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Gillson JE, Byeon S, Chou A, Maloney S, Pavlakis N, Clarke SJ, Chan DL, Diakos CI, Gill AJ, Samra JS, Mittal A, Sahni S. Promising biomarker panel to monitor therapeutic efficacy of neoadjuvant chemotherapy in pancreatic cancer patients. Eur J Clin Invest 2025; 55:e14341. [PMID: 39487743 DOI: 10.1111/eci.14341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Accepted: 10/19/2024] [Indexed: 11/04/2024]
Abstract
BACKGROUND Neoadjuvant chemotherapy (NAC) can provide improved survival outcomes in pancreatic ductal adenocarcinoma (PDAC) patients who respond to treatment, but currently available biomarkers cannot reliably predict NAC response. This study aimed to determine the potential of a previously identified diagnostic and prognostic biomarker panel (i.e. Ca-125, S100A2, S100A4, Mesothelin and Ca19-9) for the monitoring of NAC-response in PDAC patients. METHODS This single-centre, retrospective study, utilised serum from NAC treated PDAC patients to determine the levels of biomarkers by Enzyme-Linked Immunosorbent Assay (ELISA). The percentage of the tumour bed occupied by viable carcinoma (PVC) was used to divide patients into good (PVC < 50%) and poor (PVC ≥ 50%) NAC-responders. Statistical analysis was performed to measure the ability of individual biomarkers and a biomarker panel in NAC treatment response and patient survival. RESULTS Serum specimens from a total of 108 PDAC patients were assessed. Ca-125, Ca19-9 and S100A2 showed a significant positive correlation with PVC. Ca-125 demonstrated a superior ability to monitor NAC treatment response (Area under receiver operating curve (AUC): .6954) compared to the more widely used clinical biomarker, Ca19-9 (AUC: .6291). A panel of Ca-125 and Ca19-9 showed good ability to monitor NAC response in PDAC patients (AUC: .7349). Patients with high levels of both Ca-125 and Ca19-9 were shown to have the poorest overall survival (median overall survival: 17 vs. 30 months). CONCLUSION A serum biomarker panel of Ca-125 and Ca19-9 could be used for effective clinical management of PDAC patients undergoing NAC treatment.
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Affiliation(s)
- Josef E Gillson
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia
- Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia
| | - Sooin Byeon
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia
- Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia
| | - Angela Chou
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia
- Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia
- NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia
| | - Sarah Maloney
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia
- Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards, New South Wales, Australia
| | - Nick Pavlakis
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia
- Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards, New South Wales, Australia
| | - Stephen J Clarke
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia
- Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards, New South Wales, Australia
| | - David L Chan
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia
- Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards, New South Wales, Australia
| | - Connie I Diakos
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia
- Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards, New South Wales, Australia
| | - Anthony J Gill
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia
- Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia
- NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia
| | - Jaswinder S Samra
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia
- Australian Pancreatic Centre, St Leonards, Sydney, New South Wales, Australia
- Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, Sydney, New South Wales, Australia
| | - Anubhav Mittal
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia
- Australian Pancreatic Centre, St Leonards, Sydney, New South Wales, Australia
- Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, Sydney, New South Wales, Australia
- The University of Notre Dame Australia, Sydney, New South Wales, Australia
| | - Sumit Sahni
- Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia
- Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia
- Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards, New South Wales, Australia
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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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Sun AH, Zhang XY, Huang YY, Chen L, Wang Q, Jiang XC. Prognostic value and predictive model of tumor markers in stage I to III gastric cancer patients. World J Clin Oncol 2024; 15:1033-1047. [PMID: 39193154 PMCID: PMC11346068 DOI: 10.5306/wjco.v15.i8.1033] [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: 03/20/2024] [Revised: 07/03/2024] [Accepted: 07/24/2024] [Indexed: 08/16/2024] Open
Abstract
BACKGROUND Preoperative serum tumor markers have been widely used in the diagnosis and treatment of gastric cancer patients. However, few studies have evaluated the prognosis of gastric cancer patients by establishing statistical models with multiple serum tumor indicators. AIM To explore the prognostic value and predictive model of tumor markers in stage I and III gastric cancer patients. METHODS From October 2018 to April 2020, a total of 1236 patients with stage I to III gastric cancer after surgery were included in our study. The relationship between serum tumor markers and clinical and pathological data were analyzed. We established a statistical model to predict the prognosis of gastric cancer based on the results of COX regression analysis. Overall survival (OS) was also compared across different stages of gastric cancer. RESULTS The deadline for follow-up was May 31, 2023. A total of 1236 patients were included in our study. Univariate analysis found that age, clinical stage, T and N stage, tumor location, differentiation, Borrmann type, size, and four serum tumor markers were prognostic factors of OS (P < 0.05). It was shown that clinical stage, tumor size, alpha foetoprotein, carcinoembryonic antigen, CA125 and CA19-9 (P < 0.05) were independent prognostic factors for OS. According to the scoring results obtained from the statistical model, we found that patients with high scores had poorer survival time (P < 0.05). Furthermore, in stage I patients, the 3-year OS for scores 0-3 ranged from 96.85%, 95%, 85%, and 80%. In stage II patients, the 3-year OS for scores 0-4 were 88.6%, 76.5%, 90.5%, 65.5% and 60%. For stage III patients, 3-year OS for scores 0-6 were 70.9%, 68.3%, 64.1%, 50.9%, 38.4%, 18.5% and 5.2%. We also analyzed the mean survival of patients with different scores. For stage I patients, the mean OS was 55.980 months. In stage II, the mean OS was 51.550 months. The mean OS for stage III was 39.422 months. CONCLUSION Our statistical model can effectively predict the prognosis of gastric cancer patients.
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Affiliation(s)
- Ai-Hua Sun
- Department of Radiotherapy Oncology, Huizhou Municipal Central Hospital, Huizhou 516001, Guangdong Province, China
| | - Xin-Yu Zhang
- Department of Radiotherapy Oncology, Huizhou Municipal Central Hospital, Huizhou 516001, Guangdong Province, China
| | - Yang-Yang Huang
- Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fuzhou 350001, China
| | - Lei Chen
- Department of General Surgery, Xiang'an Hospital of Xiamen University, Xiamen 361102, Fujian Province, China
| | - Qing Wang
- Department of General Surgery, Xiang'an Hospital of Xiamen University, Xiamen 361102, Fujian Province, China
| | - Xiao-Cong Jiang
- Department of Radiotherapy Oncology, Huizhou Municipal Central Hospital, Huizhou 516001, Guangdong Province, China
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Çaparlar MA, Durhan A, Süleymanov M, Binarbaşı C, Koşmaz K. Prognostic Effect of Preoperative Inflammatory Markers on Morbidity and Overall Survival in Pancreatic Adenocarsinoma. Niger J Clin Pract 2023; 26:1902-1909. [PMID: 38158359 DOI: 10.4103/njcp.njcp_426_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Accepted: 08/14/2023] [Indexed: 01/03/2024]
Abstract
BACKGROUND/AIM His study aimed to evaluate the availability of common diagnostic tests and biochemical markers in predicting poor prognosis in patients with pancreatic adenocarcinoma (PAC). The primary outcome measure was to identify predictive prognostic factors. The secondary outcome measure was to compare predictive measures in patients who survived or did not survive in the follow-up period. MATERIALS AND METHODS Medical data of 51 patients were obtained who underwent resection surgery for PAC between January 2016 and May 2022. There were two groups according to the mortality in the follow-up period group general mortality positive (GMP; n = 29) and group general mortality negative (GMN; n = 22). Stage IIb was the most common stage in subgroups. RESULTS Preoperative diagnostic tests revealed that aspartate aminotransferase (AST) level, De Ritis ratio (DRR), carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA 19-9), immature granulocyte (IG) count, and IG ratio (IG%) are higher, and hemoglobin (Hgb) levels are lower in the GMP group (P < 0.05). In univariate analysis, seven variables, including AST ≥20.5 (P = 0.001), DRR ≥1.05 (P ≤ 0.001), CEA ≥3.32 (P = 0.02), IG count ≥0.06 (P < 0.01), Hgb ≤11.75 (P = 0.01), poor differentiation (P < 0.001) and existence of life-threatening complication (P < 0.01) were identified. In multivariate analysis, only DRR (≥1.05;100% specificity and 72% sensitivity) and poor differentiation (P = 0.019) were found to be independent prognostic factors for overall survival. The median overall survival of patients with the DRR ≥1.05 and poor tumor differentiation was lower, and the mortality rate was higher than the patients with DRR and without poor tumor differentiation (10.65 ± 3.11 months vs. 61.86 ± 5.36 months and 100% vs. 26.7%, P < 0.001). CONCLUSION Pretreatment high DRR, high IG counts and IG%, and poor differentiation of the tumor might be used as independent predictors of poor prognosis and mortality in patients with PAC.
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Affiliation(s)
- M A Çaparlar
- Department of General Surgery, Ankara Education and Research Hospital, Ankara, Turkey
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Zhang LX, Cao ZY, Li HH, Li CH, Li AQ, Luo PQ, Song ED, Wei ZJ, Han WX, Su YZ, Ye LP, Xu AM. Prediction of overall survival after radical gastrectomy using nomograms created by tumor markers. J Investig Med 2023; 71:782-790. [PMID: 37477004 DOI: 10.1177/10815589231179927] [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: 07/22/2023]
Abstract
Prediction of prognosis after radical resection of gastric cancer has not been well established. Therefore, we aimed to establish a prognostic model based on a new score system of patients with gastric cancer. A total of 1235 patients who underwent curative gastrectomy at our hospital from October 2015 to April 2017 were included in this study. Univariate and multivariate analyses were used to screen for prognostic risk factors. Construction of the nomogram was based on Cox proportional hazard regression models. The construction of the new score models was analyzed by the receiver operating characteristic curve (ROC curve), calibration curve, and decision curve. Multivariate analysis showed that tumor size, T, N, carcinoembryonic antigen, CA125, and CA19-9 were independent prognostic factors. The new score model had a greater AUC (The area under the ROC curve) than other systems, and the C-index of the nomogram was highly reliable for evaluating the survival of patients with gastric cancer. Based on the tumor markers and other clinical indicators, we developed a precise model to predict the prognosis of patients with gastric cancer after radical surgery. This score system can be helpful to both surgeons and patients.
