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Pinson J, Henriques J, Beaussire L, Sarafan-Vasseur N, Sa Cunha A, Bachet JB, Vernerey D, Di Fiore F, Schwarz L. New Biomarkers to Define a Biological Borderline Situation for Pancreatic Adenocarcinoma: Results of an Ancillary Study of the PANACHE01-PRODIGE48 Trial. Ann Surg 2024; 280:734-744. [PMID: 39101207 DOI: 10.1097/sla.0000000000006468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/06/2024]
Abstract
OBJECTIVE To investigate in patients treated for a resectable pancreatic ductal adenocarcinoma [pancreatic adenocarcinoma (PA)], the prognostic value of baseline carbohydrate antigen 19.9 (CA19-9) and circulating tumor DNA (ctDNA) for overall survival (OS), to improve death risk stratification, based on a planned ancillary study from PANACHE01-PRODIGE 48 trial. BACKGROUND Biological borderline situation that was first used by the MD Anderson, became a standard practice following the international consensus conference in 2016 to manage PA. Regarding the risk of systemic disease, especially in the setting of "markedly elevated" CA19-9, neoadjuvant therapy is advised to avoid unnecessary surgery, with a risk of early recurrence. To best define biological borderline situations, new biomarkers are needed. METHODS Characteristics at diagnosis and OS were compared between patients with or without ctDNA status available. OS was estimated with the Kaplan-Meier method and compared with a log-rank test. The restricted cubic spline approach was used to identify the optimal threshold for biological parameters for death risk stratification. Univariate and multivariate Cox proportional hazard models were estimated to assess the association of ctDNA status and other parameters with OS. RESULTS Among the 132 patients from the primary population for analysis in the PANACHE01 -PRODIGE 48 trial, 92(71%) were available for ctDNA status at diagnosis. No selection bias was identified between patients with or without ctDNA status. Fourteen patients (15%) were ctDNA+ and exhibited a higher risk for death [ P = 0.0188; hazard ratio (95% CI): 2.28 (1.12-4.63)]. In the 92 patients with ctDNA status available among the other parameters analyzed, only CA19-9 was statically associated with OS in univariate analysis. Patients with a log of CA19-9 equal or superior to 4.4 that corresponds to a CA19-9 of 80 UI/mL were identified at higher risk for death [ P = 0.0143; hazard ratio (95% CI): 2.2 (1.15-4.19)]. In multivariate analysis, CA19-19 remained independently associated with OS ( P = 0.0323). When combining the 2 biomarkers, the median OS was 19.4 [IC 95%: 3.8-not reached (NR)] months, 30.2 (IC 95%: 17.1-NR) months and NR (IC 95%: 39.3-NR) for "CA19-9 high and ctDNA+ group," "CA19-9 high or ctDNA+ group," and "CA19-9 low and ctDNA- group," respectively (log-rank P = 0.0069). CONCLUSIONS Progress in the management of potentially operable PA remains limited, relying solely on strategies to optimize the sequence of complete treatment, based on modern multidrug chemotherapy (FOLFIRINOX, GemNabPaclitaxel) and surgical resection. The identification of risk criteria, such as the existence of systemic disease, is an important issue, currently referred to as "biological borderline disease." Few data, particularly from prospective studies, allow us to identify biomarkers other than CA19-9. Combining ctDNA with CA19-9 could be of interest to best define biological borderline situations in PA.
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Affiliation(s)
- Jean Pinson
- Department of Digestive Surgery, Rouen University Hospital, Rouen, France
- Department of Genomic and Personalized Medicine in Cancer and Neurological Disorders, Normandie University, UNIROUEN, Rouen University Hospital, Rouen, France
| | - Julie Henriques
- Methodology and Quality of Life in Oncology Unit, Besançon University Hospital, Besançon, France
| | - Ludivine Beaussire
- Department of Genomic and Personalized Medicine in Cancer and Neurological Disorders, Normandie University, UNIROUEN, Rouen University Hospital, Rouen, France
| | - Nasrin Sarafan-Vasseur
- Department of Genomic and Personalized Medicine in Cancer and Neurological Disorders, Normandie University, UNIROUEN, Rouen University Hospital, Rouen, France
| | - Antonio Sa Cunha
- Department of Hepato-Biliary and Pancreatic Surgery, and Liver Transplantation, Paul Brousse Hospital, AP-HP, Villejuif, France
| | - Jean-Baptiste Bachet
- Department of Hepato-Gastroenterology, Sorbonne University, Pitié-Salpêtrière Hospital, Paris, France
| | - Dewi Vernerey
- Methodology and Quality of Life in Oncology Unit, Besançon University Hospital, Besançon, France
| | - Frederic Di Fiore
- Department of Genomic and Personalized Medicine in Cancer and Neurological Disorders, Normandie University, UNIROUEN, Rouen University Hospital, Rouen, France
- Department of Digestive Oncology, Rouen University Hospital, Rouen, France
| | - Lilian Schwarz
- Department of Digestive Surgery, Rouen University Hospital, Rouen, France
- Department of Genomic and Personalized Medicine in Cancer and Neurological Disorders, Normandie University, UNIROUEN, Rouen University Hospital, Rouen, France
