10.1007/s00330-021-08314-w] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 08/05/2021] [Accepted: 08/31/2021] [Indexed: 12/22/2022]
Abstract
OBJECTIVES In resectable pancreatic ductal adenocarcinoma (PDAC), few pre-operative prognostic biomarkers are available. Radiomics has demonstrated potential but lacks external validation. We aimed to develop and externally validate a pre-operative clinical-radiomic prognostic model. METHODS Retrospective international, multi-center study in resectable PDAC. The training cohort included 352 patients (pre-operative CTs from five Canadian hospitals). Cox models incorporated (a) pre-operative clinical variables (clinical), (b) clinical plus CT-radiomics, and (c) post-operative TNM model, which served as the reference. Outcomes were overall (OS)/disease-free survival (DFS). Models were assessed in the validation cohort from Ireland (n = 215, CTs from 34 hospitals), using C-statistic, calibration, and decision curve analyses. RESULTS The radiomic signature was predictive of OS/DFS in the validation cohort, with adjusted hazard ratios (HR) 2.87 (95% CI: 1.40-5.87, p < 0.001)/5.28 (95% CI 2.35-11.86, p < 0.001), respectively, along with age 1.02 (1.01-1.04, p = 0.01)/1.02 (1.00-1.04, p = 0.03). In the validation cohort, median OS was 22.9/37 months (p = 0.0092) and DFS 14.2/29.8 (p = 0.0023) for high-/low-risk groups and calibration was moderate (mean absolute errors 7%/13% for OS at 3/5 years). The clinical-radiomic model discrimination (C = 0.545, 95%: 0.543-0.546) was higher than the clinical model alone (C = 0.497, 95% CI 0.496-0.499, p < 0.001) or TNM (C = 0.525, 95% CI: 0.524-0.526, p < 0.001). Despite superior net benefit compared to the clinical model, the clinical-radiomic model was not clinically useful for most threshold probabilities. CONCLUSION A multi-institutional pre-operative clinical-radiomic model for resectable PDAC prognostication demonstrated superior net benefit compared to a clinical model but limited clinical utility at external validation. This reflects inherent limitations of radiomics for PDAC prognostication, when deployed in real-world settings. KEY POINTS • At external validation, a pre-operative clinical-radiomics prognostic model for pancreatic ductal adenocarcinoma (PDAC) outperformed pre-operative clinical variables alone or pathological TNM staging. • Discrimination and clinical utility of the clinical-radiomic model for treatment decisions remained low, likely due to heterogeneity of CT acquisition parameters. • Despite small improvements, prognosis in PDAC using state-of-the-art radiomics methodology remains challenging, mostly owing to its low discriminative ability. Future research should focus on standardization of CT protocols and acquisition parameters.
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Affiliation(s)
- Gerard M Healy
- Joint Department of Medical Imaging, University Health Network, Sinai Health System and Women's College Hospital, University of Toronto, Toronto, ON, Canada
- Department of Medical Imaging, University of Toronto, Toronto, ON, Canada
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada
| | | | - Rahi Jain
- Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Xin Dong
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada
| | - Dominik Deniffel
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada
- Department of Diagnostic and Interventional Radiology, Klinikum Rechts Der Isar, Technical University of Munich, Munich, Germany
| | - Ayelet Borgida
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Ali Hosni
- Radiation Medicine Program, Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
| | - David T Ryan
- Department of Radiology, St Vincent's University Hospital, Dublin, Ireland
| | - Nwabundo Njeze
- National Surgical Centre for Pancreatic Cancer, St. Vincent's University Hospital, Dublin, Ireland
| | - Anne McGuire
- National Surgical Centre for Pancreatic Cancer, St. Vincent's University Hospital, Dublin, Ireland
| | - Kevin C Conlon
- National Surgical Centre for Pancreatic Cancer, St. Vincent's University Hospital, Dublin, Ireland
- School of Medicine, Trinity College Dublin, Dublin, Ireland
| | - Jonathan D Dodd
- Department of Radiology, St Vincent's University Hospital, Dublin, Ireland
- School of Medicine, University College Dublin, Dublin, Ireland
| | - Edmund Ronan Ryan
- Department of Radiology, St Vincent's University Hospital, Dublin, Ireland
- National Surgical Centre for Pancreatic Cancer, St. Vincent's University Hospital, Dublin, Ireland
- School of Medicine, University College Dublin, Dublin, Ireland
| | - Robert C Grant
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
- PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, ON, Canada
| | - Steven Gallinger
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada
- PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, ON, Canada
- Surgical Oncology Program, Hepatobiliary Pancreatic, University Health Network, Toronto, ON, Canada
| | - Masoom A Haider
- Joint Department of Medical Imaging, University Health Network, Sinai Health System and Women's College Hospital, University of Toronto, Toronto, ON, Canada.
- Department of Medical Imaging, University of Toronto, Toronto, ON, Canada.
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
- PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, ON, Canada.