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Affiliation(s)
- Li-Xiang Zhang
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
- Department of Gastroenterology, Anhui Provincial Key Laboratory of Digestive Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
| | - Zi-Yi Cao
- Oncology and Hematology Department, Shenzhen Hospital of Shanghai University of Traditional Chinese Medicine, Luohu District, Shenzhen City, Guangdong Province, China
| | - Hao-Hao Li
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
- Department of General Surgery, Anhui Public Health Clinical Center, Anhui, China
| | - Chuan-Hong Li
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Ang-Qing Li
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Pan-Quan Luo
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - En-Dong Song
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Zhi-Jian Wei
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Wen-Xiu Han
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Ye-Zhou Su
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Long-Ping Ye
- Department of Respiratory Medicine, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China
| | - A-Man Xu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
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Liver Tumor Markers, HALP Score, and NLR: Simple, Cost-Effective, Easily Accessible Indexes for Predicting Prognosis in ICC Patients after Surgery. J Pers Med 2022; 12:jpm12122041. [PMID: 36556261 PMCID: PMC9784982 DOI: 10.3390/jpm12122041] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Revised: 12/01/2022] [Accepted: 12/08/2022] [Indexed: 12/14/2022] Open
Abstract
INTRODUCTION To investigate the prognostic significance of liver tumor markers, the hemoglobin, albumin, lymphocyte, and platelet (HALP) score; neutrophil-to-lymphocyte ratio (NLR); and platelet-to-lymphocyte ratio (PLR), for predicting the specific site of recurrence or metastasis after surgery in patients with intrahepatic cholangiocarcinoma (ICC). METHODS In total, 162 patients with pathologically proven ICC who underwent curative surgery at Sun Yat-sen University Cancer Center between April 2016 and April 2020 were analyzed. Clinicopathological characteristics were collected retrospectively. The Kaplan-Meier method was used to analyze the overall survival (OS) and recurrence-free survival (RFS). Significant clinical factors were examined by univariate analysis and multivariate analysis and analyzed by receiver operating characteristic (ROC) curve analysis. RESULTS The cutoff values for the HALP score, NLR, and PLR were determined to be 43.63, 3.73, and 76.51, respectively, using the surv_cutpoint function of survminer using RFS as the target variable. In multivariate analysis, vascular invasion, pathology nerve tract invasion, and carbohydrate antigen 19-9 (CA19-9) levels were independent prognostic factors of OS, whereas the tumor number, pathology microvascular invasion, pathology differentiation, CA19-9 levels, and NLR were independent prognostic factors of RFS. For the whole recurrence analysis, the carcinoembryonic antigen (CEA) index exhibited the largest ROC curve area of all (AUC = 0.590), and the alpha-fetoprotein (AFP) index exhibited the smallest ROC curve area (AUC = 0.530). The HALP score exhibited the largest ROC curve area of all in predicting intrahepatic recurrence (AUC = 0.588), the NLR showed the best predictive value in predicting lymph node metastasis (AUC = 0.703), and the AUC of the CA19-9 index was the largest of all variables in predicting distant metastasis (AUC = 0.619). CONCLUSIONS Our study showed that CA19-9, CEA, HALP score, and NLR are easily accessible, reliable, cost-effective indexes for predicting the specific site of recurrence or metastasis after surgery in ICC patients. Patients with high HALP scores and NLR have a higher risk of intrahepatic and lymph node metastasis recurrence.
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Coppola A, Farolfi T, La Vaccara V, Cammarata R, Caputo D. Role of Neoplastic Markers in Pancreatic Adenocarcinoma. J Clin Med 2022; 11:6509. [PMID: 36362735 PMCID: PMC9653570 DOI: 10.3390/jcm11216509] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 11/01/2022] [Indexed: 01/27/2024] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is considered one of the "Big Five" lethal cancers, which include lung, bowel, breast and prostate cancer [...].
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Affiliation(s)
| | - Tommaso Farolfi
- General Surgery, Università Campus Bio-Medico di Roma, 00128 Rome, Italy
- General Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy
| | - Vincenzo La Vaccara
- General Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy
| | - Roberto Cammarata
- General Surgery, Università Campus Bio-Medico di Roma, 00128 Rome, Italy
| | - Damiano Caputo
- General Surgery, Università Campus Bio-Medico di Roma, 00128 Rome, Italy
- General Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy
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Yunussova N, Sypabekova M, Zhumabekova Z, Matkarimov B, Kanayeva D. A Novel ssDNA Aptamer Targeting Carcinoembryonic Antigen: Selection and Characterization. BIOLOGY 2022; 11:biology11101540. [PMID: 36290442 PMCID: PMC9598387 DOI: 10.3390/biology11101540] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 10/15/2022] [Accepted: 10/17/2022] [Indexed: 11/20/2022]
Abstract
One of the major causes of a drastically shorter life expectancy and one of the most prevalent diseases in the world today is cancer. Given the data on the rise in cancer cases throughout the world, it is obvious that, despite the diagnostic techniques currently being used, there is a pressing need to develop precise and sensitive techniques for early diagnosis of the disease. A high degree of affinity and specificity towards particular targets is maintained by the short nucleic acid molecules known as aptamers. Aptamers outperform antibodies due to their unique benefits, such as their simplicity in synthesis and modification, lack of toxicity, and long-term stability. Utilizing an accurate recognition element and a robust signal transduction mechanism, molecular diagnostics can be extremely sensitive and specific. In this study, development of new single-stranded DNA aptamers against CEA for use in cancer diagnostics was accomplished using SELEX and NGS methods. As a result of 12 iterative SELEX rounds, nine aptamer candidates against CEA were developed. NGS comparative analysis revealed that round twelve had an enriched number of aptamers that were specifically bound, as opposed to round eight. Among the selected nine sequences characterized by bioinformatics analysis and ELONA, an aptamer sequence with the highest specificity and affinity for the target protein was identified and further examined. Aptamer sequence (6) was screened in a concentration-dependent assay, specificity analysis was performed, and its potential secondary and tertiary structures were predicted, which enabled us to test one of the possible putative interactions with CEA. Finally, aptamer sequence (6) labelled with a Cy5 fluorescent tag was used in confocal microscopy to observe its binding towards the CEA expressed in HT-29 human colon adenocarcinoma cell line.
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Affiliation(s)
- Nigara Yunussova
- Ph.D. Program in Life Sciences, Nazarbayev University, 53 Kabanbay Batyr Ave., Astana 010000, Kazakhstan
| | - Marzhan Sypabekova
- National Laboratory Astana, Nazarbayev University, 53 Kabanbay Batyr Ave., Astana 010000, Kazakhstan
| | - Zhazira Zhumabekova
- M.Sc. Program in Biological Sciences, Nazarbayev University, 53 Kabanbay Batyr Ave., Astana 010000, Kazakhstan
| | - Bakhyt Matkarimov
- National Laboratory Astana, Nazarbayev University, 53 Kabanbay Batyr Ave., Astana 010000, Kazakhstan
| | - Damira Kanayeva
- Department of Biology, School of Sciences and Humanities, Nazarbayev University, 53 Kabanbay Batyr Ave., Astana 010000, Kazakhstan
- Correspondence:
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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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Ermiah E, Eddfair M, Abdulrahman O, Elfagieh M, Jebriel A, Al‑Sharif M, Assidi M, Buhmeida A. Prognostic value of serum CEA and CA19‑9 levels in pancreatic ductal adenocarcinoma. Mol Clin Oncol 2022; 17:126. [PMID: 35832472 PMCID: PMC9264325 DOI: 10.3892/mco.2022.2559] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 02/10/2022] [Indexed: 11/10/2022] Open
Abstract
The present study investigated the associations of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels with clinicopathological variables and survival outcomes in Libyan patients with pancreatic ductal adenocarcinoma (PDAC). The clinicopathological variables of 123 patients with PDAC registered at the National Cancer Institute in Misurata, Libya, between 2010 and 2018 were retrospectively analyzed. Blood samples from these patients were analyzed for serum CEA and CA19-9 levels before treatment by electrochemiluminescence immunoassay (double antibody sandwich ELISA) on a Roche cobas e 602 modules. The relationships between CA19-9 and CEA serum levels with clinicopathologic variables and survival outcomes were analyzed using the Kaplan-Meier method, log-rank test and Cox regression analyzes. Cut-off values for serum CEA and CA19-9 levels were 5 ng/ml and 400 U/ml, respectively. The median serum levels of all patients with PDAC for CEA and CA19-9 were 8 ng/ml (1.1-377 ng/ml) and 389 U/ml (1-10,050 U/ml), respectively. Tumors with higher serum CEA and CA19-9 levels were found in 63 and 48% of patients, respectively. Higher CEA and CA19-9 serum levels were significantly associated with more indicators of a malignant phenotype, including a surgically unresectable tumor, unevaluable lymph nodes, advanced stages and distant metastases. Regarding survival, patients with higher serum levels of the biomarkers CEA and CA19-9 had shorter overall survival rates (P<0.016 and (P<0.014, log-rank, respectively) and lower disease-free survival rates (P<0.002 and P<0.0001, log-rank, respectively). The present study demonstrated significant clinical and prognostic value of serum levels of biomarkers CEA and CA19-9 for Libyan patients with PDAC. Moreover, patients with PDAC with higher serum CEA and CA19-9 levels had more aggressive tumors, higher rates of disease recurrence and shorter overall survival rates and thus required more vigilant follow-up. Further multinational studies with larger PDAC cohorts are warranted to confirm these findings in terms of improved clinical decision making, more effective management and improved survival.
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Affiliation(s)
- Eramah Ermiah
- Medical Research Unit, National Cancer Institute, Misurata 051, Libya
| | - Mona Eddfair
- Department of Medical Oncology, National Cancer Institute, Misurata 051, Libya
| | - Othman Abdulrahman
- Department of Medical Oncology, National Cancer Institute, Misurata 051, Libya
| | - Mohamed Elfagieh
- Department of Surgery, National Cancer Institute, Misurata 051, Libya
| | - Abdalla Jebriel
- Department of Medical Oncology, National Cancer Institute, Misurata 051, Libya
| | - Mona Al‑Sharif
- Department of Biology College of Science, University of Jeddah, Jeddah 21589, Saudi Arabia
| | - Mourad Assidi
- Medical Laboratory Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Abdelbaset Buhmeida
- Centre of Excellence in Genomic Medicine Research, King Abdul‑Aziz University, Jeddah 21589, Saudi Arabia
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11
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Zhang J, Zhang Z, Holst S, Blöchl C, Madunic K, Wuhrer M, Ten Dijke P, Zhang T. Transforming growth factor-β challenge alters the N-, O-, and glycosphingolipid glycomes in PaTu-S pancreatic adenocarcinoma cells. J Biol Chem 2022; 298:101717. [PMID: 35151689 PMCID: PMC8914387 DOI: 10.1016/j.jbc.2022.101717] [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: 09/30/2021] [Revised: 01/27/2022] [Accepted: 01/28/2022] [Indexed: 11/13/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor prognosis and high mortality. Transforming growth factor-β (TGF-β) plays a key role in PDAC tumor progression, which is often associated with aberrant glycosylation. However, how PDAC cells respond to TGF-β and the role of glycosylation therein is not well known. Here, we investigated the TGF-β-mediated response and glycosylation changes in the PaTu-8955S (PaTu-S) cell line deficient in SMA-related and MAD-related protein 4 (SMAD4), a signal transducer of the TGF-β signaling. PaTu-S cells responded to TGF-β by upregulating SMAD2 phosphorylation and target gene expression. We found that TGF-β induced expression of the mesenchymal marker N-cadherin but did not significantly affect epithelial marker E-cadherin expression. We also examined differences in N-glycans, O-glycans, and glycosphingolipid-linked glycans in PaTu-S cells upon TGF-β stimulation. TGF-β treatment primarily induced N-glycome aberrations involving elevated levels of branching, core fucosylation, and sialylation in PaTu-S cells, in agreement with TGF-β-induced changes in the expression of glycosylation-associated genes. In addition, we observed differences in O glycosylation and glycosphingolipid glycosylation profiles after TGF-β treatment, including lower levels of sialylated Tn antigen and neoexpression of globosides. Furthermore, the expression of transcription factor sex-determining region Y-related high-mobility group box 4 was upregulated upon TGF-β stimulation, and its depletion blocked TGF-β-induced N-glycomic changes. Thus, TGF-β-induced N-glycosylation changes can occur in a sex-determining region Y-related high-mobility group box 4–dependent and SMAD4-independent manner in the pancreatic PaTu-S cancer cell line. Our results open up avenues to study the relevance of glycosylation in TGF-β signaling in SMAD4-inactivated PDAC.