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Bhandare MS, Gupta V, Chaudhari V, Nandy K, Ostwal V, Ramaswamy A, Nashikkar C, Engineer R, Krishnatry R, Shrikhande SV. Differential impact of incrementally elevated CA 19-9 levels on prognosis of resected pancreatic ductal adenocarcinoma. HPB (Oxford) 2024; 26:1237-1247. [PMID: 38944571 DOI: 10.1016/j.hpb.2024.06.004] [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: 04/29/2024] [Revised: 06/11/2024] [Accepted: 06/12/2024] [Indexed: 07/01/2024]
Abstract
BACKGROUND CA 19-9 is an extremely useful biomarker for pancreatic ductal adenocarcinomas (PDACs). However, the optimal cut-off and prognostic significance at higher cut-offs are yet to be determined. METHODS Retrospective analysis included patients with PDAC who underwent curative resection from January 2010 to May 2020 at Tata Memorial Centre, Mumbai. The pretherapy CA 19-9 was dichotomized using various cut-off levels and analysed. RESULTS In 244 included patients, the median overall survival (OS) for those with CA19-9 level (IU/ml) < or >78, 200, 500, 1000, and 2000 was 27, 24, 23, 22, 21 months versus 18, 16, 15, 14, 13 months; respectively, and was statistically significant (p-value- 0.002, 0.001, 0.002, 0.002 and 0.004, respectively). The number of recurrences and mortality had significant correlation with CA 19-9 cut-offs. On multivariate analysis, adjuvant treatment completion (p-0.004) and decreasing or stable CA19-9 after Neoadjuvant therapy (NAT) (p- 0.031) were associated with improved OS. CONCLUSION The prognostic significance of CA 19-9 was observed at all the cut-off levels examined, beyond mere elevated value as per the standard cut-off level. In patients with high CA19-9 level, surgery should be offered if technically and conditionally feasible, only when a response in CA19-9 level to NAT is achieved.
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Affiliation(s)
- Manish S Bhandare
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai 400012, Maharashtra, India.
| | - Vikas Gupta
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai 400012, Maharashtra, India
| | - Vikram Chaudhari
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai 400012, Maharashtra, India
| | - Kunal Nandy
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai 400012, Maharashtra, India
| | - Vikas Ostwal
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Anant Ramaswamy
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | | | - Reena Engineer
- Department of Radiation Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Parel, Mumbai, Maharashtra, India
| | - Rahul Krishnatry
- Department of Radiation Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Parel, Mumbai, Maharashtra, India
| | - Shailesh V Shrikhande
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai 400012, Maharashtra, India
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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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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: 0] [Impact Index Per Article: 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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Gautam SK, Khan P, Natarajan G, Atri P, Aithal A, Ganti AK, Batra SK, Nasser MW, Jain M. Mucins as Potential Biomarkers for Early Detection of Cancer. Cancers (Basel) 2023; 15:1640. [PMID: 36980526 PMCID: PMC10046558 DOI: 10.3390/cancers15061640] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 02/25/2023] [Accepted: 02/27/2023] [Indexed: 03/10/2023] Open
Abstract
Early detection significantly correlates with improved survival in cancer patients. So far, a limited number of biomarkers have been validated to diagnose cancers at an early stage. Considering the leading cancer types that contribute to more than 50% of deaths in the USA, we discuss the ongoing endeavors toward early detection of lung, breast, ovarian, colon, prostate, liver, and pancreatic cancers to highlight the significance of mucin glycoproteins in cancer diagnosis. As mucin deregulation is one of the earliest events in most epithelial malignancies following oncogenic transformation, these high-molecular-weight glycoproteins are considered potential candidates for biomarker development. The diagnostic potential of mucins is mainly attributed to their deregulated expression, altered glycosylation, splicing, and ability to induce autoantibodies. Secretory and shed mucins are commonly detected in patients' sera, body fluids, and tumor biopsies. For instance, CA125, also called MUC16, is one of the biomarkers implemented for the diagnosis of ovarian cancer and is currently being investigated for other malignancies. Similarly, MUC5AC, a secretory mucin, is a potential biomarker for pancreatic cancer. Moreover, anti-mucin autoantibodies and mucin-packaged exosomes have opened new avenues of biomarker development for early cancer diagnosis. In this review, we discuss the diagnostic potential of mucins in epithelial cancers and provide evidence and a rationale for developing a mucin-based biomarker panel for early cancer detection.