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Mortoglou M, Tabin ZK, Arisan ED, Kocher HM, Uysal-Onganer P. Non-coding RNAs in pancreatic ductal adenocarcinoma: New approaches for better diagnosis and therapy. Transl Oncol 2021; 14:101090. [PMID: 33831655 PMCID: PMC8042452 DOI: 10.1016/j.tranon.2021.101090] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Revised: 03/14/2021] [Accepted: 03/26/2021] [Indexed: 12/12/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies with a 5-year survival rate less than 8%, which has remained unchanged over the last 50 years. Early detection is particularly difficult due to the lack of disease-specific symptoms and a reliable biomarker. Multimodality treatment including chemotherapy, radiotherapy (used sparingly) and surgery has become the standard of care for patients with PDAC. Carbohydrate antigen 19-9 (CA 19-9) is the most common diagnostic biomarker; however, it is not specific enough especially for asymptomatic patients. Non-coding RNAs are often deregulated in human malignancies and shown to be involved in cancer-related mechanisms such as cell growth, differentiation, and cell death. Several micro, long non-coding and circular RNAs have been reported to date which are involved in PDAC. Aim of this review is to discuss the roles and functions of non-coding RNAs in diagnosis and treatments of PDAC.
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Affiliation(s)
- Maria Mortoglou
- Cancer Research Group, School of Life Sciences, University of Westminster, London W1W 6UW, UK.
| | - Zoey Kathleen Tabin
- Cancer Research Group, School of Life Sciences, University of Westminster, London W1W 6UW, UK.
| | - E Damla Arisan
- Institution of Biotechnology, Gebze Technical University, Gebze, Turkey.
| | - Hemant M Kocher
- Centre for Tumour Biology, Barts Cancer Institute-a CRUK Centre of Excellence, Queen Mary University London, London EC1M 6BQ, UK.
| | - Pinar Uysal-Onganer
- Cancer Research Group, School of Life Sciences, University of Westminster, London W1W 6UW, UK.
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Li S, Zhang G, Li X, Li X, Chen X, Xu Y, Ren H. Role of the preoperative circulating tumor DNA KRAS mutation in patients with resectable pancreatic cancer. Pharmacogenomics 2021; 22:657-667. [PMID: 34120460 DOI: 10.2217/pgs-2020-0183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: The prognosis of resectable pancreatic cancer patients with the same stage of disease is highly variable. The purpose of this study is to establish a scoring system for preoperative screening of resectable patients. Materials & methods: The clinical information and laboratory tests of 105 resectable patients with pancreatic cancer were enrolled and analyzed. Results: The consistency of clinical stage and pathological stage was poor (κ = 0.193; p < 0.003). We performed a comprehensive scoring system with KRAS mutations in circulating tumor DNA (mutKRAS ctDNA) for the resectable patients. Patients with higher scores were more prone to early postoperative recurrence and poorer prognosis. Conclusion: The scoring system can help preoperatively screen out resectable patients who are prone to early postoperative recurrence.
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Affiliation(s)
- Shengnan Li
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Gengpu Zhang
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Xin Li
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Xiaojie Li
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - XiaoBing Chen
- Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Yu Xu
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.,Department of Oncology, Tianjin Huanghe Hospital, Tianjin, 300060, China
| | - He Ren
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.,Department of Gastroenterology, Center of Tumor Immunology & Cytotherapy, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
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Li H, Zhou F, Cao Z, Tang Y, Huang Y, Li Y, Yi B, Yang J, Du P, Zhu D, Zhou J. Development and Validation of a Nomogram Based on Nutritional Indicators and Tumor Markers for Prognosis Prediction of Pancreatic Ductal Adenocarcinoma. Front Oncol 2021; 11:682969. [PMID: 34136406 PMCID: PMC8200845 DOI: 10.3389/fonc.2021.682969] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 05/11/2021] [Indexed: 12/11/2022] Open
Abstract
PURPOSE This study aimed to develop and validate a nomogram with preoperative nutritional indicators and tumor markers for predicting prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). METHODS We performed a bicentric, retrospective study including 155 eligible patients with PDAC. Patients were divided into a training group (n = 95), an internal validation group (n = 34), an external validation group (n = 26), and an entire validation group (n = 60). Cox regression analysis was conducted in the training group to identify independent prognostic factors to construct a nomogram for overall survival (OS) prediction. The performance of the nomogram was assessed in validation groups and through comparison with controlling nutritional status (CONUT) and prognostic nutrition index (PNI). RESULTS The least absolute shrinkage and selection operator (LASSO) regression, univariate and multivariate Cox regression analysis revealed that serum albumin and lymphocyte count were independent protective factors while CA19-9 and diabetes were independent risk factors. The concordance index (C-index) of the nomogram in the training, internal validation, external validation and entire validation groups were 0.777, 0.769, 0.759 and 0.774 respectively. The areas under curve (AUC) of the nomogram in each group were 0.861, 0.845, 0.773, and 0.814. C-index and AUC of the nomogram were better than those of CONUT and PNI in the training and validation groups. The net reclassification index (NRI), integrated discrimination improvement (IDI) and decision curve analysis showed improvement of accuracy of the nomogram in predicting OS and better net benefit in guiding clinical decisions in comparison with CONUT and PNI. CONCLUSIONS The nomogram incorporating four preoperative nutritional and tumor markers including serum albumin concentration, lymphocyte count, CA19-9 and diabetes mellitus could predict the prognosis more accurately than CONUT and PNI and may serve as a clinical decision support tool to determine what treatment options to choose.