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Affiliation(s)
- Jing Zhang
- Oncode Institute and Department of Cell Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands
| | - Zejian Zhang
- Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands
| | - Stephanie Holst
- Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands
| | - Constantin Blöchl
- Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands; Department of Biosciences, University of Salzburg, Salzburg, Austria
| | - Katarina Madunic
- Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands
| | - Manfred Wuhrer
- Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands
| | - Peter Ten Dijke
- Oncode Institute and Department of Cell Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands.
| | - Tao Zhang
- Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
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12
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Kang YM, Wang H, Li R, Pan G. Prognostic Role of Carbohydrate Antigen 19 to 9 in Predicting Survival of Patients With Pancreatic Cancer: A Meta-Analysis. Technol Cancer Res Treat 2021; 20:15330338211043030. [PMID: 34617852 PMCID: PMC8642114 DOI: 10.1177/15330338211043030] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
This study evaluates the prognostic role of carbohydrate antigen 19 to 9 (CA19-9) in predicting survival of pancreatic cancer patients. Literature search was conducted in electronic databases (Google Scholar, Ovid, PubMed, and Science Direct) and study selection was based on precise eligibility criteria. Random-effects meta-analyses were performed to achieve overall estimates of median survival and hazard ratios (HRs) of survival with cutoff defined lower and higher CA19-9 levels before and after surgery or chemotherapy (CT)/radiotherapy (RT) and the changes in CA19-9 levels after any treatment. A total of 41 studies (6519 patients; 42% females; age 63.3 years [95% confidence interval [CI]: 62.2, 64.4]) were included. A pooled HR of 1.79 with a narrow 95% CI (1.58, 2.01) showed that higher CA19-9 levels or less decrease in CA19-9 levels after treatment predicted shorter survival. Median survival in patients with lower and higher preoperative CA19-9 levels was 23.2 months [95% CI: 17.2, 29.2] and 14.0 months [95% CI: 10.9, 17.2], respectively, whereas median survival with lower and higher postoperative CA19-9 levels was 25.0 months [95% CI: 21.9, 28.0] and 13.0 months [95% CI: 10.9, 15.0] respectively. Median survival with lower and higher pre-CT/RT CA19-9 levels was 11.9 months [95% CI: 10.2, 13.6] and 7.7 months [95% CI: 6.2, 9.2], respectively, whereas median survival with lower and higher post-CT/RT CA19-9 levels was 15.1 months [95% CI: 13.2, 17.0] and 10.7 months [95% CI: 7.3, 14.0] respectively. A decrease in CA19-9 levels after treatment was also associated with longer survival. Thus, both pretreatment and posttreatment CA19-9 levels or their changes after treatment have good prognostic value in determining the survival of pancreatic cancer patients.
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Affiliation(s)
- Yong-Ming Kang
- 159365Heilongjiang Provincial Hospital, Harbin, Heilongjiang, China
| | - Hao Wang
- Heilongjiang Province Land Reclamation Headquarter General Hospital, Harbin, Heilongjiang, China
| | - Ran Li
- Harbin Red Cross Central Hospital, Harbin, Heilongjiang, China
| | - Gu Pan
- 159365Heilongjiang Provincial Hospital, Harbin, Heilongjiang, China
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13
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Shin K, Jung EK, Park SJ, Jeong S, Kim IH, Lee MA. Neutrophil-to-lymphocyte ratio and carbohydrate antigen 19-9 as prognostic markers for advanced pancreatic cancer patients receiving first-line chemotherapy. World J Gastrointest Oncol 2021; 13:915-928. [PMID: 34457195 PMCID: PMC8371515 DOI: 10.4251/wjgo.v13.i8.915] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 05/03/2021] [Accepted: 07/09/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND A decline in serum carbohydrate antigen 19-9 (CA19-9) levels during systemic chemotherapy is considered as a prognostic marker for patients with advanced pancreatic cancer. Neutrophil-to-lymphocyte ratio (NLR) has been extensively studied as a simple and useful indicator of prognosis in various cancers including pancreatic cancer. AIM To assess the prognostic significance of NLR and CA19-9 in patients with advanced pancreatic adenocarcinoma received first-line chemotherapy according to CA19-9 positivity. METHODS We retrospectively analyzed patients diagnosed with advanced pancreatic cancer who received first-line chemotherapy between January 2010 and July 2017 at the Catholic University of Seoul St. Mary's Hospital. Patients were divided according to CA19-9 positivity (CA19-9-positive vs -negative groups) and pre-and post-treatment NLR levels. To determine cut-off value of NLR and CA19-9 reduction, time-dependent receiver operating characteristic curve was applied. We evaluated overall survival (OS) and progression-free survival (PFS) for each group using Kaplan-Meier method, and we performed multivariate analyses on the entire cohort. RESULTS We included 271 patients in this study. Cut-off value of NLR and CA19-9 reduction was determined as 2.62 and 18%. Multivariate analysis showed that post-treatment NLR < 2.62 and reduction of ≥ 18% of baseline CA19-9 were significantly associated with OS and PFS. Post-treatment NLR ≥ 2.62 showed hazard ratio (HR) of 2.47 [95% confidence interval (CI): 1.84-3.32, P < 0.001] and CA19-9 decline (≥ 18%) showed HR of 0.51 (95%CI: 0.39-0.67, P < 0.001) for OS. When CA19-9-positive patients were divided into groups according to CA19-9 response (responder vs non-responder) and post-treatment NLR (< 2.62 vs ≥ 2.62), CA19-9 responder and post-treatment NLR < 2.62 group showed better survival than CA19-9 non-responder and post-treatment NLR ≥ 2.62 group (OS 11.0 mo vs 3.9 mo, P < 0.001; PFS 6.3 mo vs 2.0 mo, P < 0.001). The combination of CA19-9 decline and post-treatment NLR showed a significant correlation with clinical response in CA 19-9 positive group. Within the CA19-9-negative group, the post-treatment NLR < 2.62 group showed better survival than the post-treatment NLR ≥ 2.62 group (OS 12.7 mo vs 7.7 mo, P < 0.001; PFS 6.7 mo vs 2.1 mo, P < 0.001), and post-treatment NLR showed correlation with clinical response. CONCLUSION In advanced pancreatic cancer patients positive for CA19-9 and treated with systemic chemotherapy, the combination of post-treatment NLR < 2.62 and 18% decline of CA19-9 at the first response evaluation is a good prognostic marker. Post-treatment NLR < 2.62 alone could be used as a prognostic marker and an adjunctive tool for response evaluation in CA19-9-negative patients.
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Affiliation(s)
- Kabsoo Shin
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
- Catholic Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| | - Eun-Kyo Jung
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
- Catholic Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| | - Se Jun Park
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
- Catholic Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| | - Sangwoon Jeong
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
- Catholic Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| | - In-Ho Kim
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
- Catholic Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| | - Myung-ah Lee
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
- Catholic Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
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14
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Yu Y, Zheng P, Chen Y, Wang B, Paul ME, Tao P, Wang D, Li H, Gu B, Gao L, Wang D, Chen H. Advances and challenges of neoadjuvant therapy in pancreatic cancer. Asia Pac J Clin Oncol 2020; 17:425-434. [PMID: 33164329 DOI: 10.1111/ajco.13504] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 07/10/2020] [Indexed: 01/06/2023]
Abstract
Pancreatic cancer has been becoming the second cause of cancer death in the western world, and its disease burden has increased. Neoadjuvant therapy is one of the current research hotspots in the field of pancreatic cancer, aiming to improve the surgical rate and prognosis of pancreatic cancer. Based on the latest evidence, this review discussed neoadjuvant therapy in pancreatic cancer from the following three aspects: patient selection, protocols selection of neoadjuvant therapy, and treatment response evaluation and resectability prediction. A big controversy existed on the indications of neoadjuvant treatment, but it was agreed that any patient who is likely to achieve R0 resection due to neoadjuvant therapy should be the targeted population. A variety of chemotherapy regimens were tried for neoadjuvant therapy in pancreatic cancer, and FOLFIRINOX and Nab-Paclitaxel plus Gemcitabine are two preferred regimens at present. It was challenging to evaluate treatment response and predict resectability after neoadjuvant therapy, although imaging by CT is widely used. Based on new findings of the remarkable performance of several chemotherapy regimens with or without radiotherapy, the neoadjuvant indications of pancreatic cancer have extended in recent years. However, it is still a challenge to assess the neoadjuvant treatment response and determine the timing of surgery.
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Affiliation(s)
- Yang Yu
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, P. R. China.,The Second Clinical Medical College of Lanzhou University, Lanzhou, P. R. China
| | - Peng Zheng
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, P. R. China.,The Second Clinical Medical College of Lanzhou University, Lanzhou, P. R. China
| | - Yajing Chen
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, P. R. China.,The Second Clinical Medical College of Lanzhou University, Lanzhou, P. R. China
| | - Bofang Wang
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, P. R. China.,The Second Clinical Medical College of Lanzhou University, Lanzhou, P. R. China
| | - Maswikiti Ewetse Paul
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, P. R. China.,The Second Clinical Medical College of Lanzhou University, Lanzhou, P. R. China
| | - Pengxian Tao
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, P. R. China.,The Second Clinical Medical College of Lanzhou University, Lanzhou, P. R. China
| | - Dengfeng Wang
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, P. R. China.,The Second Clinical Medical College of Lanzhou University, Lanzhou, P. R. China
| | - Haiyuan Li
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, P. R. China.,The Second Clinical Medical College of Lanzhou University, Lanzhou, P. R. China
| | - Baohong Gu
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, P. R. China.,The Second Clinical Medical College of Lanzhou University, Lanzhou, P. R. China
| | - Lei Gao
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, P. R. China.,The Second Clinical Medical College of Lanzhou University, Lanzhou, P. R. China
| | - Dan Wang
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, P. R. China.,The Second Clinical Medical College of Lanzhou University, Lanzhou, P. R. China
| | - Hao Chen
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, P. R. China.,The Key Laboratory of the Digestive System Tumors of Gansu Province, Lanzhou University Second Hospital, Lanzhou, P. R. China
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15
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van Manen L, Groen JV, Putter H, Pichler M, Vahrmeijer AL, Bonsing BA, Mieog JSD. Stage-Specific Value of Carbohydrate Antigen 19-9 and Carcinoembryonic Antigen Serum Levels on Survival and Recurrence in Pancreatic Cancer: A Single Center Study and Meta-Analysis. Cancers (Basel) 2020; 12:cancers12102970. [PMID: 33066393 PMCID: PMC7602123 DOI: 10.3390/cancers12102970] [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: 09/04/2020] [Revised: 10/12/2020] [Accepted: 10/12/2020] [Indexed: 02/07/2023] Open
Abstract
Simple Summary Pancreatic cancer is one of the most aggressive cancers with a poor survival. Only the minority of patients can be treated by extensive surgery, which is associated with high morbidity. Therefore it could be helpful to identify which patients are at risk of early recurrence and associated poor survival in order to optimize treatment strategies for individual patients. Serum tumor markers, which are readily available and easily implicated in the clinical workflow, are such additional tools. In this study, tumor markers carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) have been studied and results have been compared with existing literature by performing a systematic literature search, as current literature is lacking a complete overview of the prognostic value of both markers. Elevated CA19-9 serum level appear to be an independent prognostic factor for poor survival and early recurrence in pancreatic adenocarcinoma patients, whereas the prognostic value of CEA is disputable. Abstract This study aimed to determine the stage-specific prognostic value of carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) serum levels at diagnosis on overall survival (OS) and time to local recurrence or distant metastases in patients with pancreatic ductal adenocarcinoma (PDAC). Consecutive PDAC patients, discussed at multidisciplinary team meetings from 2013 through 2017, were reviewed. Prognostic factors were stage-specific (resection vs. advanced PDAC) evaluated in Cox proportional hazard models. Additionally, a systematic literature search and meta-analysis was performed, as current literature is lacking a complete overview of used cut-off values and the added value of CEA as prognostic marker. In the retrospective cohort, elevated CA19-9 (>305 kU/L) level was independently associated with poor OS (Hazard ratio (HR): 1.72(1.31–2.26)) and early recurrence (HR: 1.74(1.06–2.86)), whereas CEA was not significantly associated. The meta-analysis showed that both elevated CA19-9 and CEA serum levels were predictors for poor OS (pooled HR: 1.29(1.17–1.42) and HR: 1.51(1.33–1.73), respectively). In the resected cohort, elevated CA19-9 level was significantly associated with early recurrence (pooled HR: 2.41(1.77–3.29)), whereas CEA was not. Elevated CA19-9 serum level appear to be an independent prognostic factor for poor OS and early recurrence in PDAC patients, whereas the prognostic value of CEA is disputable.