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Affiliation(s)
- Shailendra K. Gautam
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Parvez Khan
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Gopalakrishnan Natarajan
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Pranita Atri
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Abhijit Aithal
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Apar K. Ganti
- Fred & Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA
- Division of Oncology-Hematology, Department of Internal Medicine, VA Nebraska Western Iowa Health Care System, University of Nebraska Medical Center, Omaha, NE 68105, USA
| | - Surinder K. Batra
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
- Fred & Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Mohd W. Nasser
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
- Fred & Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Maneesh Jain
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
- Fred & Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA
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Tong J, Jiang W, Mao S, Wu S, Lu C. Development and validation of a nomogram to predict liver metastasis for pancreatic ductal adenocarcinoma after radical resection. Front Oncol 2022; 12:1040411. [PMID: 36479089 PMCID: PMC9720266 DOI: 10.3389/fonc.2022.1040411] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Accepted: 10/24/2022] [Indexed: 09/07/2023] Open
Abstract
OBJECTIVES This study aimed to develop and externally validate a nomogram for predicting liver metastasis after radical resection in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS A total of 247 PDAC patients who underwent radical resection were retrospectively reviewed from January 2015 to March 2022 at Ningbo Medical Centre Lihuili Hospital Eastern Section, and used as a training cohort to develop the nomogram. 83 PDAC patients from the Ningbo Medical Centre Lihuili Hospital Xingning Section were enrolled as the validation cohort. The postoperative liver metastasis was recorded during the follow-up, and the liver metastasis-free survival was defined as the time from operation to the date of liver metastasis diagnosis or death. The nomogram was established based on independent prognostic factors selected by LASSO and multivariate Cox regression model. The performance was assessed using the concordance index (C-index) and calibration curves. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to determine the clinical utility of the nomogram model. RESULTS From the training cohort of 247 patients, a total of 132 patients developed liver metastasis during the follow-up, the 1-, 2- and 3- year liver metastasis-free survival were 52.4%, 43.5% and 40% respectively. The LASSO and multivariate Cox regression analysis indicated that postoperative CA125 (hazard ratio [HR] = 1.007, p <0.001), tumor differentiation (HR = 1.640, p = 0.010), tumor size (HR = 1.520, p = 0.029), lymph node ratio (HR = 1.897, p = 0.002) and portal/superior mesenteric/splenic vein invasion degree (PV/SMV/SV) (HR = 2.829, p <0.001) were the independent factors of liver metastasis. A nomogram with independent factors was developed and the C-index was 0.760 (95% confidence interval [CI], 0.720-0.799) and 0.739 (95% CI, 0.669-0.810) in the training and validation cohorts, respectively. The areas under curve (AUC) of the nomogram at 1-, 2- and 3-year were 0.815, 0.803 and 0.773 in the training cohort, and 0.765, 0.879 and 0.908 in the validation cohort, respectively, higher than those in TNM stage. Decision curve analysis (DCA) analysis revealed that the nomogram model provided superior net benefit in clinical utility. Liver metastasis-free survival curves showed a significant discriminatory ability for liver metastasis risk based on the nomogram (p <0.001). CONCLUSIONS The nomogram showed high accuracy in predicting liver metastasis for PDAC after radical resection, and may serve as a clinical support tool to guide personalized and prescient intervention.
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Affiliation(s)
| | | | - Shuqi Mao
- Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo University, Ningbo, China
| | - Shengdong Wu
- Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo University, Ningbo, China
| | - Caide Lu
- Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo University, Ningbo, China
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Shen F, Liu C, Zhang W, He S, Wang F, Wang J, Li Q, Zhou F. Serum levels of IL-6 and CRP can predict the efficacy of mFOLFIRINOX in patients with advanced pancreatic cancer. Front Oncol 2022; 12:964115. [PMID: 35965580 PMCID: PMC9372918 DOI: 10.3389/fonc.2022.964115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 07/05/2022] [Indexed: 12/24/2022] Open
Abstract
Objectives There is an urgent need for biomarkers that predict the survival outcome of patients diagnosed with metastatic pancreatic cancer, undergoing systemic chemotherapy. This study aimed to identify biomarkers associated with the survival of mPC patients treated with modified FOLFIRINOX (mFOLFIRINOX) as first-line chemotherapy. Methods This was a retrospective study of 30 patients with mPC who received mFOLFIRINOX between October 2018 and March 2021. Data on carcinoembryonic antigen (CEA), cancer antigen (CA)199, interleukin (IL)-6, C-reactive protein (CRP), neutrophils, platelets, lymphocytes, and albumin were collected and dichotomized using the upper or lower limit, as appropriate. These markers were examined for their association with progression-free survival (PFS). A receiver operating characteristic (ROC) curve analysis was used to explore a suitable model to predict mFOLFIRINOX effectiveness. Results IL-6 and CRP levels were associated with poor progression (P = 0.004 and P = <0.001, respectively) of mPC. The high IL-6 level was an independent poor prognostic factor for PFS (HR=4.66, 95%CI: 1.32-16.37, P=0.016) in the multivariable analysis. Patients with high IL-6 levels had a shorter PFS than those with low IL-6 levels (median PFS: 257 vs. 150 days, P=0.020). An increase in IL-6 and CRP levels during chemotherapy positively correlated with disease progression (P = <0.001 for both). The model combining IL-6 with CRP levels helped predict the outcomes of mPC patients treated with mFOLFIRINOX (AUC: 0.811, 95%CI: 0.639-0.983, P=0.003). Conclusions The serum levels of IL-6 and CRP might be considered as valuable biomarkers in predicting the outcomes of patients with mPC who received the mFOLFIRINOX regimen.