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Affiliation(s)
- Haoran Li
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Fang Zhou
- Department of General Surgery, Changshu No. 2 People’s Hospital, Suzhou, China
| | - Zhifei Cao
- Department of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yuchen Tang
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yujie Huang
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Ye Li
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Bin Yi
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jian Yang
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Peng Du
- Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Dongming Zhu
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jian Zhou
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
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Abstract
OBJECTIVE In our study, we aim to evaluate in terms of patients the quality and reliability of the most relevant and most-watched videos uploaded on YouTube about pancreatic cancer. METHOD Before starting the study, YouTubeTM search terms were determined by consensus by two General Surgeons. Then, on 10/10/2020, the terms such as "pancreatic cancer", "diagnosis of pancreatic cancer" and "treatment of pancreatic cancer" were entered separately in the search bar of YouTube, "relevance" was selected among the filtering options and the most viewed videos were listed. The videos were evaluated with the Global Quality Scale (GQS), the DISCERN scoring system (Quality Criteria for Consumer Health Information, http://www.discern.org.uk), and video power index. RESULTS Among the 50 videos analysed, 19 videos were uploaded by hospital channels, 17 videos by health channels, seven videos by patients, four videos by blog channels, and three videos by doctors. The mean GQS score of the first researcher was 3.24 ± 0.99 and the mean GQS score of the second researcher was 3.18 ± 0.88 with a significantly high agreement between them (r= 0.628). The mean DISCERN score of the first researcher was 3.48 ± 0.77 and the mean DISCERN score of the second researcher was 3.46 ± 1.09 with a significantly high agreement between them (r= 0.814). CONCLUSION In our study, the majority of the videos were found to be of moderate quality. Healthcare professionals should be encouraged to upload more videos with useful content. However, we think that the uploaded videos should definitely go through a professional peer-review process before they are published.
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Affiliation(s)
- Guner Cakmak
- Department of General Surgery, Sakarya Training and Research Hospital, Sakarya, TUR
| | - Baris Mantoglu
- Department of General Surgery, Sakarya Training and Research Hospital, Sakarya, TUR
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Jugniot N, Bam R, Meuillet EJ, Unger EC, Paulmurugan R. Current status of targeted microbubbles in diagnostic molecular imaging of pancreatic cancer. Bioeng Transl Med 2021; 6:e10183. [PMID: 33532585 PMCID: PMC7823123 DOI: 10.1002/btm2.10183] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 08/19/2020] [Accepted: 08/19/2020] [Indexed: 12/14/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is often associated with a poor prognosis due to silent onset, resistance to therapies, and rapid spreading. Most patients are ineligible for curable surgery as they present with advanced disease at the time of diagnosis. Present diagnostic methods relying on anatomical changes have various limitations including difficulty to discriminate between benign and malignant conditions, invasiveness, the ambiguity of imaging results, or the inability to detect molecular biomarkers of PDAC initiation and progression. Therefore, new imaging technologies with high sensitivity and specificity are critically needed for accurately detecting PDAC and noninvasively characterizing molecular features driving its pathogenesis. Contrast enhanced targeted ultrasound (CETUS) is an upcoming molecular imaging modality that specifically addresses these issues. Unlike anatomical imaging modalities such as CT and MRI, molecular imaging using CETUS is promising for early and accurate detection of PDAC. The use of molecularly targeted microbubbles that bind to neovascular targets can enhance the ultrasound signal specifically from malignant PDAC tissues. This review discusses the current state of diagnostic imaging modalities for pancreatic cancer and places a special focus on ultrasound targeted-microbubble technology together with its clinical translatability for PDAC detection.
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Affiliation(s)
- Natacha Jugniot
- Department of RadiologyMolecular Imaging Program at Stanford, Stanford UniversityPalo AltoCaliforniaUSA
| | - Rakesh Bam
- Department of RadiologyMolecular Imaging Program at Stanford, Stanford UniversityPalo AltoCaliforniaUSA
| | | | | | - Ramasamy Paulmurugan
- Department of RadiologyMolecular Imaging Program at Stanford, Stanford UniversityPalo AltoCaliforniaUSA
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The Emerging Role of Microbiota and Microbiome in Pancreatic Ductal Adenocarcinoma. Biomedicines 2020; 8:biomedicines8120565. [PMID: 33287196 PMCID: PMC7761686 DOI: 10.3390/biomedicines8120565] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 11/27/2020] [Accepted: 12/02/2020] [Indexed: 12/12/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignant tumors due to the absence of biomarkers for early-stage detection and poor response to therapy. Since mounting evidence supports the role of microbiota composition in tumorigenesis and cancer treatment, the link between microbiome and PDAC has been described. In this review, we summarize the current knowledge regarding the impact of the gut and oral microbiome on the risk of PDAC development. Microenvironment-driven therapy and immune system interactions are also discussed. More importantly, we provide an overview of the clinical trials evaluating the microbiota role in the risk, prognosis, and treatment of patients suffering from PDAC and solid tumors. According to the research findings, immune tolerance might result from the microbiota-derived remodeling of pancreatic tumor microenvironment. Thus, microbiome profiling and targeting represent the potential trend to enhance antitumor immunity and improve the efficacy of PDAC treatment.
