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1
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Yoon JH, Byun HJ, Kim SY, Jung DH, Lee SK. Exosomal LINC00853 promotes progression of gastric cancer via the MAP17/PDZK1/AKT signaling pathway. Noncoding RNA Res 2024; 9:876-886. [PMID: 38586313 PMCID: PMC10997811 DOI: 10.1016/j.ncrna.2024.03.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Revised: 03/26/2024] [Accepted: 03/26/2024] [Indexed: 04/09/2024] Open
Abstract
Although rare, there is ongoing research into biomarkers that predict the onset and recurrence of gastric cancer, particularly focusing on substances found in exosomes. Long non-coding RNAs (lncRNAs) have garnered attention for their potential in diagnosing gastric cancer. This study investigates the role of lncRNAs in gastric cancer, focusing on their presence in exosomes as potential biomarkers for the disease's onset and recurrence. We utilized the ArrayStar Human LncRNA array 2.0 to analyze lncRNA expression in tissues from early-stage gastric cancer patients. Our analysis highlighted LINC00853, which was significantly upregulated in cancer tissues and implicated in promoting epithelial-mesenchymal transition via the MAP17/PDZK1/AKT pathway. Functional studies on AGS and MKN74 gastric cancer cell lines demonstrated that LINC00853 facilitates cell proliferation, invasion, and migration. Additionally, RNA immunoprecipitation and electrophoretic mobility shift assays confirmed LINC00853 interaction with MAP17. Importantly, LINC00853 was also detected in exosomes from both patient samples and cell lines, and its downregulation led to decreased tumorigenicity in AGS cells. These findings suggest that both cellular and exosomal LINC00853 contribute to gastric cancer pathogenesis and may serve as valuable biomarkers for the disease.
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Affiliation(s)
| | | | - Seo Yeon Kim
- Department of Internal Medicine, Yonsei Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
| | - Da Hyun Jung
- Department of Internal Medicine, Yonsei Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
| | - Sang Kil Lee
- Department of Internal Medicine, Yonsei Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
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Zhu Y, Chen H, Wu Y, Jiang T, Wang X, Zheng J, Lin X. Novel nomogram and risk stratification for peritoneal recurrence after curative resection in gastric cancer. Sci Rep 2024; 14:19103. [PMID: 39154083 PMCID: PMC11330521 DOI: 10.1038/s41598-024-70349-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 08/14/2024] [Indexed: 08/19/2024] Open
Abstract
Peritoneal recurrence (PR) in gastric cancer after curative resection has poor prognosis. Therefore, we aimed to construct a nomogram to predict PR, and establish PR score for risk stratification to guide adjuvant chemotherapy. A total of 315 patients with gastric cancer after radical surgery were included, and randomly stratified into training group (n = 221) and validation group (n = 94). Univariate and multivariate analyses were used to determine predictive factors of PR. The nomogram was constructed to predict the risk of PR. We utilized the time-dependent area under the receiver operating characteristic (ROC) curves (AUCs), calibration curves, and decision curve analysis (DCA) to evaluate the performance of the nomogram. Multivariate analysis showed that tumor site, N stage, preoperative CEA, and postoperative CA199 were independent predictors of PR. A nomogram was constructed to predict PR based on these factors. The AUC value was 0.755 in the training group and 0.715 in the validation group. The calibration curves showed good agreement between prediction and observation in the training and validation groups. The decision curve analysis displayed a good net benefit of the nomogram. The novel PR score was developed and patients were stratified into the low-, medium-, and high -risk groups. For the high-risk group, postoperative adjuvant chemotherapy significantly improved patients' overall survival (OS) and disease-free survival (DFS). The establishment of nomogram facilitates the prediction of PR after radical gastrectomy, and a novel PR score may help guide adjuvant chemotherapy for gastric cancer.