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Affiliation(s)
- Labrinus van Manen
- Department of Surgery, Leiden University Medical Center, 2300RC Leiden, The Netherlands; (L.v.M.); (J.V.G.); (A.L.V.); (B.A.B.)
| | - Jesse V. Groen
- Department of Surgery, Leiden University Medical Center, 2300RC Leiden, The Netherlands; (L.v.M.); (J.V.G.); (A.L.V.); (B.A.B.)
| | - Hein Putter
- Department of Medical Statistics, Leiden University Medical Center, 2300RC Leiden, The Netherlands;
| | - Martin Pichler
- Division of Clinical Oncology, Medical University of Graz, 8036 Graz, Austria;
| | - Alexander L. Vahrmeijer
- Department of Surgery, Leiden University Medical Center, 2300RC Leiden, The Netherlands; (L.v.M.); (J.V.G.); (A.L.V.); (B.A.B.)
| | - Bert A. Bonsing
- Department of Surgery, Leiden University Medical Center, 2300RC Leiden, The Netherlands; (L.v.M.); (J.V.G.); (A.L.V.); (B.A.B.)
| | - J. Sven D. Mieog
- Department of Surgery, Leiden University Medical Center, 2300RC Leiden, The Netherlands; (L.v.M.); (J.V.G.); (A.L.V.); (B.A.B.)
- Correspondence: ; Tel.: +31-71-529-9143; Fax: +31-71-526-6770
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16
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van Manen L, Groen JV, Putter H, Vahrmeijer AL, Swijnenburg RJ, Bonsing BA, Mieog JSD. Elevated CEA and CA19-9 serum levels independently predict advanced pancreatic cancer at diagnosis. Biomarkers 2020; 25:186-193. [PMID: 32009482 DOI: 10.1080/1354750x.2020.1725786] [Citation(s) in RCA: 75] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Purpose: It is suggested that tumour markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) could be used to predict the stage of pancreatic cancer. However, optimal cut-off values for CEA and CA19-9 are disputable. This study aimed to assess the value of CEA and CA19-9 serum levels at diagnosis of pancreatic ductal adenocarcinoma (PDAC) as predictors for the advanced stage of PDAC in patients discussed at pancreatic multidisciplinary team (MDT) meetings.Methods: Patients with suspected PDAC discussed at MDT meetings from 2013 to 2017 were reviewed, in order to determine optimal cut-off values of both CEA and CA19-9.Results: In total, 375 patients were included. Optimal cut-off values for predicting advanced PDAC were 7.0 ng/ml for CEA and 305.0 U/ml for CA19-9, resulting in positive predictive values of 83.3%, 73.6%, and 91.4% for CEA, CA19-9 and combined, respectively. Both tumour markers were independent predictors of advanced PDAC, demonstrated by an odds ratio of 4.21 (95% CI:1.85-9.56; p = 0.001) for CEA and 2.58 for CA19-9 (95% CI:1.30-5.14; p = 0.007).Conclusions: CEA appears to be a more robust predictor of advanced PDAC than CA19-9. Implementing CEA and CA19-9 serum levels during MDT meetings as an additional tool for establishing tumour resectability is worthwhile for tailored diagnostics.
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Affiliation(s)
- Labrinus van Manen
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Jesse V Groen
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Hein Putter
- Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands
| | | | | | - Bert A Bonsing
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - J Sven D Mieog
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
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17
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Wu H, Guo JC, Yang SH, Tien YW, Kuo SH. Postoperative Imaging and Tumor Marker Surveillance in Resected Pancreatic Cancer. J Clin Med 2019; 8:1115. [PMID: 31357636 PMCID: PMC6722558 DOI: 10.3390/jcm8081115] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2019] [Revised: 07/05/2019] [Accepted: 07/25/2019] [Indexed: 12/14/2022] Open
Abstract
Background: Pancreatic cancer is a catastrophic disease with high recurrence and death rates, even in early stages. Early detection and early treatment improve survival in many cancer types but have not yet been clearly documented to do so in pancreatic cancer. In this study, we assessed the benefit on survival resulting from different patterns of surveillance in daily practice after curative surgery of early pancreatic cancer. Methods: Patients with pancreatic ductal adenocarcinoma who had received curative surgery between January 2000 and December 2013 at our institute were retrospectively reviewed. Patients were classified into one of four groups, based on surveillance strategy: the symptom group, the imaging group, the marker group (carbohydrate antigen 19-9 and/or carcinoembryonic antigen), and the intense group (both imaging and tumor marker assessment). Overall survival (OS), relapse-free survival (RFS), and post-recurrence overall survival (PROS) were evaluated. Results: One hundred and eighty-one patients with documented recurrence or metastasis were included in our analysis. The median OS for patients in the symptom group, imaging group, marker group, and intense group were 21.4 months, 13.9 months, 20.5 months, and 16.5 months, respectively (p = 0.670). Surveillance with imaging, tumor markers, or both was not an independent risk factor for OS in univariate and multivariate analyses. There was no significant difference in median RFS (symptom group, 11.7 months; imaging group, 6.3 months; marker group, 9.3 months; intense group, 6.9 months; p = 0.259) or median PROS (symptom group, 6.9 months; imaging group, 7.5 months; marker group, 5.0 months; intense group, 7.8 months; p = 0.953) between the four groups. Multivariate analyses identified poor Eastern Cooperative Oncology Group Performance Status (ECOG PS) (≥1), primary tumor site (tail), and tumor grade (poor differentiation) were poor prognostic factors for OS. Conclusions: Surveillance with regular imaging, tumor marker, or both was not an independent risk factor for OS of pancreatic cancer patients who undergo curative tumor resection.
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Affiliation(s)
- Hsu Wu
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
- Department of Oncology, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan
| | - Jhe-Cyuan Guo
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan
- National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Shih-Hung Yang
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yu-Wen Tien
- Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
| | - Sung-Hsin Kuo
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
- Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan.
- National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei, Taiwan.
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan.
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You W, Sheng N, Yan L, Chen H, Gong J, He Z, Zheng K, Chen Z, Wang Y, Tan G, Xie L, Wang Z. The difference in prognosis of stage II and III colorectal cancer based on preoperative serum tumor markers. J Cancer 2019; 10:3757-3766. [PMID: 31333793 PMCID: PMC6636282 DOI: 10.7150/jca.31660] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Accepted: 05/21/2019] [Indexed: 01/20/2023] Open
Abstract
Background: Preoperative serum tumor markers have been widely used to predict prognosis in stage II and III colorectal cancer (CRC). However, few previous studies addressed the effect of increased preoperative numbers of tumor markers. Methods: Patients with stage II and III CRC who underwent curative resection were included from January 2009 to October 2015. The relationship between serum tumor markers and clinicopathological parameters was analyzed. DFS and OS were compared in stage II and III CRC. Results: The median follow-up was 45 months. In this study, 735 enrolled patients were assessed based on the numbers of increased tumor markers. We found that these increased tumor markers were closely associated with clinical stage, T stage, N stage, tumor location, pathology type, differentiation, lymphatic invasion and vascular invasion (all p values < 0.05). Furthermore, the number of increased tumor markers directly affected the survival of patients with CRC after curative surgery. The 3-year DFS and OS of patients with a score of 0 were 84.0% and 91.0%, respectively, which are much higher than those of patients with a score of 4 (42.9% and 37.8%, respectively) (p < 0.05). The 5-year DFS and OS of patients with a score of 0 were 75.9% and 77.9%, respectively, which are much higher than those of patients with a score of 4 (31.7% and 23.6%, respectively). Interestingly, our results suggested that stage III CRC patients with a score of 0 had longer DFS and OS times than stage II patients with scores of 3 and 4. Further analysis revealed statistically significant differences in OS (p < 0.05) but not in DFS. Conclusions: The number of increased tumor markers could significantly predict prognosis in stage II and III CRC. In addition, these increased tumor markers had direct impacts on metastasis as well as the recurrence status and survival time of stage II and III CRC patients.
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Affiliation(s)
- Weiqiang You
- Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
| | - Nengquan Sheng
- Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
| | - Li Yan
- Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
| | - Hongqi Chen
- Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
| | - Jianfeng Gong
- Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
| | - Zhenghui He
- Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Kaiwen Zheng
- Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Zhaohuan Chen
- Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Yafang Wang
- Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Gewen Tan
- Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
| | - Lu Xie
- Shanghai Center for Bioinformation Technology, Shanghai 201203, China
| | - Zhigang Wang
- Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
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Shi S, Yu X. Selecting chemotherapy for pancreatic cancer: Far away or so close? Semin Oncol 2019; 46:39-47. [PMID: 30611527 DOI: 10.1053/j.seminoncol.2018.12.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Revised: 01/26/2018] [Accepted: 12/19/2018] [Indexed: 02/06/2023]
Abstract
Pancreatic cancer is a lethal disease with a very poor prognosis. In contrast to treatments for many other tumor types, cytotoxic agents are still the first-line drugs for pancreatic cancer in both the palliative and adjuvant settings. Some progress has been made in recent years, but most large phase 3 studies have not shown significant improvements in survival. Because the available drugs and regimens are limited in both type and effect, the selection of chemotherapy based on clinicopathologic characteristics may be consequential for pancreatic cancer. In the present report, we focused on 7 landmark clinical trials for pancreatic cancer. We observed that FOLFIRINOX (oxaliplatin, irinotecan, fluorouracil, and leucovorin) and NG (nab-paclitaxel and gemcitabine), 2 first-line regimens, exerted opposite effects on metastatic pancreatic cancer patients with different baseline carbohydrate antigen 19-9 (CA19-9) levels. This suggested that not only the performance status but possibly also CA19-9 levels should be considered when making a therapeutic choice for patients with advanced pancreatic cancer. Moreover, we found that patients with a diagnosis of pancreatic cancer who have undergone a surgical resection with a negative margin (R0) may benefit more from fluorouracil and/or oral prodrugs of fluorouracil-based adjuvant therapy than from gemcitabine. Conversely, gemcitabine or gemcitabine-based regimens may be more effective for patients with a positive resection margin (R1). Based on these findings, we propose flowcharts for selecting chemotherapy for both advanced and resected pancreatic cancer. Furthermore, we present possible mechanisms and interpretations underlying the selection of chemotherapy for pancreatic cancer and propose the tumor burden as a key variable in this process. Regardless of the possible bias and exact treatment selection process, this study offers an opportunity to improve patient outcomes by using agents currently used in the therapy of pancreatic cancer. Although these conclusions are based on indirect evidence, we provide insights and possibilities to drive the selection of chemotherapy for pancreatic cancer.
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Affiliation(s)
- Si Shi
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Pancreatic Cancer Institute, Fudan University, Shanghai, China.