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Guerrero PE, Duran A, Ortiz MR, Castro E, Garcia-Velasco A, Llop E, Peracaula R. Microfibril associated protein 4 (MFAP4) is a carrier of the tumor associated carbohydrate sialyl-Lewis x (sLe x) in pancreatic adenocarcinoma. J Proteomics 2020; 231:104004. [PMID: 33038510 DOI: 10.1016/j.jprot.2020.104004] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 09/04/2020] [Accepted: 10/04/2020] [Indexed: 02/07/2023]
Abstract
Late diagnosis of pancreatic ductal adenocarcinoma (PDA) is one of the reasons of its low 5-year survival rate and it is due to its unspecific symptoms during the first stages of the disease and the lack of reliable serological markers. Since PDA shows an altered glycan expression, here we have focused on finding novel potential biomarkers, namely glycoproteins that express the tumor associated carbohydrate structure sialyl-Lewis x (sLex), which is described in PDA. Through a glycoproteomic approach, we have analyzed target proteins containing sLex from PDA tissues by 2DE and immunodetection techniques, and have identified by mass spectrometry the protein MFAP4 as a carrier of sLex in PDA. MFAP4 showed a higher expression in PDA tissues compared with pancreatic control tissues. In addition, the colocalization of sLex over MFAP4 was found only in PDA and not in control pancreatic tissues. The analysis of MFAP4 expression in PDA cell lines and their secretome, in combination with immunohistochemistry of pancreatic tissues, revealed that MFAP4 was not produced by PDA cells, but it was found in the pancreatic extracellular matrix. The specificity of MFAP4 glycoform containing sLex in PDA tissues shows its relevance as a potential PDA biomarker. SIGNIFICANCE: Despite advances in the field of cancer research, pancreatic ductal adenocarcinoma (PDA) lacks of a specific and sensitive biomarker for its early detection, when curative resection is still possible before metastases arise. Thus, efforts to discover new PDA biomarkers represent the first line in the fight against the increase of its incidence reported in recent years. Glycan alterations on glycoconjugates, such as glycoproteins have emerged as a rich source for the identification of novel cancer markers. In the present work, we aimed to shed light on novel biomarkers based on altered glycosylation in PDA, in particular those glycoproteins of PDA tissues carrying the tumor carbohydrate antigen sialyl-Lewis x (sLex). Through a glycoproteomic approach, we have shown that the glycoprotein MFAP4 carries sLex in PDA tissues and not in control pancreatic tissues. MFAP4 is found in the extracellular matrix in PDA and although its role in cancer progression is unclear, its sLex glycoform could be a potential biomarker in pancreatic ductal adenocarcinoma.
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Affiliation(s)
- Pedro Enrique Guerrero
- Biochemistry and Molecular Biology Unit, Department of Biology, University of Girona, 17003 Girona, Spain
| | - Adrià Duran
- Biochemistry and Molecular Biology Unit, Department of Biology, University of Girona, 17003 Girona, Spain
| | - Maria Rosa Ortiz
- Pathology Department, Josep Trueta University Hospital, 17007 Girona, Spain
| | - Ernesto Castro
- Hepato-biliary and Pancreatic Surgery Unit, Josep Trueta University Hospital, 17007 Girona, Spain
| | | | - Esther Llop
- Biochemistry and Molecular Biology Unit, Department of Biology, University of Girona, 17003 Girona, Spain..
| | - Rosa Peracaula
- Biochemistry and Molecular Biology Unit, Department of Biology, University of Girona, 17003 Girona, Spain..
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Kong L, Liu P, Fei X, Wu T, Wang Z, Zhang B, Li J, Tan X. A Prognostic Prediction Model Developed Based on Four CpG Sites and Weighted Correlation Network Analysis Identified DNAJB1 as a Novel Biomarker for Pancreatic Cancer. Front Oncol 2020; 10:1716. [PMID: 32984053 PMCID: PMC7477361 DOI: 10.3389/fonc.2020.01716] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 07/31/2020] [Indexed: 12/12/2022] Open
Abstract
Background The prognosis of pancreatic cancer, which is among the solid tumors associated with high mortality, is poor. There is a need to improve the overall survival rate of patients with pancreatic cancer. Materials and Methods The Cancer Genome Atlas (TCGA) dataset with 153 samples and the International Cancer Genome Consortium (ICGC) dataset with 235 samples were used as the discovery and validation cohorts, respectively. The least absolute shrinkage and selection operator regression was used to construct the prognostic prediction model based on the DNA methylation markers. The predictive efficiency of the model was evaluated based on the calibration curve, concordance index, receiver operating characteristic curve, area under the curve, and decision curve. The xenograft model and cellular functional experiments were used to investigate the potential role of DNAJB1 in pancreatic cancer. Results A prognostic prediction model based on four CpG sites (cg00609645, cg13512069, cg23811464, and cg03502002) was developed using TCGA dataset. The model effectively predicted the overall survival rate of patients with pancreatic cancer, which was verified in the ICGC dataset. Next, a nomogram model based on the independent prognostic factors was constructed to predict the overall survival rate of patients with pancreatic cancer. The nomogram model had a higher predictive value than TCGA or ICGC datasets. The low-risk group with improved prognosis exhibited less mutational frequency and high immune infiltration. The brown module with 247 genes derived from the WGCNA analysis was significantly correlated with the prognostic prediction model, tumor grade, clinical stage, and T stage. The bioinformatic analysis indicated that DNAJB1 can serve as a novel biomarker for pancreatic cancer. DNAJB1 knockdown significantly inhibited the proliferation, migration, and invasion of pancreatic cancer cells in vivo and in vitro. Conclusion The prognostic prediction model based on four CpG sites is a new method for predicting the prognosis of patients with pancreatic cancer. The molecular characteristic analyses, including Gene Ontology, Gene Set Enrichment Analysis, mutation spectrum, and immune infiltration of the subgroups, stratified by the model provided novel insights into the initiation and development of pancreatic cancer. DNAJB1 may serve as diagnostic and prognostic biomarkers for pancreatic cancer.