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Affiliation(s)
- Yingjiao Zhu
- Department of Medical Oncology, Fujian Medical University Union Hospital, No. 29 Xinquan Street, Fuzhou, 350001, Fujian, China
| | - Hao Chen
- Department of Medical Oncology, Fujian Medical University Union Hospital, No. 29 Xinquan Street, Fuzhou, 350001, Fujian, China
| | - Yahua Wu
- Department of Medical Oncology, Fujian Medical University Union Hospital, No. 29 Xinquan Street, Fuzhou, 350001, Fujian, China
| | - Tao Jiang
- Department of Medical Oncology, Fujian Medical University Union Hospital, No. 29 Xinquan Street, Fuzhou, 350001, Fujian, China
| | - Xinli Wang
- Department of Medical Oncology, Fujian Medical University Union Hospital, No. 29 Xinquan Street, Fuzhou, 350001, Fujian, China
| | - Jianwei Zheng
- Department of Medical Oncology, Fujian Medical University Union Hospital, No. 29 Xinquan Street, Fuzhou, 350001, Fujian, China
| | - Xiaoyan Lin
- Department of Medical Oncology, Fujian Medical University Union Hospital, No. 29 Xinquan Street, Fuzhou, 350001, Fujian, China.
- Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, Fujian, China.
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Zhou Y, Tao L, Qiu J, Xu J, Yang X, Zhang Y, Tian X, Guan X, Cen X, Zhao Y. Tumor biomarkers for diagnosis, prognosis and targeted therapy. Signal Transduct Target Ther 2024; 9:132. [PMID: 38763973 PMCID: PMC11102923 DOI: 10.1038/s41392-024-01823-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 03/07/2024] [Accepted: 04/02/2024] [Indexed: 05/21/2024] Open
Abstract
Tumor biomarkers, the substances which are produced by tumors or the body's responses to tumors during tumorigenesis and progression, have been demonstrated to possess critical and encouraging value in screening and early diagnosis, prognosis prediction, recurrence detection, and therapeutic efficacy monitoring of cancers. Over the past decades, continuous progress has been made in exploring and discovering novel, sensitive, specific, and accurate tumor biomarkers, which has significantly promoted personalized medicine and improved the outcomes of cancer patients, especially advances in molecular biology technologies developed for the detection of tumor biomarkers. Herein, we summarize the discovery and development of tumor biomarkers, including the history of tumor biomarkers, the conventional and innovative technologies used for biomarker discovery and detection, the classification of tumor biomarkers based on tissue origins, and the application of tumor biomarkers in clinical cancer management. In particular, we highlight the recent advancements in biomarker-based anticancer-targeted therapies which are emerging as breakthroughs and promising cancer therapeutic strategies. We also discuss limitations and challenges that need to be addressed and provide insights and perspectives to turn challenges into opportunities in this field. Collectively, the discovery and application of multiple tumor biomarkers emphasized in this review may provide guidance on improved precision medicine, broaden horizons in future research directions, and expedite the clinical classification of cancer patients according to their molecular biomarkers rather than organs of origin.
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Affiliation(s)
- Yue Zhou
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Lei Tao
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Jiahao Qiu
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Jing Xu
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xinyu Yang
- West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Yu Zhang
- West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
- School of Medicine, Tibet University, Lhasa, 850000, China
| | - Xinyu Tian
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xinqi Guan
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xiaobo Cen
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
- National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Yinglan Zhao
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
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Demiryas S, Orhan A. Advancements in Gastrointestinal System Biomarkers. Biomark Med 2022. [DOI: 10.2174/9789815040463122010016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
The requirement for diagnostic surgical operations of gastrointestinal system
diseases significantly decreases with the help of proper diagnostic tools. These
modalities are also beneficial for identifying postoperative complications, allowing us
to diagnose them in earlier stages, and increasing the postoperative survival rates.
Biomarkers are considered an integral part of diagnostic examinations. Developments
of biomarkers used for diagnosing and treating abdominal diseases are essential for
improving our capabilities in non-invasive monitoring. In this chapter, we review both
the novel and the routine biomarkers in the diagnosis and follow-up of gastrointestinal
system diseases.