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Affiliation(s)
- Feifei Shen
- Department of Oncology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Chuan Liu
- Department of Oncology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Weiguo Zhang
- Department of Radiology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Sijia He
- Department of Oncology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Fan Wang
- Department of Oncology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jingjue Wang
- Department of Oncology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Qi Li
- Department of Oncology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Fei Zhou
- Department of Oncology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- *Correspondence: Fei Zhou,
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Perales S, Torres C, Jimenez-Luna C, Prados J, Martinez-Galan J, Sanchez-Manas JM, Caba O. Liquid biopsy approach to pancreatic cancer. World J Gastrointest Oncol 2021; 13:1263-1287. [PMID: 34721766 PMCID: PMC8529923 DOI: 10.4251/wjgo.v13.i10.1263] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 05/18/2021] [Accepted: 08/27/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer (PC) continues to pose a major clinical challenge. There has been little improvement in patient survival over the past few decades, and it is projected to become the second leading cause of cancer mortality by 2030. The dismal 5-year survival rate of less than 10% after the diagnosis is attributable to the lack of early symptoms, the absence of specific biomarkers for an early diagnosis, and the inadequacy of available chemotherapies. Most patients are diagnosed when the disease has already metastasized and cannot be treated. Cancer interception is vital, actively intervening in the malignization process before the development of a full-blown advanced tumor. An early diagnosis of PC has a dramatic impact on the survival of patients, and improved techniques are urgently needed to detect and evaluate this disease at an early stage. It is difficult to obtain tissue biopsies from the pancreas due to its anatomical position; however, liquid biopsies are readily available and can provide useful information for the diagnosis, prognosis, stratification, and follow-up of patients with PC and for the design of individually tailored treatments. The aim of this review was to provide an update of the latest advances in knowledge on the application of carbohydrates, proteins, cell-free nucleic acids, circulating tumor cells, metabolome compounds, exosomes, and platelets in blood as potential biomarkers for PC, focusing on their clinical relevance and potential for improving patient outcomes.
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Affiliation(s)
- Sonia Perales
- Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Granada 18071, Spain
| | - Carolina Torres
- Department of Biochemistry and Molecular Biology III and Immunology, Faculty of Sciences, University of Granada, Granada 18071, Spain
| | - Cristina Jimenez-Luna
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada 18100, Spain
| | - Jose Prados
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada 18100, Spain
| | - Joaquina Martinez-Galan
- Department of Medical Oncology, Hospital Universitario Virgen de las Nieves, Granada 18011, Spain
| | | | - Octavio Caba
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada 18100, Spain
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Wei M, Gu B, Song S, Zhang B, Wang W, Xu J, Yu X, Shi S. A Novel Validated Recurrence Stratification System Based on 18F-FDG PET/CT Radiomics to Guide Surveillance After Resection of Pancreatic Cancer. Front Oncol 2021; 11:650266. [PMID: 34055620 PMCID: PMC8149949 DOI: 10.3389/fonc.2021.650266] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 04/19/2021] [Indexed: 12/20/2022] Open
Abstract
objective Despite the heterogeneous biology of pancreatic cancer, similar surveillance schemas have been used. Identifying the high recurrence risk population and conducting prompt intervention may improve prognosis and prolong overall survival. Methods One hundred fifty-six resectable pancreatic cancer patients who had undergone 18F-FDG PET/CT from January 2013 to December 2018 were retrospectively reviewed. The patients were categorized into a training cohort (n = 109) and a validation cohort (n = 47). LIFEx software was used to extract radiomic features from PET/CT. The risk stratification system was based on predictive factors for recurrence, and the index of prediction accuracy was used to reflect both the discrimination and calibration. Results Overall, seven risk factors comprising the rad-score and clinical variables that were significantly correlated with relapse were incorporated into the final risk stratification system. The 1-year recurrence-free survival differed significantly among the low-, intermediate-, and high-risk groups (85.5, 24.0, and 9.1%, respectively; p < 0.0001). The C-index of the risk stratification system in the development cohort was 0.890 (95% CI, 0.835-0.945). Conclusion The 18F-FDG PET/CT-based radiomic features and clinicopathological factors demonstrated good performance in predicting recurrence after pancreatectomy in pancreatic cancer patients, providing a strong recommendation for an adequate adjuvant therapy course in all patients. The high-risk recurrence population should proceed with closer follow-up in a clinical setting.