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Affiliation(s)
- Lingming Kong
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Peng Liu
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xiang Fei
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Tianyu Wu
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Zhongpeng Wang
- Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Baohui Zhang
- Department of Physiology, School of Life Sciences, China Medical University, Shenyang, China
| | - Jiatong Li
- Department of Orthopedics, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Xiaodong Tan
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
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Zhou S, Yan Y, Chen X, Zeng S, Wei J, Wang X, Gong Z, Xu Z. A two-gene-based prognostic signature for pancreatic cancer. Aging (Albany NY) 2020; 12:18322-18342. [PMID: 32966237 PMCID: PMC7585105 DOI: 10.18632/aging.103698] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Accepted: 06/29/2020] [Indexed: 02/06/2023]
Abstract
The purpose of this study was to identify a vital gene signature that has prognostic value for pancreatic cancer based on gene expression datasets from the Cancer Genome Atlas and Gene Expression Omnibus. A total of 34 genes were obtained by the univariate analysis, which were significantly associated with the overall survival of PC patients. After further analysis, Anillin (ANLN) and Histone H1c (HIST1H1C) were identified and considered to be the most significant prognostic genes among the 34 genes. A prognostic model based on these two genes was constructed, and successfully distinguished pancreatic cancer survival into high-risk and low-risk groups in the training set and testing set. Subsequently, independent predictive factors, including the age, margin condition and risk score, were then employed to construct the nomogram model. The area under curve for the nomogram model was 0.826 at 0.5 years and 0.726 at 1 year, and the C-index of the nomogram model was 0.664 higher than the others variables alone. These findings have indicated that high expression of ANLN and HIST1H1C predicted poor outcomes for patients with pancreatic cancer. The nomogram model based on the expression of two genes could be valuable for the guidance of clinical treatment.
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Affiliation(s)
- Shuyi Zhou
- The Hunan Institute of Pharmacy Practice and Clinical Research, Xiangya Hospital, Central South University, Changsha 410008, China
- Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital Xingsha Branch, People’s Hospital of Changsha County, Hunan Normal University, Changsha 410008, China
| | - Yuanliang Yan
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Xi Chen
- The Hunan Institute of Pharmacy Practice and Clinical Research, Xiangya Hospital, Central South University, Changsha 410008, China
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Shuangshuang Zeng
- The Hunan Institute of Pharmacy Practice and Clinical Research, Xiangya Hospital, Central South University, Changsha 410008, China
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Jie Wei
- The Hunan Institute of Pharmacy Practice and Clinical Research, Xiangya Hospital, Central South University, Changsha 410008, China
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Xiang Wang
- The Hunan Institute of Pharmacy Practice and Clinical Research, Xiangya Hospital, Central South University, Changsha 410008, China
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Zhicheng Gong
- The Hunan Institute of Pharmacy Practice and Clinical Research, Xiangya Hospital, Central South University, Changsha 410008, China
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Zhijie Xu
- Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, China
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Müller PC, Frey MC, Ruzza CM, Nickel F, Jost C, Gwerder C, Hackert T, Z'graggen K, Kessler U. Neoadjuvant Chemotherapy in Pancreatic Cancer: An Appraisal of the Current High-Level Evidence. Pharmacology 2020; 106:143-153. [PMID: 32966993 DOI: 10.1159/000510343] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 07/20/2020] [Indexed: 01/11/2023]
Abstract
At the time of diagnosis, only about 20% of patients with pancreatic ductal adenocarcinoma (PDAC) have resectable disease. PDAC treatment necessitates a multidisciplinary approach, and adjuvant chemotherapy after upfront resection is an established means of preventing recurrence. Neoadjuvant chemotherapy (NAT), originally introduced to downstage tumor size, is nowadays more frequently used for selection of patients with favorable tumor biology and to control potential micrometastases. While NAT is routinely applied in locally advanced (LA) PDAC, there is increasing evidence demonstrating benefits of NAT in borderline resectable (BR) PDAC. The concept of NAT has recently been tested in resectable PDAC, but to date NAT has been restricted to clinical trials, as the data are limited and no clear benefits have yet been shown in this patient group. This review summarizes the current evidence for NAT in resectable, BR, and LA PDAC, with a focus on high-level evidence and randomized controlled trials.