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Zhou X, Wang X, Duan J, Sun W, Chen Z, Li Q, Ou Z, Jiang G, Ren X, Liu S. HBXIP protein overexpression predicts the poor prognosis of pancreatic ductal adenocarcinomas. Pathol Res Pract 2019; 215:343-346. [PMID: 30583814 DOI: 10.1016/j.prp.2018.12.016] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Revised: 11/23/2018] [Accepted: 12/11/2018] [Indexed: 01/17/2023]
Abstract
BACKGROUND Hepatitis B virus X-interacting protein (HBXIP) is associated with a variety of tumors. The purpose of this study was to investigate the clinicopathological significance of HBXIP expression in pancreatic ductal adenocarcinoma (PDAC) and to explore its potential as a biomarker for PDAC. METHODS Immunohistochemical (IHC) staining was performed on 126 PDAC tissues, 36 paraneoplastic tissues and 22 normal pancreatic tissues. The relationship between high levels of HBXIP expression and pathological features of PDAC patients was evaluated by chi-squared values. RESULTS The positive rate of HBXIP protein in PDAC tissues was 85.7% (108/126), which was significantly higher than that of adjacent pancreatic tissue (41.7%, 15/36) and normal pancreas (18.2%, 4/22). In addition, strong positive expression of HBXIP was associated with tumor size, positive lymph node metastasis, clinical stage and 80-month overall survival. Patient's age, gender, degree of differentiation, Ki-67 expression index, and calcification were, however, not associated with high levels of HBXIP expression. CONCLUSIONS We present association between HBXIP expression and the pathological features of patients with PDAC.
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Affiliation(s)
- Xingzhi Zhou
- Department of Pathology, Medical College, Dalian University, Dalian 116622, Liaoning, China; Department of Biology, Life Science and Technology College, Dalian University, Dalian 116622, Liaoning, China
| | - Xuanyu Wang
- Department of Pathology, Medical College, Dalian University, Dalian 116622, Liaoning, China
| | - Jiahong Duan
- Department of Pathology, Medical College, Dalian University, Dalian 116622, Liaoning, China
| | - Wenxin Sun
- Department of Pathology, Medical College, Dalian University, Dalian 116622, Liaoning, China
| | - Zhuo Chen
- Department of Pathology, Medical College, Dalian University, Dalian 116622, Liaoning, China
| | - Qiulan Li
- Department of Pathology, Medical College, Dalian University, Dalian 116622, Liaoning, China
| | - Zitong Ou
- Department of Pathology, Medical College, Dalian University, Dalian 116622, Liaoning, China
| | - Ge Jiang
- Department of Biology, Life Science and Technology College, Dalian University, Dalian 116622, Liaoning, China
| | - Xin Ren
- Department of Pathology, Medical College, Dalian University, Dalian 116622, Liaoning, China.
| | - Shuangping Liu
- Department of clinical laboratory, Xinhua Hospital Affiliated to Dalian University, Dalian, 116021, China; Department of Pathology, Medical College, Dalian University, Dalian 116622, Liaoning, China.
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Schlick K, Magnes T, Ratzinger L, Jaud B, Weiss L, Melchardt T, Greil R, Egle A. Novel models for prediction of benefit and toxicity with FOLFIRINOX treatment of pancreatic cancer using clinically available parameters. PLoS One 2018; 13:e0206688. [PMID: 30412592 PMCID: PMC6226156 DOI: 10.1371/journal.pone.0206688] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2018] [Accepted: 10/17/2018] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Despite modern chemotherapy regimens, survival of pancreatic cancer patients remains dismal. Toxicity is a major concern and it is a challenge to upfront identify patients with the highest benefit from aggressive polychemotherapy. We aimed to evaluate ORR and side effects of the FOLFIRINOX regimen, highlighting dose modification and to explore possible prognostic response factors as a clinical tool. METHODS This retrospective study includes 123 patients with metastatic PC that were treated with FOLFIRINOX between the years 2007 to 2016 in a single academic institution. Survival rates were analysed using the Kaplan-Meier method. Prognostic models including laboratory and clinical parameters were calculated using Cox proportional models in univariate and multivariate analyses. RESULTS Median age at diagnosis was 64 years (47-78 years), 71 (57, 7%) were male and the majority had an ECOG performance status of 0 or 1 (63 patients; 83.7%). After a median follow up of 17.8 months, median progression free survival (PFS) and overall survival (OS) were 5.7 (4.55-6.84; 95%CI) and 11.8 months (9.35-14.24; 95%CI) respectively. Overall response rate with FOLFIRINOX was 34.9% and stable disease rate was 21.9%. Regarding Grade 3/4 side effects, 62 events, were reported in 37 patients. Looking at risk factors e.g. patient characteristics, tumor marker, inflammatory markers and body composition multivariate analyses proved CEA >4 elevation and BMI > 25 at the time point before palliative chemotherapy to be independent negative prognostic factors for OS. Grouping patients with no risk factor, one or two of these risk factors we analyzed a median OS of 17.4 moths, 9.6 months and 6.7 months (p<0.001) respectively. In addition we identified thrombocytosis and low BMI as predictors of early toxicity. CONCLUSION This study identifies two easily available factors influencing overall survival with FOLFIRINOX therapy. By combining these two factors to create a score for OS, we propose a prognostic tool for physicians to identify patients, who are unlikely to benefit more from FOLFIRINOX or likely to experience toxicity.
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Affiliation(s)
- Konstantin Schlick
- IIIrd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Oncologic Center, Paracelsus Medical University, Salzburg, Austria
| | - Teresa Magnes
- IIIrd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Oncologic Center, Paracelsus Medical University, Salzburg, Austria
| | - Lukas Ratzinger
- IIIrd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Oncologic Center, Paracelsus Medical University, Salzburg, Austria
| | - Bernhard Jaud
- IIIrd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Oncologic Center, Paracelsus Medical University, Salzburg, Austria
| | - Lukas Weiss
- IIIrd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Oncologic Center, Paracelsus Medical University, Salzburg, Austria
| | - Thomas Melchardt
- IIIrd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Oncologic Center, Paracelsus Medical University, Salzburg, Austria
| | - Richard Greil
- IIIrd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Oncologic Center, Paracelsus Medical University, Salzburg, Austria
- Salzburg Cancer Research Institute, Salzburg, Austria
- Cancer Cluster Salzburg, Salzburg, Austria
- * E-mail:
| | - Alexander Egle
- IIIrd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Oncologic Center, Paracelsus Medical University, Salzburg, Austria
- Salzburg Cancer Research Institute, Salzburg, Austria
- Cancer Cluster Salzburg, Salzburg, Austria
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Asamer E, Szkandera J, Gibiser P, Lembeck AL, Stojakovic T, Kornprat P, Lackner C, Winder T, Schlick K, Stöger H, Gerger A, Pichler M, Stotz M. Elevated amylase in plasma represents an adverse prognostic marker in patients with metastatic pancreatic cancer : A retrospective analysis. Wien Klin Wochenschr 2018; 130:569-574. [PMID: 30132196 PMCID: PMC6209010 DOI: 10.1007/s00508-018-1383-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2018] [Accepted: 07/31/2018] [Indexed: 01/07/2023]
Abstract
Background and aim The aim of this study was to investigate the prognostic relevance of plasma amylase and lipase concerning survival of patients suffering from metastatic pancreatic cancer (PC). Method This retrospective study included 351 patients with metastatic PC, who were treated in a single academic institution. Cancer-specific survival (CSS) was analyzed using the Kaplan-Meier method. To further evaluate the prognostic significance of lipase and amylase, univariate and multivariate values were calculated using Cox proportional models. Results In univariate analysis, an increased amylase level was associated with shorter CSS in PC patients (hazard ratio HR = 1.258; 95% confidence interval CI = 1.011–1.566; p = 0.039). In multivariate analysis, including gender, age, CA19-9 and administration of chemotherapy, increased amylase levels prevailed as an independent prognostic factor for CSS (HR = 1.373; 95%CI = 1.004–1.878; p = 0.047). Conclusions Plasma amylase was found to be an independent prognostic factor in patients with metastatic PC. The results indicate that amylase might represent a novel and useful marker for better patient stratification in PC management.
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Affiliation(s)
- Eva Asamer
- Division of Clinical Oncology, Department of Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria
| | - Joanna Szkandera
- Division of Clinical Oncology, Department of Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria
| | - Paul Gibiser
- Division of Clinical Oncology, Department of Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria
| | - Anna Lena Lembeck
- Division of Clinical Oncology, Department of Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria
| | - Tatjana Stojakovic
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - Peter Kornprat
- Division of General Surgery, Department of Surgery, Medical University of Graz, Graz, Austria
| | - Caroline Lackner
- Institute of Pathology, Medical University of Graz, Graz, Austria
| | - Thomas Winder
- Department of Oncology, University Hospital Zurich, Zurich, Switzerland
| | - Konstantin Schlick
- 3rd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Paracelsus Medical University, Salzburg, Austria
| | - Herbert Stöger
- Division of Clinical Oncology, Department of Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria
| | - Armin Gerger
- Division of Clinical Oncology, Department of Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.,Research Unit Genetic Epidemiology and Pharmacogenetics, Division of Clinical Oncology, Department of Medicine, Medical University of Graz, Graz, Austria
| | - Martin Pichler
- Division of Clinical Oncology, Department of Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.,Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer, Houston, TX, USA
| | - Michael Stotz
- Division of Clinical Oncology, Department of Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.
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Holst S, Belo AI, Giovannetti E, van Die I, Wuhrer M. Profiling of different pancreatic cancer cells used as models for metastatic behaviour shows large variation in their N-glycosylation. Sci Rep 2017; 7:16623. [PMID: 29192278 PMCID: PMC5709460 DOI: 10.1038/s41598-017-16811-6] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2016] [Accepted: 11/16/2017] [Indexed: 12/18/2022] Open
Abstract
To characterise pancreatic cancer cells from different sources which are used as model systems to study the metastatic behaviour in pancreatic ductal adenocarcinoma (PDAC), we compared the N-glycan imprint of four PDAC cells which were previously shown to differ in their galectin-4 expression and metastatic potential in vivo. Next to the sister cell lines Pa-Tu-8988S and Pa-Tu-8988T, which were isolated from the same liver metastasis of a PDAC, this included two primary PDAC cell cultures, PDAC1 and PDAC2. Additionally, we extended the N-glycan profiling to a normal, immortalized pancreatic duct cell line. Our results revealed major differences in the N-glycosylation of the different PDAC cells as well as compared to the control cell line, suggesting changes of the N-glycosylation in PDAC. The N-glycan profiles of the PDAC cells, however, differed vastly as well and demonstrate the diversity of PDAC model systems, which ultimately affects the interpretation of functional studies. The results from this study form the basis for further biological evaluation of the role of protein glycosylation in PDAC and highlight that conclusions from one cell line cannot be generalised, but should be regarded in the context of the corresponding phenotype.
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Affiliation(s)
- Stephanie Holst
- Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
| | - Ana I Belo
- Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands
| | - Elisa Giovannetti
- Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
- Cancer Pharmacology Lab, AIRC Start-Up Unit, University of Pisa, Pisa, Italy
| | - Irma van Die
- Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands
| | - Manfred Wuhrer
- Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands
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Wen Z, Si A, Yang J, Yang P, Yang X, Liu H, Yan X, Li W, Zhang B. Elevation of CA19-9 and CEA is associated with a poor prognosis in patients with resectable gallbladder carcinoma. HPB (Oxford) 2017; 19:951-956. [PMID: 28750922 DOI: 10.1016/j.hpb.2017.06.011] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2016] [Revised: 06/19/2017] [Accepted: 06/21/2017] [Indexed: 12/12/2022]
Abstract
AIMS The aim of this study was to determine whether a combination of the tumour markers carcinoembryonic (CEA) and carbohydrate antigen 19-9 (CA19-9) would be helpful in predicting the prognosis of patients with gallbladder carcinoma (GBC) who underwent resection. METHODS A retrospective analysis of clinico-pathological features and survival of 390 patients with GBC who were treated between January 2003 and December 2013. Time-dependent receiver operating characteristic (ROC) was used to evaluate the prognostic ability of tumour markers. Combinations of preoperative CEA and CA19-9 were tested as potential prognostic factors. RESULTS The evaluation of preoperative CEA and CA19-9 showed that patients with both tumour markers within the normal range had the best prognosis with a median survival of 27 months and R0 rate of 86%. Patients with both tumour markers elevated had the poorest prognosis and lower R0 rate (p < 0.001). The combination of CEA and CA19-9 was an independent risk factor for overall survival. The AUROC at 5 years of combination of CEA and CA19-9 was 0.798, which was similar to CEA (0.765) or CA19-9 (0.771) alone (p = 0.103, p = 0.147). CONCLUSIONS A combination of an elevated preoperative CEA and CA19-9 was associated with a worse prognosis for patients with GBC who underwent resection.