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Affiliation(s)
- Miaoyan Wei
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Pancreatic Cancer Multidisciplinary Center, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Bingxin Gu
- Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China.,Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.,Center for Biomedical Imaging, Fudan University, Shanghai, China
| | - Shaoli Song
- Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China.,Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.,Center for Biomedical Imaging, Fudan University, Shanghai, China
| | - Bo Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Pancreatic Cancer Multidisciplinary Center, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Wei Wang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Pancreatic Cancer Multidisciplinary Center, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Jin Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Pancreatic Cancer Multidisciplinary Center, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Pancreatic Cancer Multidisciplinary Center, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Si Shi
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Pancreatic Cancer Multidisciplinary Center, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China
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10
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Feng Z, Li K, Lou J, Wu Y, Peng C. An EMT-Related Gene Signature for Predicting Response to Adjuvant Chemotherapy in Pancreatic Ductal Adenocarcinoma. Front Cell Dev Biol 2021; 9:665161. [PMID: 33996821 PMCID: PMC8119901 DOI: 10.3389/fcell.2021.665161] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Accepted: 04/13/2021] [Indexed: 12/11/2022] Open
Abstract
Background For pancreatic ductal adenocarcinoma (PDAC) patients, chemotherapy failure is the major reason for postoperative recurrence and poor outcomes. Establishment of novel biomarkers and models for predicting chemotherapeutic efficacy may provide survival benefits by tailoring treatments. Methods Univariate cox regression analysis was employed to identify EMT-related genes with prognostic potential for DFS. These genes were subsequently submitted to LASSO regression analysis and multivariate cox regression analysis to identify an optimal gene signature in TCGA training cohort. The predictive accuracy was assessed by Kaplan–Meier (K-M), receiver operating characteristic (ROC) and calibration curves and was validated in PACA-CA cohort and our local cohort. Pathway enrichment and function annotation analyses were conducted to illuminate the biological implication of this risk signature. Results LASSO and multivariate Cox regression analyses selected an 8-gene signature comprised DLX2, FGF9, IL6R, ITGB6, MYC, LGR5, S100A2, and TNFSF12. The signature had the capability to classify PDAC patients with different DFS, both in the training and validation cohorts. It provided improved DFS prediction compared with clinical indicators. This signature was associated with several cancer-related pathways. In addition, the signature could also predict the response to immune-checkpoint inhibitors (ICIs)-based immunotherapy. Conclusion We established a novel EMT-related gene signature that was capable of predicting therapeutic response to adjuvant chemotherapy and immunotherapy. This signature might facilitate individualized treatment and appropriate management of PDAC patients.
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Affiliation(s)
- Zengyu Feng
- 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.,Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Kexian 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
| | - Jianyao Lou
- Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yulian Wu
- Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Chenghong Peng
- 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
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11
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Cheng H, Luo G, Jin K, Xiao Z, Qian Y, Gong Y, Yu X, Liu C. Predictive Values of Preoperative Markers for Resectable Pancreatic Body and Tail Cancer Determined by MDCT to Detect Occult Metastases. World J Surg 2021; 45:2185-2190. [PMID: 33774691 DOI: 10.1007/s00268-021-06047-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/15/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND To evaluate the clinical value of preoperative markers in predicting occult metastases in resectable pancreatic body and tail cancer judged by a recent multidetector computed tomography (MDCT) scan of the abdomen. METHODS The data from a retrospective collected database from 2010 to 2019 with 699 patients who had MDCT scan predicted resectable mass in pancreatic body and tail and were pathological confirmed as adenocarcinoma after surgery. Receiver operating characteristic (ROC) curve was plotted for serum CA19-9, CA125, CEA and tumor size measured by MDCT. The optimal cut-off point-related sensitivity and specificity were calculated, respectively. RESULTS Occult metastases were found in 73 (73/699, 10.4%) pancreatic body and tail cancer patients underwent exploration. The area under curve (AUC) for CA19-9, CA125, CEA and tumor size were 0.624, 0.733, 0.561 and 0.697, respectively. The optimal cut-off for CA19-9, CA125 and tumor size is 226 U/ml, 22.1 U/ml and 3.3 cm, respectively. The sensitivity and specificity of CA19-9 for predicting occult metastases were 67.1% and 60.4%, 72.6% and 64.7% for CA125, 80.8% and 51.4% for tumor size. CONCLUSION CA125 is superior to CA19-9 and tumor size for predicting occulting metastases in MDCT scan suggested resectable pancreatic body and tail cancer. The high level of CA125 (≥ 22.1 U/ml) is regarded as high risk for occulting metastases, and laparoscopy should be applied for these patients.
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Affiliation(s)
- He Cheng
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 DongAn Road, 200032, Xuhui, Shanghai, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Guopei Luo
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 DongAn Road, 200032, Xuhui, Shanghai, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Kaizhou Jin
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 DongAn Road, 200032, Xuhui, Shanghai, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Zhiwen Xiao
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 DongAn Road, 200032, Xuhui, Shanghai, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Yunzhen Qian
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 DongAn Road, 200032, Xuhui, Shanghai, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Yitao Gong
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 DongAn Road, 200032, Xuhui, Shanghai, People's Republic of China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 DongAn Road, 200032, Xuhui, Shanghai, People's Republic of China. .,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. .,Shanghai Pancreatic Cancer Institute, Shanghai, China.
| | - Chen Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 DongAn Road, 200032, Xuhui, Shanghai, People's Republic of China. .,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. .,Shanghai Pancreatic Cancer Institute, Shanghai, China.