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Affiliation(s)
- Philip C Müller
- Department of Surgery, Hirslanden Klinik Beau-Site, Bern, Switzerland.,Swiss Pancreas Center, Hirslanden Klinik Beau-Site, Bern, Switzerland
| | - Michael C Frey
- Swiss Pancreas Center, Hirslanden Klinik Beau-Site, Bern, Switzerland.,Department of Pediatric Surgery, University Hospital Bern, University of Bern, Bern, Switzerland
| | - Claudio M Ruzza
- Department of Surgery, Hirslanden Klinik Beau-Site, Bern, Switzerland.,Swiss Pancreas Center, Hirslanden Klinik Beau-Site, Bern, Switzerland
| | - Felix Nickel
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Christian Jost
- Swiss Pancreas Center, Hirslanden Klinik Beau-Site, Bern, Switzerland.,Department of Gastroenterology, Hirslanden Klinik Beau-Site, Bern, Switzerland
| | - Christoph Gwerder
- Swiss Pancreas Center, Hirslanden Klinik Beau-Site, Bern, Switzerland.,Department of Oncology, Hirslanden Klinik Beau-Site, Bern, Switzerland
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Kaspar Z'graggen
- Department of Surgery, Hirslanden Klinik Beau-Site, Bern, Switzerland, .,Swiss Pancreas Center, Hirslanden Klinik Beau-Site, Bern, Switzerland,
| | - Ulf Kessler
- Department of Surgery, Hirslanden Klinik Beau-Site, Bern, Switzerland.,Swiss Pancreas Center, Hirslanden Klinik Beau-Site, Bern, Switzerland.,Department of Pediatric Surgery, University Hospital Bern, University of Bern, Bern, Switzerland
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Litman-Zawadzka A, Łukaszewicz-Zając M, Gryko M, Kulczyńska-Przybik A, Kędra B, Mroczko B. Specific Receptors for the Chemokines CXCR2 and CXCR4 in Pancreatic Cancer. Int J Mol Sci 2020; 21:ijms21176193. [PMID: 32867211 PMCID: PMC7504436 DOI: 10.3390/ijms21176193] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 08/25/2020] [Indexed: 12/16/2022] Open
Abstract
Background: The mortality rate of pancreatic cancer (PC) is equal to its incidence and the majority of PC patients die within a few months of diagnosis. Therefore, a search for new biomarkers useful in the diagnosis and prognosis of PC is ongoing. Objectives: The aim of our study was to compare the utility of CXCR2 and CXCR4 in the diagnosis and prediction of PC with classical tumor marker (carcinoembryonic antigen, CEA) and marker of inflammation–C-reactive protein (CRP). Patients and Methods: The study comprised 64 subjects — 32 PC patients and 32 healthy volunteers. Serum concentrations of tested proteins were analysed using immunological methods. Results: Serum CXCR2 and CXCR4 concentrations, similarly to those of CEA and CRP, were significantly elevated in PC patients compared to healthy controls. Moreover, concentrations of CXCR4 were significantly correlated with CXCR2 and CRP levels, while CRP concentrations were correlated with CXCR2 and CEA levels. The diagnostic sensitivity and the predictive value for negative (PV−ve) results for CXCR4 were similar to those of CEA and higher than those of CXCR2 and CRP, while the area under the ROC curve (AUC) for CXCR4 was the highest among all tested proteins (CXCR2, CEA, CRP). Moreover, serum CXCR2 was found to be a significant predictor of PC risk. Conclusions: CXCR4 is a better candidate for a tumor marker than CXCR2 in the diagnosis of PC, while serum CXCR2 is a significant predictor of PC risk.
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Affiliation(s)
- Ala Litman-Zawadzka
- Department of Neurodegeneration Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland; (A.K.-P.); (B.M.)
- Correspondence: ; Tel.: +48-85-8318785; Fax: +48-85-8318585
| | - Marta Łukaszewicz-Zając
- Department of Biochemical Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland;
| | - Mariusz Gryko
- Second Department of General Surgery, Medical University of Bialystok, 15-276 Bialystok, Poland; (M.G.); (B.K.)
| | - Agnieszka Kulczyńska-Przybik
- Department of Neurodegeneration Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland; (A.K.-P.); (B.M.)
| | - Bogusław Kędra
- Second Department of General Surgery, Medical University of Bialystok, 15-276 Bialystok, Poland; (M.G.); (B.K.)
| | - Barbara Mroczko
- Department of Neurodegeneration Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland; (A.K.-P.); (B.M.)
- Department of Biochemical Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland;
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Mattevi C, Garnier J, Marchese U, Ewald J, Gilabert M, Poizat F, Piana G, Delpero JR, Turrini O. Has the non-resection rate decreased during the last two decades among patients undergoing surgical exploration for pancreatic adenocarcinoma? BMC Surg 2020; 20:176. [PMID: 32758203 PMCID: PMC7430808 DOI: 10.1186/s12893-020-00835-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Accepted: 07/27/2020] [Indexed: 12/19/2022] Open
Abstract
Purpose To determine if improvement in imaging reduces the non-resection rate (NRR) among patients with pancreatic ductal adenocarcinoma (PDAC). Methods From 2000 to 2019, 751 consecutive patients with PDAC were considered eligible for a intention-to-treat pancreatectomy and entered the operating room. In April 2011, our institution acquired a dual energy spectral computed tomography (CT) scanner and liver diffusion weighted magnetic resonance imaging (DW-MRI) was included in the imaging workup. We consequently considered 2 periods of inclusion: period #1 (February 2000–March 2011) and period #2 (April 2011–August 2019). Results All patients underwent a preoperative CT scan with a median delay to surgery of 18 days. Liver DW-MRI was performed among 407 patients (54%). Median delay between CT and surgery decreased (21 days to 16 days, P < .01), and liver DW-MRI was significantly most prescribed during period #2 (14% vs 75%, P < .01). According to the intraoperative findings, the overall NRR was 24.5%, and remained stable over the two periods (25% vs 24%, respectively). While vascular invasion, liver metastasis, and carcinomatosis rates remained stable, para-aortic lymph nodes invasion rate (0.4% vs 4.6%; P < 0.001) significantly increased over the 2 periods. The mean size of the bigger extra pancreatic tumor significantly decrease (7.9 mm vs 6.4 mm (P < .01), respectively) when the resection was not done. In multivariate analysis, CA 19–9 < 500 U/mL (P < .01), and liver DW-MRI prescription (P < .01) favoured the resection. Conclusions Due to changes in our therapeutic strategies, the NRR did not decrease during two decades despite imaging improvement.