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Affiliation(s)
- Zhijian Wen
- Department of Biliary Tract Surgery, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China; Department of Hepatobiliary Pancreatic Vascular Surgery, No. 174 Hospital of PLA, Xiamen University, Xiamen, China
| | - Anfeng Si
- Department of Hepatic Surgery IV, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jue Yang
- Department of Biliary Tract Surgery, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Pinghua Yang
- Department of Biliary Tract Surgery, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Xinwei Yang
- Department of Biliary Tract Surgery, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Hu Liu
- Department of Biliary Tract Surgery, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Xingzhou Yan
- Department of Biliary Tract Surgery, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wengang Li
- Department of Hepatobiliary Pancreatic Vascular Surgery, No. 174 Hospital of PLA, Xiamen University, Xiamen, China
| | - Baohua Zhang
- Department of Biliary Tract Surgery, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
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Meng Q, Shi S, Liang C, Liang D, Xu W, Ji S, Zhang B, Ni Q, Xu J, Yu X. Diagnostic and prognostic value of carcinoembryonic antigen in pancreatic cancer: a systematic review and meta-analysis. Onco Targets Ther 2017; 10:4591-4598. [PMID: 28979147 PMCID: PMC5608082 DOI: 10.2147/ott.s145708] [Citation(s) in RCA: 106] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Carcinoembryonic antigen (CEA) is one of the most widely used tumor markers and is increased in 30%-60% of patients with pancreatic cancer. Although carbohydrate antigen 19-9 (CA19-9) is the most important serum biomarker in pancreatic cancer, the diagnostic and prognostic value of CEA is gradually being recognized. MATERIALS AND METHODS The MEDLINE, EMBASE, and Web of Science databases were searched for related literature published until January 2017. Diagnostic accuracy variables were pooled using the Meta-Disc software. The pooled hazard ratios (HRs) for prognostic data were calculated and analyzed using Stata software. RESULTS A total of 3,650 participants enrolled in 19 studies met our inclusion criteria. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of a CEA-based panel were 0.45 (95% confidence interval [CI], 0.41-0.50), 0.89 (95% CI, 0.86-0.91), 5.39 (95% CI, 3.16-9.18), and 0.55 (95% CI, 0.41-0.72), respectively. The area under the curve (AUC, 0.90) and Q-value (0.84) of the CEA-based panel indicated a significantly higher diagnostic accuracy compared with CEA or CA19-9 alone. Moreover, there was also a significant association between high levels of CEA and worse overall survival (HR, 1.43; 95% CI, 1.31-1.56). CONCLUSION Our meta-analysis indicated that elevated serum CEA level, as a vital supplementary to CA19-9, can play an important role in the clinical diagnosis of pancreatic cancer patients and predict poor prognosis.
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Affiliation(s)
- Qingcai Meng
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center
- Department of Oncology, Shanghai Medical College
- Pancreatic Cancer Institute, Fudan University, Shanghai, People’s Republic of China
| | - Si Shi
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center
- Department of Oncology, Shanghai Medical College
- Pancreatic Cancer Institute, Fudan University, Shanghai, People’s Republic of China
| | - Chen Liang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center
- Department of Oncology, Shanghai Medical College
- Pancreatic Cancer Institute, Fudan University, Shanghai, People’s Republic of China
| | - Dingkong Liang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center
- Department of Oncology, Shanghai Medical College
- Pancreatic Cancer Institute, Fudan University, Shanghai, People’s Republic of China
| | - Wenyan Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center
- Department of Oncology, Shanghai Medical College
- Pancreatic Cancer Institute, Fudan University, Shanghai, People’s Republic of China
| | - Shunrong Ji
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center
- Department of Oncology, Shanghai Medical College
- Pancreatic Cancer Institute, Fudan University, Shanghai, People’s Republic of China
| | - Bo Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center
- Department of Oncology, Shanghai Medical College
- Pancreatic Cancer Institute, Fudan University, Shanghai, People’s Republic of China
| | - Quanxing Ni
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center
- Department of Oncology, Shanghai Medical College
- Pancreatic Cancer Institute, Fudan University, Shanghai, People’s Republic of China
| | - Jin Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center
- Department of Oncology, Shanghai Medical College
- Pancreatic Cancer Institute, Fudan University, Shanghai, People’s Republic of China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center
- Department of Oncology, Shanghai Medical College
- Pancreatic Cancer Institute, Fudan University, Shanghai, People’s Republic of China
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Monitoring with sensitive tumor markers contributes to decision-making and better prognosis in gastric cancer patients with peritoneal recurrence. Int J Clin Oncol 2017; 22:897-904. [PMID: 28488013 DOI: 10.1007/s10147-017-1132-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Accepted: 05/02/2017] [Indexed: 01/01/2023]
Abstract
BACKGROUND There is no evidence that monitoring tumor dynamics using sensitive tumor markers contributes to treatment decision-making and prognosis in gastric cancer patients with tumor recurrence. This study was designed to investigate the significance of tumor markers in monitoring peritoneal recurrence of gastric cancer. METHODS We retrospectively analysed 102 consecutive patients who developed recurrence after curative gastrectomy for gastric cancer at our institute between 2002 and 2011. They were followed intensively using tumor markers such as carbohydrate antigen 19-9 and carcinoembryonic antigen. RESULTS Of 102 patients who exhibited recurrence, 51 had peritoneal recurrence. These patients were divided into three groups according to the status of tumor markers at the time of recurrence. Each tumor marker was re-elevated in 28 patients (58%) (re-elevation group; REG), was continuously elevated since initial surgery in 13 patients (22%) (continuous elevation group; CEG) and was not elevated in 10 patients (20%) (non-elevation group; NEG). With regard to survival after recurrence and total postoperative survival, patients in the REG were significantly better than those in the other groups ( p = 0.001, p = 0.018, respectively). REG patients received more different types of chemotherapy regimens than NEG patients because of monitoring (p = 0.018). Multivariate analysis revealed that re-elevation of tumor markers at the time of recurrence was an independent and better prognostic factor for peritoneal recurrence (p = 0.003, hazard ratio 0.29). CONCLUSION Monitoring of tumor dynamics with sensitive tumor markers may contribute to the decision-making process for more promising chemotherapeutic regimens by avoiding subsequent ileus and lead to better prognosis in gastric cancer patients with peritoneal recurrence.
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Luo G, Liu C, Guo M, Cheng H, Lu Y, Jin K, Liu L, Long J, Xu J, Lu R, Ni Q, Yu X. Potential Biomarkers in Lewis Negative Patients With Pancreatic Cancer. Ann Surg 2017; 265:800-805. [PMID: 28267695 DOI: 10.1097/sla.0000000000001741] [Citation(s) in RCA: 120] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
OBJECTIVE To examine potential biomarkers in Lewis negative patients with pancreatic cancer. BACKGROUND Carbohydrate antigen 19-9 (CA19-9) is currently the most important and widely used biomarker in pancreatic cancer. However, approximately 5 to 10% of the population are Lewis negative individuals, and they are documented to have scarce or no CA19-9 secretion. Therefore, it is necessary to explore potential biomarkers to compensate for this drawback. METHODS Lewis genotypes were determined in a large cohort of patients with pancreatic cancer (682 cases) and controls (525 cases) by sequencing the Fucosyltransferase 3 (FUT3) gene from genomic DNA. Potential biomarkers were examined in patients with Lewis negative genotypes and normal subjects. The impact of potential biomarkers on tumor burden and survival was analyzed. RESULTS Forty-seven (6.9%) patients with pancreatic cancer had Lewis negative genotypes. Carcinoembryonic antigen (CEA) and CA125 had greater sensitivity than other biomarkers in Lewis negative patients with pancreatic cancer [CEA, 63.8%; CA125, 51.1%; CA72-4, 25.5%; CA15-3, 21.3%; CA19-9, 19.1%; CA50, 12.8%; CA242, 10.6%; and alpha-fetoprotein (AFP), 0.0%]. In addition, both CEA (98.0%) and CA125 (93.8%) showed a high specificity. Compared with other biomarkers, CEA (60.9%) was sensitive for stage I, II diseases and CA125 (75.0%) was sensitive for stage III, IV diseases. CEA and CA125 were associated with tumor metastasis and therapeutic response. CONCLUSIONS CEA and CA125 have the potential to be applied as biomarkers in Lewis negative patients with pancreatic cancer. CEA and CA125 should be routinely measured for all patients with pancreatic cancer.
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Affiliation(s)
- Guopei Luo
- *Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China†Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China‡Pancreatic Cancer Institute, Fudan University, Shanghai, China§Department of Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China
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C-reactive protein and N-terminal prohormone brain natriuretic peptide as biomarkers in acute exacerbations of COPD leading to hospitalizations. PLoS One 2017; 12:e0174063. [PMID: 28328968 PMCID: PMC5362097 DOI: 10.1371/journal.pone.0174063] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2016] [Accepted: 03/02/2017] [Indexed: 01/02/2023] Open
Abstract
There are currently no accepted and validated blood tests available for diagnosing acute exacerbations of chronic obstructive pulmonary disease (AECOPD). In this study, we sought to determine the discriminatory power of blood C-reactive protein (CRP) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) in the diagnosis of AECOPD requiring hospitalizations. The study cohort consisted of 468 patients recruited in the COPD Rapid Transition Program who were hospitalized with a primary diagnosis of AECOPD, and 110 stable COPD patients who served as controls. Logistic regression was used to build a classification model to separate AECOPD from convalescent or stable COPD patients. Performance was assessed using an independent validation set of patients who were not included in the discovery set. Serum CRP and whole blood NT-proBNP concentrations were highest at the time of hospitalization and progressively decreased over time. Of the 3 classification models, the one with both CRP and NT-proBNP had the highest AUC in discriminating AECOPD (cross-validated AUC of 0.80). These data were replicated in a validation cohort with an AUC of 0.88. A combination of CRP and NT-proBNP can reasonably discriminate AECOPD requiring hospitalization versus clinical stability and can be used to rapidly diagnose patients requiring hospitalization for AECOPD.
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Novel Diagnostic and Predictive Biomarkers in Pancreatic Adenocarcinoma. Int J Mol Sci 2017; 18:ijms18030667. [PMID: 28335509 PMCID: PMC5372679 DOI: 10.3390/ijms18030667] [Citation(s) in RCA: 85] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Revised: 03/07/2017] [Accepted: 03/10/2017] [Indexed: 02/06/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease for a multitude of reasons including very late diagnosis. This in part is due to the lack of understanding of the biological behavior of PDAC and the ineffective screening for this disease. Significant efforts have been dedicated to finding the appropriate serum and imaging biomarkers to help early detection and predict response to treatment of PDAC. Carbohydrate antigen 19-9 (CA 19-9) has been the most validated serum marker and has the highest positive predictive value as a stand-alone marker. When combined with carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA 125), CA 19-9 can help predict the outcome of patients to surgery and chemotherapy. A slew of novel serum markers including multimarker panels as well as genetic and epigenetic materials have potential for early detection of pancreatic cancer, although these remain to be validated in larger trials. Imaging studies may not correlate with elevated serum markers. Critical features for determining PDAC include the presence of a mass, dilated pancreatic duct, and a duct cut-off sign. Features that are indicative of early metastasis includes neurovascular bundle involvement, duodenal invasion, and greater post contrast enhancement. 18-F-fluorodeoxyglucose (18-FDG) radiotracer uptake and changes following treatment may predict patient overall survival following treatment. Similarly, pretreatment apparent diffusion coefficient (ADC) values may predict prognosis with lower ADC lesions having worse outcome. Although these markers have provided significant improvement in the care of pancreatic cancer patients, further advancements can be made with perhaps better combination of markers or discovery of unique marker(s) to pancreatic cancer.