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Affiliation(s)
- Suleyman Demiryas
- Department of General Surgery, Cerrahpaşa School of Medicine, IIstanbul University –
Cerrahpaşa, Istanbul, Turkey
| | - Anıl Orhan
- Department of General Surgery, Haseki Training and Research Hospital, University of Health
Sciences, Istanbul, Turkey
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Huang B, Rouvelas I, Nilsson M. Gastric and gastroesophageal junction cancer: Risk factors and prophylactic treatments for prevention of peritoneal recurrence after curative intent surgery. Ann Gastroenterol Surg 2022; 6:474-485. [PMID: 35847435 PMCID: PMC9271029 DOI: 10.1002/ags3.12565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 02/13/2022] [Accepted: 03/01/2022] [Indexed: 11/08/2022] Open
Abstract
Aim Relapse after curative treatment for advanced gastric cancer, and especially peritoneal recurrence, is very common and has a dismal prognosis. The aim of this review is to summarize existing evidence regarding risk factors and prophylactic treatments intending to prevent peritoneal recurrence. Methods A structured search of relevant studies was conducted in MEDLINE, Embase, and the Cochrane Library. Results The main risk factors identified are advanced pathological T-stage (pT ≥ 3), regional lymph node involvement, diffuse/poorly cohesive type tumor, poorly differentiated cancer, and positive peritoneal wash cytology. Systemic chemotherapy in the perioperative or adjuvant setting improves survival for the patients but despite this peritoneal recurrence remains a common and yet an unsolved clinical problem. Different approaches of intraperitoneal chemotherapy such as hyperthermic intraperitoneal chemotherapy and early postoperative intraperitoneal chemotherapy have shown promising results as prophylactic treatments aiming to prevent peritoneal recurrence. Conclusion Future studies are warranted to find safe and effective treatments to prevent peritoneal recurrence.
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Affiliation(s)
- Biying Huang
- Department of Upper Abdominal DiseasesKarolinska University HospitalStockholmSweden
| | - Ioannis Rouvelas
- Department of Upper Abdominal DiseasesKarolinska University HospitalStockholmSweden
- Division of SurgeryDepartment of Clinical Science, Intervention and Technology (CLINTEC)Karolinska InstitutetStockholmSweden
| | - Magnus Nilsson
- Department of Upper Abdominal DiseasesKarolinska University HospitalStockholmSweden
- Division of SurgeryDepartment of Clinical Science, Intervention and Technology (CLINTEC)Karolinska InstitutetStockholmSweden
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Shibata C, Nakano T, Yasumoto A, Mitamura A, Sawada K, Ogawa H, Miura T, Ise I, Takami K, Yamamoto K, Katayose Y. Comparison of CEA and CA19-9 as a predictive factor for recurrence after curative gastrectomy in gastric cancer. BMC Surg 2022; 22:213. [PMID: 35655198 PMCID: PMC9164336 DOI: 10.1186/s12893-022-01667-z] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 05/25/2022] [Indexed: 12/27/2022] Open
Abstract
Background Our aim of was to compare importance of the tumor markers (TMs) serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 in prediction of recurrence after curative gastrectomy for gastric cancer. Methods We reviewed retrospectively the clinical records of 149 patients who underwent curative gastrectomy for stage I–III gastric cancer and whose CEA and CA19-9 levels were determined once preoperatively and for more than 3 years postoperatively. We investigated whether the clinicopathological characteristics of patients including age, sex, pathological disease stage, operative approach, type of gastrectomy, and degree of lymph node dissection as well as preoperative positivity of CEA and CA19-9 were risk factors for recurrence in univariate and multivariate analyses. Rate of recurrence was compared between patients positive and negative for postoperative CEA or CA19-9. We also calculated sensitivity, specificity, positive and negative predictable values of postoperative positivity of CEA and CA19-9 for recurrence. The lead time was compared between CEA and CA19-9 that was defined as the time of the first detection of increases in tumor markers and confirmation of recurrence on imaging modalities. Results The number of patients positive for preoperative CEA was 25 (17%) and for CA19-9 was 11 (7%). Recurrence was confirmed in 29 (19%) patients. Stage III disease, preoperative positivity for CA19-9 but not CEA, and total gastrectomy were risk factors for recurrence in univariate analysis, but stage III disease was the only risk factor for recurrence in multivariate analysis. Forty and 15 patients were positive for postoperative CEA and CA19-9, respectively. The recurrence rate of 47% (7/15) in patients positive for postoperative CA19-9 was greater than that in negative patients (22/134 = 16%), but it did not differ between patients who were positive or negative for postoperative CEA. Specificity for CA19-9 was greater than that for CEA (P < 0.05). The lead time of CEA (3.9 ± 4.7 months) was not different from that of CA19-9 (6.1 ± 7.1 months). Conclusions These results indicate that CA19-9 rather than CEA is likely to be more useful for the detection of recurrence after curative gastrectomy for gastric cancer.