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12
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Skulimowski A, Durczyński A, Strzelczyk J, Hogendorf P. Comparison of clinical usefulness of serum Ca125 and CA19-9 in pancreatic adenocarcinoma diagnosis: meta-analysis and systematic review of literature. Biomarkers 2021; 26:287-295. [PMID: 33459070 DOI: 10.1080/1354750x.2021.1876770] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
INTRODUCTION Pancreatic adenocarcinoma remains one of the most lethal cancers. The only recommended biomarker CA19-9 proves to be not accurate enough to establish a certain diagnosis. Therefore, a determination of usefulness of other biomarkers is essential. Our aim was to compare the specificity and sensitivity of Ca125 and CA19-9 by means of meta-analysis. The systematic review of combined tests (CA19-9 + Ca125) was also performed. METHODS We conducted a systematic search of Medline (via PubMed) and Ovid. After screening of abstracts and the assessment of full-texts, nine studies (number of patients, n = 1599) were included. Hierarchical summary receiver under operator curve (hsROC) model was applied to estimate the diagnostic accuracy. RESULTS CA19-9 sensitivity and specificity were 0.748 (95%CI 0.676-0.809) and 0.782 (95%CI 0.716-0.836), respectively. These values were estimated on 0.593 (95%CI 0.489-0.69) and 0.754 (95%CI 0.817-0.668) for Ca125. Regarding the heterogeneity of studies, a strong threshold effect for Ca125 and moderate one for CA19-9 were found. CONCLUSIONS Our meta-analysis did not prove the superiority of Ca125. It should be nevertheless noted that the sparsity of studies precludes accurate analysis of various factors' influence. The review of proposed combined tests shows that CA19-9 + Ca125 models are generally characterized by higher sensitivity.
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Affiliation(s)
- Aleksander Skulimowski
- Department of General and Transplant Surgery, N. Barlicki Memorial Clinical Hospital, Medical University of Lodz, Lodz, Poland
| | - Adam Durczyński
- Department of General and Transplant Surgery, N. Barlicki Memorial Clinical Hospital, Medical University of Lodz, Lodz, Poland
| | - Janusz Strzelczyk
- Department of General and Transplant Surgery, N. Barlicki Memorial Clinical Hospital, Medical University of Lodz, Lodz, Poland
| | - Piotr Hogendorf
- Department of General and Transplant Surgery, N. Barlicki Memorial Clinical Hospital, Medical University of Lodz, Lodz, Poland
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13
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Mu Y, Wang D, Bie L, Luo S, Mu X, Zhao Y. Glypican-1-targeted and gemcitabine-loaded liposomes enhance tumor-suppressing effect on pancreatic cancer. Aging (Albany NY) 2020; 12:19585-19596. [PMID: 33035197 PMCID: PMC7732280 DOI: 10.18632/aging.103918] [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: 02/12/2020] [Accepted: 07/25/2020] [Indexed: 01/24/2023]
Abstract
Liposomes (LPs) as promising drug delivery systems are widely applied in cancer therapy. This study aimed to investigate the effect of glypican-1 (GPC1)-targeted and gemcitabine (GEM)-loaded LP [GPC1-LP (GEM)] on cell proliferation and apoptosis in PANC-1s, as well as on orthotopic pancreatic cancer (PDAC) mice. The GPC1-LP (GEM) and LP (GEM) was prepared, and then the size distribution of GPC1-LP (GEM) was analyzed by dynamic light scattering (DLS). In vitro drug release assay of GPC1-LP (GEM) and LP (GEM) was performed, and the expression of GPC1 in PANC1 cells was detected as well. Next, the effects of free GEM, LP (GEM) and GPC1-LP (GEM) on cell viability, clone number, and apoptosis, as well as the expression of proteins associated with apoptosis were measured in 239T and PANC-1 cells. Furthermore, the body weight and tumor size of orthotopic PDAC mice were evaluated following the treatment of free GEM, LP (GEM) or GPC1-LP (GEM). LP (GEM) and GPC1-LP (GEM) were successfully prepared with a successful GEM release within 24 h. In addition, GPC1 was positively expressed in PANC-1 cells but not 293T cells. These findings provided more insights into the anti-tumor potential for the biomedical application of GPC1-LP (GEM) in PDAC.
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Affiliation(s)
- Yu Mu
- Department of Oncology, Affiliated Cancer Hospital of Zhengzhou University / Henan Cancer Hospital, Zhengzhou, China
| | - Dezhi Wang
- East China Normal University, Shanghai, China
| | - Liangyu Bie
- Department of Oncology, Affiliated Cancer Hospital of Zhengzhou University / Henan Cancer Hospital, Zhengzhou, China
| | - Suxia Luo
- Department of Oncology, Affiliated Cancer Hospital of Zhengzhou University / Henan Cancer Hospital, Zhengzhou, China
| | - Xiaoqian Mu
- Department of Oncology, Affiliated Cancer Hospital of Zhengzhou University / Henan Cancer Hospital, Zhengzhou, China
| | - Yanqiu Zhao
- Department of Oncology, Affiliated Cancer Hospital of Zhengzhou University / Henan Cancer Hospital, Zhengzhou, China
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14
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Tumour markers and their utility in imaging of abdominal and pelvic malignancies. Clin Radiol 2020; 76:99-107. [PMID: 32861463 DOI: 10.1016/j.crad.2020.07.033] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 07/31/2020] [Indexed: 01/15/2023]
Abstract
The utility of tumour biomarkers has increased considerably in the era of personalised medicine and individualised therapy in oncology. Biomarkers may be prognostic or predictive, and only a handful of markers are currently US Food and Drug Administration (FDA)-approved for clinical use. Tumour markers have a wide array of uses such as screening, establishing a differential diagnosis, assessing risk, prognosis, and treatment response, as well as monitoring disease status. Major overlap exists between biomarkers and their associated pathologies; therefore, despite suggestive imaging features, establishing a differential diagnosis may be challenging for the radiologist. We review common biomarkers that are of interest to radiologists such as carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH), prostate-specific antigen (PSA), beta human chorionic gonadotropin (β-hCG), carbohydrate antigen 19-9 (CA 19-9), alpha fetoprotein (AFP), and carbohydrate or cancer antigen 125 (CA 125), as well as their associated malignant and non-malignant pathologies. We also present relevant case examples from our practice.