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Affiliation(s)
- C Mattevi
- Departement of Surgery, Institut Paoli-Calmettes, Marseille, France
| | - J Garnier
- Departement of Surgery, Institut Paoli-Calmettes, Marseille, France
| | - U Marchese
- Departement of Surgery, Institut Paoli-Calmettes, Marseille, France
| | - J Ewald
- Departement of Surgery, Institut Paoli-Calmettes, Marseille, France
| | - M Gilabert
- Departement of Oncology, Institut Paoli-Calmettes, Marseille, France
| | - F Poizat
- Departement of Pathology, Institut Paoli-Calmettes, Marseille, France
| | - G Piana
- Departement of Radiology, Institut Paoli-Calmettes, Marseille, France
| | - J R Delpero
- Departement of Surgery, Institut Paoli-Calmettes, Marseille, France
| | - O Turrini
- Departement of Surgery, Aix-Marseille University, Institut Paoli-Calmettes, CRCM, 232 boulevard Sainte Marguerite, 13009, Marseille, France.
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Study on the Diagnosis of Gastric Cancer by Magnetic Beads Extraction and Mass Spectrometry. BIOMED RESEARCH INTERNATIONAL 2020; 2020:2743060. [PMID: 32802837 PMCID: PMC7426759 DOI: 10.1155/2020/2743060] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 05/29/2020] [Accepted: 06/18/2020] [Indexed: 12/24/2022]
Abstract
Objective. This study constructed a model for the early diagnosis of gastric cancer by comparing the serum peptides profiles of patients with advanced gastric cancer and healthy people. And that model may be the potential to be applied for the efficacy evaluation and recurrence monitoring in gastric cancer. Methods. Serums of 30 healthy people and 30 advanced gastric cancer patients were matched by age and gender were collected. The serum peptide spectrum was obtained by MB-WCX concentration and MALDI-TOF MS analysis. Based on the analysis of the efficiency of differential peptides in the diagnosis of gastric cancer, we first established a model for the diagnosis of gastric cancer based on differential peptides and then carried out external verification. The diagnostic reliability of this model was further tested by compared with carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). Results. In this present study, we found the expression of two peptide peaks with a molecular weight of 2863 Da and 2953 Da were significantly increased in gastric cancer serum, while the expression of two peptide peaks with a molecular weight of 1945 Da and 2082 Da were significantly decreased. Depending on the characteristics of peptide expression, we constructed a diagnostic model, we compared the sensitivity and specificity of the model established by 2953 Da/1945 Da, and found this model is significantly higher than CEA and CA19-9. Conclusion. There were some differences in serum peptides profiles between patients with advanced gastric cancer and healthy people. The serum peptide diagnostic models based on 2953 Da and 1945 Da have high diagnostic efficiency for advanced gastric cancer. Our result indicated that this model was well worth further validation for clinical diagnosis.
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Manoochehri M, Wu Y, Giese NA, Strobel O, Kutschmann S, Haller F, Hoheisel JD, Moskalev EA, Hackert T, Bauer AS. SST gene hypermethylation acts as a pan-cancer marker for pancreatic ductal adenocarcinoma and multiple other tumors: toward its use for blood-based diagnosis. Mol Oncol 2020; 14:1252-1267. [PMID: 32243066 PMCID: PMC7266283 DOI: 10.1002/1878-0261.12684] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Revised: 03/07/2020] [Accepted: 03/13/2020] [Indexed: 02/06/2023] Open
Abstract
Aberrant DNA methylation is often involved in carcinogenesis. Our initial goal was to identify DNA methylation biomarkers associated with pancreatic cancer. A genomewide methylation study was performed on DNA from pancreatic ductal adenocarcinoma (PDAC) and endocrine pancreas tumors. Validation of DNA methylation patterns and concomitant alterations in expression of gene candidates was performed on patient samples and pancreatic cancer cell lines. Furthermore, validation was done on independent data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Finally, droplet digital PCR was employed to detect DNA methylation marks in cell-free (cf) DNA isolated from plasma samples of PDAC patients and cancer-free blood donors. Hypermethylation of the SST gene (encoding somatostatin) and concomitant downregulation of its expression were discovered in PDAC and endocrine tumor tissues while not being present in chronic pancreatitis (inflamed) tissues and normal pancreas. Fittingly, treatment with a somatostatin agonist (octreotide) reduced cell proliferation and migration of pancreatic cancer cells. Diagnostic performance of SST methylation in a receiver operating characteristic curve analysis was 100% and 89% for tissue and plasma samples, respectively. A large body of TCGA and GEO data confirmed SST hypermethylation and downregulation in PDAC and showed a similar effect in a broad spectrum of other tumor entities. SST promoter methylation represents a sensitive and promising molecular, pan-cancer biomarker detectable in tumor tissue, and liquid biopsy samples.