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Noh J, Park KB, Kwon OK. The prognostic value of postoperative tumor marker conversion for gastric cancer. KOREAN JOURNAL OF CLINICAL ONCOLOGY 2020; 16:119-126. [PMID: 36945721 PMCID: PMC9942728 DOI: 10.14216/kjco.20018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Revised: 09/20/2020] [Accepted: 10/19/2020] [Indexed: 11/07/2022]
Abstract
Purpose Preoperative positivity of serum tumor markers has been associated with poor long-term survival among patients with gastric cancer. However, there have been a considerable number of patients who have experienced a normalization of tumor markers (negative conversion) after curative treatment. This study aimed to evaluate the correlation between postoperative tumor marker conversion and survival after gastrectomy among gastric carcinoma patients. Methods We analyzed the clinical data of 129 patients who underwent curative gastrectomy with elevated preoperative carcinoembryonic antigen or carbohydrate antigen 19-9 between January 2009 and December 2013. Results Positive tumor markers converted to negative markers 6 months after surgery in 91 patients (70.5%). The patients with a negative conversion of tumor markers had significantly better outcomes than those without negative conversion (overall survival [OS] 63.9 months vs. 41.1 months, P<0.001; disease-free survival [DFS] 59.3 months vs. 33.2 months, P<0.001). Multivariate analyses showed that tumor marker conversion and lymph node metastasis were independent predictors of OS and DFS. During follow-up, tumor markers became elevated again (positive reconversion) in 23 patients (25.3%), with a negative conversion of tumor markers at 6 months after gastrectomy. Among the patients with a positive reconversion of tumor markers, gastric cancer recurred in 18 patients (78.3%). Conclusion Negative tumor marker conversion after curative gastrectomy strongly predicts a better prognosis. Patients without negative tumor marker conversion and those with positive reconversion after normalization should be carefully monitored because of the high possibility of recurrence.