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15
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Wang S, You L, Dai M, Zhao Y. Mucins in pancreatic cancer: A well-established but promising family for diagnosis, prognosis and therapy. J Cell Mol Med 2020; 24:10279-10289. [PMID: 32745356 PMCID: PMC7521221 DOI: 10.1111/jcmm.15684] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 06/12/2020] [Accepted: 07/09/2020] [Indexed: 12/13/2022] Open
Abstract
Mucins are a family of multifunctional glycoproteins that mostly line the surface of epithelial cells in the gastrointestinal tract and exert pivotal roles in gut lubrication and protection. Pancreatic cancer is a lethal disease with poor early diagnosis, limited therapeutic effects, and high numbers of cancer‐related deaths. In this review, we introduce the expression profiles of mucins in the normal pancreas, pancreatic precursor neoplasia and pancreatic cancer. Mucins in the pancreas contribute to biological processes such as the protection, lubrication and moisturization of epithelial tissues. They also participate in the carcinogenesis of pancreatic cancer and are used as diagnostic biomarkers and therapeutic targets. Herein, we discuss the important roles of mucins that lead to the lethality of pancreatic adenocarcinoma, particularly MUC1, MUC4, MUC5AC and MUC16 in disease progression, and present a comprehensive analysis of the clinical application of mucins and their promising roles in cancer treatment to gain a better understanding of the role of mucins in pancreatic cancer.
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Affiliation(s)
- Shunda Wang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Lei You
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Menghua Dai
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Yupei Zhao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
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16
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Kim H, Kang KN, Shin YS, Byun Y, Han Y, Kwon W, Kim CW, Jang JY. Biomarker Panel for the Diagnosis of Pancreatic Ductal Adenocarcinoma. Cancers (Basel) 2020; 12:cancers12061443. [PMID: 32492943 PMCID: PMC7352313 DOI: 10.3390/cancers12061443] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 05/29/2020] [Accepted: 05/30/2020] [Indexed: 12/27/2022] Open
Abstract
A single tumor marker has a low diagnostic value in pancreatic cancer. Combinations of multiple biomarkers and unique analysis algorithms can be applied to overcome these limitations. This study sought to develop diagnostic algorithms using multiple biomarker panels and to validate their performance in the diagnosis of pancreatic ductal adenocarcinoma (PDAC). We used blood samples from 180 PDAC patients and 573 healthy controls. Candidate markers consisted of 11 markers that are commonly expressed in various cancers and which have previously demonstrated increased expression in pancreatic cancer. Samples were divided into training and validation sets. Five linear or non-linear classification methods were used to determine the optimal model. Differences were identified in 10 out of the 11 markers tested. We identified 2047 combinations, all of which were applied to 5 separate algorithms. The new biomarker combination consisted of 6 markers (ApoA1, CA125, CA19-9, CEA, ApoA2, and TTR). The area under the curve, specificity, and sensitivity were 0.992, 95%, and 96%, respectively, in the training set. Meanwhile, the measures were 0.993, 96%, and 93% in the validation set. This study demonstrated the utility of multiple biomarker combinations in the early detection of PDAC. A diagnostic panel of 6 biomarkers was developed and validated. These algorithms will assist in the early diagnosis of PDAC.
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Affiliation(s)
- Hongbeom Kim
- Departments of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; (H.K.); (Y.B.); (Y.H.); (W.K.)
| | - Kyung Nam Kang
- BIOINFRA Life Science Inc., Seoul 03127, Korea; (K.N.K.); (Y.S.S.); (C.W.K.)
| | - Yong Sung Shin
- BIOINFRA Life Science Inc., Seoul 03127, Korea; (K.N.K.); (Y.S.S.); (C.W.K.)
| | - Yoonhyeong Byun
- Departments of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; (H.K.); (Y.B.); (Y.H.); (W.K.)
| | - Youngmin Han
- Departments of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; (H.K.); (Y.B.); (Y.H.); (W.K.)
| | - Wooil Kwon
- Departments of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; (H.K.); (Y.B.); (Y.H.); (W.K.)
| | - Chul Woo Kim
- BIOINFRA Life Science Inc., Seoul 03127, Korea; (K.N.K.); (Y.S.S.); (C.W.K.)
| | - Jin-Young Jang
- Departments of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea; (H.K.); (Y.B.); (Y.H.); (W.K.)