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Conrad TOF, Genzel M, Cvetkovic N, Wulkow N, Leichtle A, Vybiral J, Kutyniok G, Schütte C. Sparse Proteomics Analysis - a compressed sensing-based approach for feature selection and classification of high-dimensional proteomics mass spectrometry data. BMC Bioinformatics 2017; 18:160. [PMID: 28274197 PMCID: PMC5343371 DOI: 10.1186/s12859-017-1565-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2016] [Accepted: 02/24/2017] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND High-throughput proteomics techniques, such as mass spectrometry (MS)-based approaches, produce very high-dimensional data-sets. In a clinical setting one is often interested in how mass spectra differ between patients of different classes, for example spectra from healthy patients vs. spectra from patients having a particular disease. Machine learning algorithms are needed to (a) identify these discriminating features and (b) classify unknown spectra based on this feature set. Since the acquired data is usually noisy, the algorithms should be robust against noise and outliers, while the identified feature set should be as small as possible. RESULTS We present a new algorithm, Sparse Proteomics Analysis (SPA), based on the theory of compressed sensing that allows us to identify a minimal discriminating set of features from mass spectrometry data-sets. We show (1) how our method performs on artificial and real-world data-sets, (2) that its performance is competitive with standard (and widely used) algorithms for analyzing proteomics data, and (3) that it is robust against random and systematic noise. We further demonstrate the applicability of our algorithm to two previously published clinical data-sets.
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Affiliation(s)
- Tim O. F. Conrad
- Department of Mathematics, Freie Universität Berlin, Arnimallee 6, Berlin, Germany
- Zuse Institute Berlin, Takustr. 7, Berlin, Germany
| | - Martin Genzel
- Department of Mathematics, Technische Universität Berlin, Düsternbrooker Weg 20, Berlin, Germany
| | - Nada Cvetkovic
- Department of Mathematics, Freie Universität Berlin, Arnimallee 6, Berlin, Germany
| | - Niklas Wulkow
- Department of Mathematics, Freie Universität Berlin, Arnimallee 6, Berlin, Germany
| | - Alexander Leichtle
- Center of Laboratory Medicine, Inselspital - Bern University Hospital, Düsternbrooker Weg 20, Bern, 24105 Switzerland
| | - Jan Vybiral
- Department of Mathematical Analysis, Charles University, Düsternbrooker Weg 20, Prague, Czech Republic
| | - Gitta Kutyniok
- Department of Mathematics, Technische Universität Berlin, Düsternbrooker Weg 20, Berlin, Germany
| | - Christof Schütte
- Department of Mathematics, Freie Universität Berlin, Arnimallee 6, Berlin, Germany
- Zuse Institute Berlin, Takustr. 7, Berlin, Germany
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Zhou G, Liu X, Wang X, Jin D, Chen Y, Li G, Li C, Fu D, Xu W, Wang X. Combination of preoperative CEA and CA19-9 improves prediction outcomes in patients with resectable pancreatic adenocarcinoma: results from a large follow-up cohort. Onco Targets Ther 2017; 10:1199-1206. [PMID: 28280354 PMCID: PMC5338972 DOI: 10.2147/ott.s116136] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with a 5-year survival rate of <7%. Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) are often used to predict the outcome of the malignancy independently. However, the joint prognostic effect of the two tumor biomarkers has not been well determined. The study assessed the joint role of preoperative CA19-9 and CEA in the prognostic prediction of resectable PDAC in a large cohort of patients. The study enrolled 460 eligible patients who were ready to undergo surgery for PDAC. Restricted cubic spline and direct-adjusted survival curve revealed the nonlinear association between the biomarker levels and prognosis of patients. Combination of preoperative CA19-9 and CEA effectively improved the prognostic prediction. About 100 U/mL of CA19-9 and 10 μg/mL of CEA were revealed as potential assistant index for prognostic prediction in patients with resectable PDAC and may be used as one of the criteria to assess the resectability of PDAC.
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Affiliation(s)
- Guofeng Zhou
- Shanghai Institute of Medical Imaging
- Department of Interventional Radiology, Zhongshan Hospital
| | - Xiaoyu Liu
- Shanghai Institute of Medical Imaging
- Department of Interventional Radiology, Zhongshan Hospital
- Department of Epidemiology, School of Public Health
- Key Laboratory of Public Health Safety, Ministry of Education
| | - Xiaoyi Wang
- Department of Pancreatic Surgery, Institute of Pancreatic Disease, Huashan Hospital
| | - Dayong Jin
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Yi Chen
- Shanghai Institute of Medical Imaging
- Department of Interventional Radiology, Zhongshan Hospital
| | - Guoping Li
- Shanghai Institute of Medical Imaging
- Department of Interventional Radiology, Zhongshan Hospital
| | - Changyu Li
- Shanghai Institute of Medical Imaging
- Department of Interventional Radiology, Zhongshan Hospital
| | - Deliang Fu
- Department of Pancreatic Surgery, Institute of Pancreatic Disease, Huashan Hospital
| | - Wanghong Xu
- Department of Epidemiology, School of Public Health
- Key Laboratory of Public Health Safety, Ministry of Education
| | - Xiaolin Wang
- Shanghai Institute of Medical Imaging
- Department of Interventional Radiology, Zhongshan Hospital
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CA19-9-related tumor kinetics after first-line chemotherapy of patients with advanced pancreatic cancer: a monoinstitutional experience. Med Oncol 2016; 33:103. [PMID: 27522503 DOI: 10.1007/s12032-016-0817-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2016] [Accepted: 08/05/2016] [Indexed: 01/04/2023]
Abstract
The absolute value of carbohydrate antigen 19-9 (CA19-9) pretreatment and its reduction after chemotherapy are established prognostic variables for patients with advanced pancreatic cancer. The present study is a retrospective monoinstitutional evaluation of the prognostic role of the CA19-9 reduction and some CA19-9-related tumor kinetics parameters, such as tumor growth rate constant (G), kinetic tumor response and log ratio. Forty-one cases met the selection criteria. After 8 weeks only G reported an inverse relationship with OS (r = -0.494) that was confirmed by regression analysis (R (2) = 0.192). G after 8 weeks of chemotherapy appears as a possible surrogate end point of overall survival.
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Gu YL, Lan C, Pei H, Yang SN, Liu YF, Xiao LL. Applicative Value of Serum CA19-9, CEA, CA125 and CA242 in Diagnosis and Prognosis for Patients with Pancreatic Cancer Treated by Concurrent Chemoradiotherapy. Asian Pac J Cancer Prev 2016; 16:6569-73. [PMID: 26434876 DOI: 10.7314/apjcp.2015.16.15.6569] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
OBJECTIVE To evaluate the application value of serum CA19-9, CEA, CA125 and CA242 in diagnosis and prognosis of pancreatic cancer cases treated with concurrent chemotherapy. MATERIALS AND METHODS 52 patients with pancreatic cancer, 40 with benign pancreatic diseases and 40 healthy people were selected. The electrochemiluminescence immunoassay method was used for detecting levels of CA19-9, CEA and CA125, and a CanAg CA242 enzyme linked immunoassay kit for assessing the level of CA242. The Kaplan-Meier method was used for analyzing the prognostic factors of patients with pancreatic cancer. The Cox proportional hazard model was applied for analyzing the hazard ratio (HR) and 95% confidential interval (CI) for survival time of patients with pancreatic cancer. RESULTS The levels of serum CA19-9, CEA, CA125 and CA242 in patients with pancreatic cancer were significantly higher than those in patients with benign pancreatic diseases and healthy people (P<0.001). The sensitivity of CA19-9 was the highest among these, followed by CA242, CA125 and CEA. The specificity of CA242 is the highest, followed by CA125, CEA and CA19-9. The sensitivity and specificity of joint detection of serum CA19-9, CEA, CA125and CA242 were 90.4% and 93.8%, obviously higher than single detection of those markers in diagnosis of pancreatic cancer. The median survival time of 52 patients with pancreatic cancer was 10 months (95% CI7.389~12.611).. Patients with the increasing level of serum CA19-9, CEA, CA125, CA242 had shorter survival times (P=0.047. 0.043, 0.0041, 0.029). COX regression analysis showed that CA19-9 was an independent prognostic factor for patients with pancreatic cancer (P=0.001, 95%CI 2.591~38.243). CONCLUSIONS The detection of serum tumor markers (CA19.9, CEA, CA125 and CA242) is conducive to the early diagnosis of pancreatic cancer and joint detection of tumor markers helps improve the diagnostic efficiency. Moreover, CA19-9 is an independent prognostic factor for patients with pancreatic cancer.
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Affiliation(s)
- Yu-Lei Gu
- Emergency Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China E-mail :
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Claire D, Marine G, Aurélie A, Olivier T, Sandrine OT, Flora P, Marc G, Patrice V, Juan I, Jean-Luc R. Heterogeneity of metastatic pancreatic adenocarcinoma: Lung metastasis show better prognosis than liver metastasis-a case control study. Oncotarget 2016; 7:45649-45655. [PMID: 27286454 PMCID: PMC5216749 DOI: 10.18632/oncotarget.9861] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Accepted: 05/08/2016] [Indexed: 12/27/2022] Open
Abstract
The prognosis of metastatic pancreatic ductal adenocarcinoma (PDAC) is grim, with a median overall survival of under 1 year. In our clinical practice, we observed a few cases of isolated lung metastases from PDAC with unusually long outcomes. We compared these cases in a case-control study of lung-only vs. liver-only metastases from PDAC.From our database, we found 37 cases of lung-only metastases and paired them with 37 cases of liver-only metastases by age, tumor location and treatment.The lung-only group differed significantly from the liver-only group with respect to the following parameters: female predominance, more metachronous cases, fewer nodules per patient, and smaller increases in tumor markers. Local invasion parameters (i.e., arterial or venous involvement) were not significantly different. The outcomes were significantly different, with a median overall survival from the occurrence of metastases of 20.8 vs. 9.1 months and a median progression-free survival of 11 vs. 3.5 months.In conclusion, this case-control study seemed to confirm that lung-only PDAC metastases have prognoses different from those of liver-only metastases. A better understanding of the mechanisms underlying these differences will help identify abnormalities associated with tumor aggressiveness.