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Affiliation(s)
- Jeongju Noh
- Department of Surgery, Kyungpook National University Hospital, Daegu, Korea
| | - Ki Bum Park
- Department of Surgery, School of Medicine, Kyungpook National University, Daegu, Korea
- Gastric Cancer Center, Kyungpook National University Chilgok Hospital, Daegu, Korea
| | - Oh Kyoung Kwon
- Department of Surgery, School of Medicine, Kyungpook National University, Daegu, Korea
- Gastric Cancer Center, Kyungpook National University Chilgok Hospital, Daegu, Korea
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8
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Song XH, Liu K, Yang SJ, Zhang WH, Chen XL, Zhao LY, Chen XZ, Yang K, Zhou ZG, Hu JK. Prognostic Value of Changes in Preoperative and Postoperative Serum CA19-9 Levels in Gastric Cancer. Front Oncol 2020; 10:1432. [PMID: 33014781 PMCID: PMC7461783 DOI: 10.3389/fonc.2020.01432] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Accepted: 07/07/2020] [Indexed: 02/05/2023] Open
Abstract
Objective: The prognostic significance of serum CA19-9 levels in gastric cancer patients remains a matter debate. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative serum CA19-9 levels in patients with gastric cancer. Methods: A total of 1,046 gastric cancer patients who underwent curative gastrectomy in West China Hospital of Sichuan University from January 2011 to December 2016 were analyzed retrospectively. Patients were categorized by minimum P-value using X-tile, while the baseline confounders for CA19-9 changes were balanced through propensity score matching (PSM). The relationships between CA19-9 changes and other clinicopathologic features were measured. Univariate and multivariate analysis were performed to explore the risk factors associated with survival outcomes. Results: We included 653 patients. Changes in CA19-9 levels significantly correlated with age, tumor size, macroscopic type, histological grade, T stage and TNM stage. Kaplan-Meier curves revealed that patients with CA19-9 changes <20% had significant better overall survival than those with changes more than 20% (p < 0.001); Cox regression analysis revealed the CA19-9 change (p = 0.010), gender (p = 0.031), histological grade (p = 0.036) and TNM stage (p < 0.001) were independent risk factors for survival after PSM. Stratification analysis indicated that patients with CA19-9 change more than 20% had worse prognosis that those with CA19-9 change no more than 20% in male (p = 0.002), poorly differentiated or undifferentiated type (p = 0.031) and TNM stage III (p = 0.006). Conclusion: Changes in preoperative and postoperative serum CA19-9 levels were closely associated with clinicopathological traits and was an independent prognostic factor in gastric cancer patients. This parameter may be a reliable marker for prediction of survival.
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Affiliation(s)
- Xiao-Hai Song
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Kai Liu
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Shi-Jie Yang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Wei-Han Zhang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Xiao-Long Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Lin-Yong Zhao
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Xin-Zu Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Kun Yang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Zong-Guang Zhou
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Digestive Surgery, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Jian-Kun Hu
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
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Can Preoperative Examination Help Choose the Best Surgical Procedure in Gastric Cancer? Gastroenterol Res Pract 2018; 2018:4914201. [PMID: 29805443 PMCID: PMC5901933 DOI: 10.1155/2018/4914201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2017] [Accepted: 03/13/2018] [Indexed: 11/17/2022] Open
Abstract
Aim Gastrectomy with lymph node dissection is standard treatment in gastric cancer. This study aimed to explore whether preoperative investigation finds could predict lymph node metastatic scope in gastric carcinoma so that the optimal surgical procedure could be selected. Materials and Methods Radical gastrectomy patients (n = 378) were separated into two groups according to the lymph node metastatic scope. Univariate and multivariate analyses of preoperative examination results were performed to identify the predictors of metastatic scope. ROC curves were constructed, and the area under the curve (AUC) was calculated to estimate diagnostic values. Results Serum CEA (OR: 3.73; 95% CI: 1.84–7.56; P ≤ 0.001), tumor size (OR: 2.07; 95% CI: 1.08–3.98; P = 0.03), and CT examination results (OR: 17.81; 95% CI: 9.18–34.55; P ≤ 0.001) were identified as independent predictors. The AUC proved that they possessed significant diagnostic value. When CT examination was negative, the combination of serum CEA and tumor size showed high specificity (95.3%; 164/172), negative predictive value (92.7%; 164/177), and accuracy (89.0%; 170/191). Conclusions Preoperative serum CEA, tumor size, and CT examination are independent predictors of lymph node metastatic scope and can be used for selecting the appropriate lymphadenectomy pattern in gastric cancer patients.