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Affiliation(s)
- Mehdi Manoochehri
- Division of Functional Genome AnalysisGerman Cancer Research Center (DKFZ)HeidelbergGermany
- Molecular Genetics of Breast CancerGerman Cancer Research Center (DKFZ)HeidelbergGermany
| | - Yenan Wu
- Division of Functional Genome AnalysisGerman Cancer Research Center (DKFZ)HeidelbergGermany
| | | | - Oliver Strobel
- Department of General SurgeryUniversity Hospital HeidelbergGermany
| | - Stefanie Kutschmann
- Division of Functional Genome AnalysisGerman Cancer Research Center (DKFZ)HeidelbergGermany
| | - Florian Haller
- Diagnostic Molecular PathologyInstitute of PathologyFriedrich‐Alexander UniversityErlangenGermany
| | - Jörg D. Hoheisel
- Division of Functional Genome AnalysisGerman Cancer Research Center (DKFZ)HeidelbergGermany
| | - Evgeny A. Moskalev
- Diagnostic Molecular PathologyInstitute of PathologyFriedrich‐Alexander UniversityErlangenGermany
| | - Thilo Hackert
- Department of General SurgeryUniversity Hospital HeidelbergGermany
| | - Andrea S. Bauer
- Division of Functional Genome AnalysisGerman Cancer Research Center (DKFZ)HeidelbergGermany
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Bararia A, Dey S, Gulati S, Ghatak S, Ghosh S, Banerjee S, Sikdar N. Differential methylation landscape of pancreatic ductal adenocarcinoma and its precancerous lesions. Hepatobiliary Pancreat Dis Int 2020; 19:205-217. [PMID: 32312637 DOI: 10.1016/j.hbpd.2020.03.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Accepted: 03/18/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND Pancreatic cancer is one of the most lethal diseases with an incidence almost equal to the mortality. In addition to having genetic causes, cancer can also be considered an epigenetic disease. DNA methylation is the premier epigenetic modification and patterns of aberrant DNA methylation are recognized to be a common hallmark of human tumor. In the multistage carcinogenesis of pancreas starting from precancerous lesions to pancreatic ductal adenocarcinoma (PDAC), the epigenetic changes play a significant role. DATA SOURCES Relevant studies for this review were derived via an extensive literature search in PubMed via using various keywords such as pancreatic ductal adenocarcinoma, precancerous lesions, methylation profile, epigenetic biomarkers that are relevant directly or closely associated with the concerned area of our interest. The literature search was intensively done considering a time frame of 20 years (1998-2018). RESULT In this review we have highlighted the hypermethylation and hypomethylation of the precancerous PDAC lesions (pancreatic intra-epithelial neoplasia, intraductal papillary mucinous neoplasm, mucinous cystic neoplasm and chronic pancreatitis) and PDAC along with the potential biomarkers. We have also achieved the early epigenetic driver that leads to progression from precancerous lesions to PDAC. A bunch of epigenetic driver genes leads to progression of precancerous lesions to PDAC (ppENK, APC, p14/5/16/17, hMLH1 and MGMT) are also documented. We summarized the importance of these observations in therapeutics and diagnosis of PDAC hence identifying the potential use of epigenetic biomarkers in epigenetic targeted therapy. Epigenetic inactivation occurs by hypermethylation of CpG islands in the promoter regions of tumor suppressor genes. We listed all hyper- and hypomethylation of CpG islands of several genes in PDAC including its precancerous lesions. CONCLUSIONS The concept of the review would help to understand their biological effects, and to determine whether they may be successfully combined with other epigenetic drugs. However, we need to continue our research to develop more specific DNA-demethylating agents, which are the targets for hypermethylated CpG methylation sites.
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Affiliation(s)
- Akash Bararia
- Human Genetics Unit, Indian Statistical Institute, Kolkata, India
| | - Subhankar Dey
- Department of Zoology, New Alipore College, University of Calcutta, Kolkata, India
| | - Sumit Gulati
- Department of Gastroenterological Surgery, Calcutta Medical Research Institute, Kolkata, India
| | - Supriyo Ghatak
- Department of Gastroenterological Surgery, Calcutta Medical Research Institute, Kolkata, India
| | - Shibajyoti Ghosh
- Department of General Surgery, Medical College and Hospital, Kolkata, India
| | - Sudeep Banerjee
- Department of Gastrointestinal Surgery, Tata Medical Center, Rajarhat, Kolkata, India
| | - Nilabja Sikdar
- Human Genetics Unit, Indian Statistical Institute, Kolkata, India.
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Yan Q, Hu D, Li M, Chen Y, Wu X, Ye Q, Wang Z, He L, Zhu J. The Serum MicroRNA Signatures for Pancreatic Cancer Detection and Operability Evaluation. Front Bioeng Biotechnol 2020; 8:379. [PMID: 32411694 PMCID: PMC7201024 DOI: 10.3389/fbioe.2020.00379] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 04/06/2020] [Indexed: 12/19/2022] Open
Abstract
Pancreatic cancer (PC) has high morbidity and mortality. It is the fourth leading cause of cancer death. Its diagnosis and treatment are difficult. Liquid biopsy makes early diagnosis of pancreatic cancer possible. We analyzed the expression profiles of 2,555 serum miRNAs in 100 pancreatic cancer patients and 150 healthy controls. With advanced feature selection methods, we identified 13 pancreatic cancer signature miRNAs that can classify the pancreatic cancer patients and healthy controls. For pancreatic cancer treatment, operation is still the first choice. But many pancreatic cancer patients are already inoperable. Therefore, we compared the 79 inoperable and 21 operable patients and identified 432 miRNAs that can predict whether a pancreatic cancer patient was operable. The functional analysis of the 13 pancreatic cancer signatures and the 432 operability miRNAs revealed the molecular mechanisms of pancreatic cancer and shield light on the diagnosis and therapy of pancreatic cancer in clinical practice.
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Affiliation(s)
- Qiuliang Yan
- Department of General Surgery, Jinhua People's Hospital, Jinhua, China
| | - Dandan Hu
- Department of General Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Maolan Li
- Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yan Chen
- Department of General Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiangsong Wu
- Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qinghuang Ye
- Department of General Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhijiang Wang
- Department of General Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lingzhe He
- Department of General Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jinhui Zhu
- Department of General Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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