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Affiliation(s)
- Decoster Claire
- Department of Medical Oncology, Paoli-Calmettes Institute, Marseille 13273, France
| | - Gilabert Marine
- Department of Medical Oncology, Paoli-Calmettes Institute, Marseille 13273, France
| | - Autret Aurélie
- Department of Medical Oncology, Paoli-Calmettes Institute, Marseille 13273, France
- Biostatistic Unit, Paoli-Calmettes Institute, Marseille 13273, France
| | - Turrini Olivier
- Department of Digestive Surgery, Paoli-Calmettes Institute, Marseille 13273, France
| | - Oziel-Taieb Sandrine
- Department of Medical Oncology, Paoli-Calmettes Institute, Marseille 13273, France
| | - Poizat Flora
- Department of Pathology, Paoli-Calmettes Institute, Marseille 13273, France
| | - Giovannini Marc
- Department of Medical Oncology, Paoli-Calmettes Institute, Marseille 13273, France
| | - Viens Patrice
- Department of Medical Oncology, Paoli-Calmettes Institute, Marseille 13273, France
| | - Iovanna Juan
- Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille University and Paoli-Calmettes Institute, Marseille 13273, France
| | - Raoul Jean-Luc
- Department of Medical Oncology, Paoli-Calmettes Institute, Marseille 13273, France
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Pandiaraja J, Viswanathan S, Antomy TB, Thirumuruganand S, Kumaresan DS. The Role of CA19-9 in Predicting Tumour Resectability in Carcinoma Head of Pancreas. J Clin Diagn Res 2016; 10:PC06-9. [PMID: 27134925 DOI: 10.7860/jcdr/2016/17106.7398] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2015] [Accepted: 01/18/2016] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Carbohydrate antigen 19-9 (CA 19-9) is a tumour associated antigen. Blood levels may be elevated in benign as well as malignant conditions. Its sensitivity (70-90%) and specificity (68-91%) are inadequate for accurate diagnosis. It can be used to predict the extent of disease and outcome after resection. AIM The aim of the present study was to assess the role of CA 19-9 in predicting the resectability of the tumour in the head of pancreas. MATERIALS AND METHODS This was a prospective study which included 30 patients and study period was from May 2012 to October 2014. Data collected from all patients with carcinoma of the head of pancreas on the basis of contrast enhanced computed tomography/Magnetic resonance cholangiopancreaticography. CA 19-9 levels were measured and recorded. Patients who were medically unfit for surgery or those who didn't warrant palliative surgery were excluded from the study. During surgery the operative findings on operability were documented and tabulated against corresponding CA 19-9 levels. RESULTS Of the 30 patients who were operated, 13(43.3%) patients had operable tumours and underwent Whipple's procedure and 17(56.7%) underwent palliative bypass procedure. Of the 30, CA 19-9 levels were elevated in 9(30.0%) and were normal in 21(70.0%). Among 13(43.3%) who had operable tumours, CA 19-9 was elevated in 4(13.3) and was normal in 9(30.0%). Of the 17(56.7%) who had inoperable tumours CA 19-9 was elevated in 5(16.7%) and was normal in 12(40.0%). Among the 17 who had inoperable tumours, 8(47.1%) were diagnosed preoperatively and of them CA 19-9 levels were raised in 2(11.8%) and normal in 6(35.3%). In the group of 9(52.9%) who had inoperable tumours diagnosed intraoperatively, CA 19-9 was raised in 3(17.6%) of them and was normal in the remaining 6(35.3%) of them. CONCLUSION Based on the study findings, it can be stated that there is no significant correlation with resectability of pancreatic adenocarcinoma and CA 19-9 and it doesn't predict vascular involvement and liver metastasis.
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Affiliation(s)
- Jayabal Pandiaraja
- Assistant Professor, Department of General Surgery, Srm Medical College and Hospital , Chennai, Tamilnadu, India
| | - Subramanian Viswanathan
- Professor, Department of General Surgery, Govt. Stanley Medical College and Hospital , Chennai, Tamilnadu, India
| | - Thomas Babu Antomy
- Assistant Professor, Department of General Surgery, Govt. Stanley Medical College and Hospital , Chennai, Tamilnadu, India
| | - Sathyamoorthy Thirumuruganand
- Assistant Professor, Department of General Surgery, Govt. Stanley Medical College and Hospital , Chennai, Tamilnadu, India
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Polvani S, Tarocchi M, Tempesti S, Bencini L, Galli A. Peroxisome proliferator activated receptors at the crossroad of obesity, diabetes, and pancreatic cancer. World J Gastroenterol 2016; 22:2441-2459. [PMID: 26937133 PMCID: PMC4768191 DOI: 10.3748/wjg.v22.i8.2441] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2015] [Revised: 12/17/2015] [Accepted: 01/09/2016] [Indexed: 02/06/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the fourth cause of cancer death with an overall survival of 5% at five years. The development of PDAC is characteristically associated to the accumulation of distinctive genetic mutations and is preceded by the exposure to several risk factors. Epidemiology has demonstrated that PDAC risk factors may be non-modifiable risks (sex, age, presence of genetic mutations, ethnicity) and modifiable and co-morbidity factors related to the specific habits and lifestyle. Recently it has become evident that obesity and diabetes are two important modifiable risk factors for PDAC. Obesity and diabetes are complex systemic and intertwined diseases and, over the years, experimental evidence indicate that insulin-resistance, alteration of adipokines, especially leptin and adiponectin, oxidative stress and inflammation may play a role in PDAC. Peroxisome proliferator activated receptor-γ (PPARγ) is a nuclear receptor transcription factor that is implicated in the regulation of metabolism, differentiation and inflammation. PPARγ is a key regulator of adipocytes differentiation, regulates insulin and adipokines production and secretion, may modulate inflammation, and it is implicated in PDAC. PPARγ agonists are used in the treatment of diabetes and oxidative stress-associated diseases and have been evaluated for the treatment of PDAC. PPARγ is at the cross-road of diabetes, obesity, and PDAC and it is an interesting target to pharmacologically prevent PDAC in obese and diabetic patients.
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Han W, Cao F, Chen MB, Lu RZ, Wang HB, Yu M, Shi CT, Ding HZ. Prognostic Value of SPARC in Patients with Pancreatic Cancer: A Systematic Review and Meta-Analysis. PLoS One 2016; 11:e0145803. [PMID: 26731428 PMCID: PMC4701416 DOI: 10.1371/journal.pone.0145803] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Accepted: 12/08/2015] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVE There is a heated debate on whether the prognostic value of SPARC is favorable or unfavorable. Thus, we carried out a meta-analysis evaluating the relationship between SPARC expression and the prognosis of patients with pancreatic cancer. METHODS We searched PubMed, EMBASE and Web of Science for relevant articles. The pooled hazard ratios (HRs) and corresponding 95%CI of overall survival (OS) were calculated to evaluate the prognostic value of SPARC expression in patients with pancreatic cancer. We also performed subgroup analyses. RESULTS With 1623 patients pooled from 10 available studies, the incorporative HR showed an unfavorable prognosis of patients with pancreatic cancer in the multivariate analysis (HR = 1.55, 95%CI: 1.11-2.17, P = 0.01), but not in univariate analysis (HR = 1.41, 95%CI: 0.47-4.21, P = 0.54) and estimate (HR = 1.24, 95%CI: 0.72-2.13, P = 0.44). And this adverse impact could also be found in the subgroup analyses in multivariate analysis, especially in the stroma (HR = 1.53, 95%CI: 1.05-2.24, P = 0.03). However, the combined HR had the highly significant heterogeneity. No obvious publication bias was found. CONCLUSIONS SPARC might be an unfavorable indicator in patients with pancreatic cancer, especially in the stroma. More and further researches should be conducted to reveal the prognostic value of SPARC.
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Affiliation(s)
- Wei Han
- Department of General Surgery, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan Jiangsu, 215300, P. R. China
| | - Fang Cao
- Department of General Surgery, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan Jiangsu, 215300, P. R. China
| | - Min-bin Chen
- Department of Radiotherapy and Oncology, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan Jiangsu, 215300, P. R. China
| | - Rong-zhu Lu
- Department of Preventive Medicine, School of Medicine, Jiangsu University, Zhenjiang Jiangsu, 212001, P. R. China
| | - Hua-bing Wang
- Department of General Surgery, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan Jiangsu, 215300, P. R. China
| | - Min Yu
- Department of General Surgery, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan Jiangsu, 215300, P. R. China
| | - Chun-tao Shi
- Department of General Surgery, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan Jiangsu, 215300, P. R. China
| | - Hou-zhong Ding
- Department of General Surgery, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan Jiangsu, 215300, P. R. China
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Inagaki Y, Song P, Tang W, Kokudo N. Cancer-associated carbohydrate antigens for clinical diagnostic markers--its effectiveness and limitations. Drug Discov Ther 2015; 9:129-32. [PMID: 25994064 DOI: 10.5582/ddt.2015.01031] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Cancer cells express various aberrant glycoconjugates. Several kinds of carbohydrate antigens have been used for the serological tumor markers. In particular, the serological level of sialylated carbohydrate antigens, which contain the sialic acid residue in their structure, showed effectiveness in diagnosing cancer behavior. Although large number of carbohydrate antigens in serum of cancer patients was elevated broadly in various cancers, each tumor marker has different sensitivity and specificity for each cancer. Therefore, the combined use of several tumor markers which have different characteristics is effective for better sensitivity in diagnosing cancer behavior. The mechanism of synthesizing cancer-associated carbohydrate antigens is not fully understood because it is very complex. In addition, new cancer-associated carbohydrate antigens are also identified by molecular oncological studies. Those investigations are considered to develop more effective tumor markers to diagnose cancer behavior.
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Affiliation(s)
- Yoshinori Inagaki
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo
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Guo H, Zhou X, Lu Y, Xie L, Chen Q, Keller ET, Liu Q, Zhou Q, Zhang J. Translational progress on tumor biomarkers. Thorac Cancer 2015; 6:665-71. [PMID: 26557902 PMCID: PMC4632916 DOI: 10.1111/1759-7714.12294] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2015] [Accepted: 06/15/2015] [Indexed: 12/30/2022] Open
Abstract
There is an urgent need to apply basic research achievements to the clinic. In particular, mechanistic studies should be developed by bench researchers, depending upon clinical demands, in order to improve the survival and quality of life of cancer patients. To date, translational medicine has been addressed in cancer biology, particularly in the identification and characterization of novel tumor biomarkers. This review focuses on the recent achievements and clinical application prospects in tumor biomarkers based on translational medicine.
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Affiliation(s)
- Hongwei Guo
- Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education Nanning, China ; Center for Translational Medicine, Guangxi Medical University Nanning, China
| | - Xiaolin Zhou
- Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education Nanning, China ; Center for Translational Medicine, Guangxi Medical University Nanning, China
| | - Yi Lu
- Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education Nanning, China ; Center for Translational Medicine, Guangxi Medical University Nanning, China
| | - Liye Xie
- Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education Nanning, China ; Center for Translational Medicine, Guangxi Medical University Nanning, China
| | - Qian Chen
- Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education Nanning, China ; Center for Translational Medicine, Guangxi Medical University Nanning, China
| | - Evan T Keller
- Department of Urology and Pathology, School of Medicine, University of Michigan Ann Arbor, Michigan, USA
| | - Qian Liu
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital Tianjin, China
| | - Qinghua Zhou
- Lung Cancer Center, Huaxi Hospital, Sichuan University Chengdu, China
| | - Jian Zhang
- Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education Nanning, China ; Center for Translational Medicine, Guangxi Medical University Nanning, China ; Department of Urology and Pathology, School of Medicine, University of Michigan Ann Arbor, Michigan, USA
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Chen F, Guo Y, Wang L. The Emerging Genetic Basis and Its Clinical Implication in Pancreatic Cancer. Gastrointest Tumors 2015. [DOI: 10.1159/000435764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
<b><i>Background:</i></b> Pancreatic cancer is one of the most devastating diseases without early detection, effective screening biomarkers and therapeutic treatments. In the past decades, genetic studies have indicated various genes related to this malignancy. <b><i>Summary:</i></b> Genetic alterations have been involved in the initiation, progression and invasion of pancreatic cancer, which might indicate promising targets for early screening, diagnosis and future intervention. Here we will review genetic changes in pancreatic cancer and analyze their correlations with several common precursors and familial syndromes. <b><i>Key Message:</i></b> Genetic analysis for pancreatic cancer or its precursors might help us to characterize patients into subtype individuals in the future and have significant implications for individualized treatments. <b><i>Practical Implications:</i></b> At present, pancreatic cancer is regarded as a disease with a wide range of genetic alterations, including germline and somatic mutations. Some genetic alterations such as <i>KRAS</i>, <i>p16</i><sup><i>CDKN2A</i></sup>, <i>TP53</i> and <i>SMAD4</i> were specifically correlated with different types of histological precursors of pancreatic cancer and some familial syndromes highly related to pancreatic cancer. Moreover, genetic changes also predict drug sensitivity and implicate novel therapeutic targets.
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