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Kotzev AI, Draganov PV. Carbohydrate Antigen 19-9, Carcinoembryonic Antigen, and Carbohydrate Antigen 72-4 in Gastric Cancer: Is the Old Band Still Playing? Gastrointest Tumors 2018; 5:1-13. [PMID: 30574476 DOI: 10.1159/000488240] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 03/08/2018] [Indexed: 12/12/2022] Open
Abstract
Background Gastric cancer (GC) is characterized by aggressive behavior and a high mortality rate. The diagnosis of GC is challenging because the GC is often diagnosed in an advanced stage. The use of tumor markers is a putative way to improve the detection and treatment in patients with GC. Summary In this article, we review the significance of serum carbohydrate antigen (CA) 19-9, carcinoembryonic antigen (CEA), and CA 72-4 in GC. The results from different studies regarding the diagnostic and prognostic role of CA 19-9, CEA, and CA 72-4 in GC are encouraging, but inadequate sensitivity and specificity obstruct their use as standardized and unconditionally reliable markers in GC. New prospective clinical trials are mandatory for clarifying their value in GC. Key Message CA 19-9, CEA, and CA 72-4 should not be used for screening and early diagnosis in GC, whereas they are beneficial in the detection of late GC. CA 19-9, CEA, and CA 72-4 could be used as prognostic and monitoring tools in GC, and their combined measurement in shorter periods of time is the best method to increase sensitivity and specificity. Practical Implications Serum CA 19-9, CEA, and CA 72-4 are useful diagnostic and prognostic tumor markers in GC.
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Affiliation(s)
- Andrey Iskrenov Kotzev
- Clinic of Gastroenterology, University Hospital "Alexandrovska," Medical University Sofia, Sofia, Bulgaria
| | - Peter Vassilev Draganov
- Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, Florida, USA
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11
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Hasbahceci M, Malya FU, Kunduz E, Guler M, Unver N, Akcakaya A. Use of serum and peritoneal CEA and CA19-9 in prediction of peritoneal dissemination and survival of gastric adenocarcinoma patients: are they prognostic factors? Ann R Coll Surg Engl 2018; 100:257-266. [PMID: 29543051 PMCID: PMC5958855 DOI: 10.1308/rcsann.2018.0011] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/07/2017] [Indexed: 12/19/2022] Open
Abstract
Introduction To evaluate the impact of serum and peritoneal levels of tumour markers on peritoneal carcinomatosis and survival in gastric adenocarcinoma. Materials and methods Patients with gastric adenocarcinoma were evaluated with regard to serum and peritoneal carcinoembryonic antigen (CEA) and CA19-9. Numeric values and groupings based on serum and peritoneal cutoff values were used. Development of peritoneal carcinomatosis, including positive washing cytology, was regarded as main outcome. Gastric cancer outcomes as disease free and overall survival were analysed. Results There were 67 patients with a mean age of 60 ± 11 years. Positive peritoneal washing cytology was significantly associated with serum CA19-9 and high serum CA 19-9 group (P = 0.033 and P = 0.011, respectively). High peritoneal CEA was shown to be significantly associated with peritoneal carcinomatosis (P = 0.032). After a median follow up of 17 months, 48 patients (71.7%) were alive. Patients with peritoneal carcinomatosis showed significant poorer prognosis as shown by overall survival rate of 28.6%. Only serum CEA was significantly associated with lower disease free and overall survival (P = 0.002 and P = 0.001, respectively). Discussion and conclusion Serum CEA is shown to be significantly associated with poor prognosis for gastric cancer patients. Serum level of CA19-9 and high peritoneal CEA levels are significant predictors for positive peritoneal washing cytology and the development of peritoneal carcinomatosis, respectively. Therefore, the possible impact of serum and peritoneal tumor markers especially on the staging and prognosis of gastric cancer remains to be clarified by future studies.