- Correspondence: ; Tel.: +82-2-2072-2194; Fax: +82-2-766-3975
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17
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Fenocchio E, Filippi R, Lombardi P, Quarà V, Milanesio M, Aimar G, Leone F, Aglietta M. Is There a Standard Adjuvant Therapy for Resected Pancreatic Cancer? Cancers (Basel) 2019; 11:E1547. [PMID: 31614884 PMCID: PMC6826876 DOI: 10.3390/cancers11101547] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 10/07/2019] [Accepted: 10/11/2019] [Indexed: 12/19/2022] Open
Abstract
Surgical resection remains the only treatment that offers a potential chance of long-term survival. Unfortunately, about 80% of patients treated with curative intent will develop recurrence. Since 2001, adjuvant therapy with gemcitabine or 5-fluorouracyle was recommended. This approach allows a median overall survival (OS) of around 23 months, and 5-year survival of 22%. In recent years, two phase-3 trials investigating new chemotherapy regimens resulted in considerably improved survival times. The doublet gemcitabine-capecitabine has shown improvement in OS from 25.5 to 28 months (p = 0.032) compared to gemcitabine, in the ESPAC-4 trial. Later, preliminary results of PRODIGE 24 trial presented at the 2018 ASCO meeting showed a superiority of a combination chemotherapy regimen with fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) when compared to gemcitabine alone, both in terms of median disease-free survival (21.6 vs. 12.8 months, p < 0.0001) and OS (54.4 vs. 35 months, p = 0.003). Contrary to chemotherapy, the role of adjuvant radiotherapy is still controversial, even in the case of R1 surgery. A randomized trial exploring the role of chemoradiotherapy in this setting is now ongoing in the US (RTOG-0848). Overall, the management of localized pancreatic adenocarcinoma is evolving. In this review, we summarize the current status and the most up-to-date developments in adjuvant treatment.
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Affiliation(s)
- Elisabetta Fenocchio
- Multidisciplinary Outpatient Oncology Clinic, Candiolo Cancer Institute, FPO-IRCCS, Strada Provinciale 142, km 3.95, 10060 Candiolo (TO), Italy.
| | - Roberto Filippi
- Department of Oncology, University of Turin Medical School, Strada Provinciale 142, km 3.95, 10060 Candiolo (TO), Italy.
| | - Pasquale Lombardi
- Department of Oncology, University of Turin Medical School, Strada Provinciale 142, km 3.95, 10060 Candiolo (TO), Italy.
| | - Virginia Quarà
- Department of Oncology, University of Turin Medical School, Strada Provinciale 142, km 3.95, 10060 Candiolo (TO), Italy.
| | - Michela Milanesio
- Department of Oncology, University of Turin Medical School, Strada Provinciale 142, km 3.95, 10060 Candiolo (TO), Italy.
| | - Giacomo Aimar
- Department of Oncology, University of Turin Medical School, Strada Provinciale 142, km 3.95, 10060 Candiolo (TO), Italy.
| | - Francesco Leone
- Division of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, Strada Provinciale 142, km 3.95, 10060 Candiolo (TO), Italy.
- Department of Oncology, Azienda Sanitaria Locale di Biella, 13875 Ponderano (BI), Italy.
| | - Massimo Aglietta
- Department of Oncology, University of Turin Medical School, Strada Provinciale 142, km 3.95, 10060 Candiolo (TO), Italy.
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18
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Qiu W, Zhang H, Chen X, Song L, Cui W, Ren S, Wang Y, Guo K, Li D, Chen R, Wang Z. A GPC1-targeted and gemcitabine-loaded biocompatible nanoplatform for pancreatic cancer multimodal imaging and therapy. Nanomedicine (Lond) 2019; 14:2339-2353. [PMID: 31414945 DOI: 10.2217/nnm-2019-0063] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Aim: Biomarker-targeted nanocarrier holds promise for early diagnosis and effective therapy of cancer. Materials & methods: This work successfully designs and evaluates GPC1-targeted, gemcitabine (GEM)-loaded multifunctional gold nanocarrier for near-infrared fluorescence (NIRF)/MRI and targeted chemotherapy against pancreatic cancer in vitro and in vivo. Results: Blood biochemical and histological analyses show that the in vivo toxicity of GPC1-GEM-nanoparticles (NPs) was negligible. Both in vitro and in vivo studies demonstrate that GPC1-GEM-NPs can be used as NIRF/MR contrast agent for pancreatic cancer detection. Treatment of xenografted mice with GPC1-GEM-NPs shows a higher tumor inhibitory effect compared with controls. Conclusion: This novel theranostic nanoplatform provides early diagnostic and effective therapeutic potential for pancreatic cancer.
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Affiliation(s)
- Wenli Qiu
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, PR China
| | - Huifeng Zhang
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, PR China
| | - Xiao Chen
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, PR China
| | - Lina Song
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, PR China
| | - Wenjing Cui
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, PR China
| | - Shuai Ren
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, PR China
| | - Yajie Wang
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, PR China
| | - Kai Guo
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, PR China
| | - Donghui Li
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Rong Chen
- Department of Diagnostic Radiology & Nuclear Medicine, University of Maryland School of Medicine, MD 21201, USA
| | - Zhongqiu Wang
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, PR China
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