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Affiliation(s)
- M Hasbahceci
- Medical Park Group, Fatih Hospital, General Surgery Clinic, Fatih, Istanbul, Turkey
| | - FU Malya
- Department of General Surgery, Faculty of Medicine, Bezmialem Vakif University, Fatih, Istanbul, Turkey
| | - E Kunduz
- Department of General Surgery, Faculty of Medicine, Bezmialem Vakif University, Fatih, Istanbul, Turkey
| | - M Guler
- Department of General Surgery, Faculty of Medicine, Bezmialem Vakif University, Fatih, Istanbul, Turkey
| | - N Unver
- Department of Pathology, Faculty of Medicine, Bezmialem Vakif University, Fatih, Istanbul, Turkey
| | - A Akcakaya
- Department of General Surgery, Faculty of Medicine, Bezmialem Vakif University, Fatih, Istanbul, Turkey
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12
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Clinical Assessment and Prognostic Evaluation of Tumor Markers in Patients with Gastric Cancer. Int J Biol Markers 2018; 28:192-200. [PMID: 23787496 DOI: 10.5301/jbm.5000023] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/11/2013] [Indexed: 12/27/2022]
Abstract
Aim To investigate the relationship between the serum levels of CEA, CA19-9, CA24-2, CA72-4, and AFP in patients with gastric cancer (GC) and their clinicopathological characteristics; to analyze the efficacy of these tumor markers in evaluating the prognosis of GC. Methods Overall, 389 patients with GC either located in the gastric cardia (132), the pyloric antrum (112) or the body of the stomach (145) were included in the study. Serum levels of CEA, CA19-9, CA72-4, and AFP were detected with the ECLIA method, while CA24-2 was measured with ELISA. Results First, the serum level of CEA in GC patients with a cardia-located cancer was significantly higher than in patients with pyloric antrum-located cancer (p=0.050). CA72-4 level in patients with GC located in the gastric body was significantly higher than in patients with cardia and pyloric antrum-located cancers (p=0.042 and p=0.039, respectively). Secondly, serum CA19-9 and CA24-2 levels in females with cardia-located GC were significantly higher than those in males with the same type of tumor (p=0.037 and p=0.033, respectively). Additionally, for females with gastric body-located GC the levels of CEA and CA72-4 were significantly higher than those in male patients with the same type of tumor (p=0.047 and p=0.048, respectively). Conversely, in female GC patients with pyloric antrum-located cancer the serum levels of CA19-9 and CA24-2 were significantly lower than those in male patients with the same type of cancer (p=0.013 and p=0.007, respectively). Moreover, CEA, CA19-9, CA24-2, and CA72-4 levels were strongly related to TNM grade and histological anatomy stage, whereas CEA and CA72-4 levels were strongly related to lymph node stage (p=0.000 and p=0.042, respectively). Patients with vascular embolism had higher serum levels of CEA, CA19-9, CA24-2, and CA72-4 compared with patients without vascular embolism (p=0.005, p=0.031, p=0.007, and p=0.014, respectively). In patients with distant metastases and ascites the levels of CEA, CA19-9, and CA24-2 were higher than in patients without these conditions (p=0.003, p=0.001, p=0.001, p=0.016, p= 0.011, and p=0.030, respectively). Serum CEA, CA19-9, and CA24-2 levels showed correlations with tumor invasive depth and growth types (p=0.001, p=0.040, and p=0.035, respectively). Patients with lump and catheter tumor growth types had significantly higher AFP levels than patients with invasion and anabrosis growth types (p=0.034 and p=0.005, respectively). Tumor size was correlated with the preoperative serum levels of CEA, AFP, and CA72-4 (p=0.007, p=0.020, and p=0.008, respectively). Additionally multiple linear regression analysis showed that preoperative levels of CEA and CA72-4 were correlated to TNM stages, CA19-9 and CA24-2 levels were correlated to both gender and distant metastasis, and AFP was correlated only to ascites. During follow-up there were 115 deaths. Median survival time for GC patients with negative preoperative CEA was 18.07 months, and was 10.97 months for patients with preoperative CEA positive levels (p=0.0005). Similarly, the median survival time for GC patients with negative preoperative CA72-4 was 33.60, and was 16.03 months for patients with preoperative CA72-4 positive levels (p=0.0041). Conclusions The preoperative levels of CEA, CA19-9, CA24-2, CA72-4, and AFP were closely related to TNM grade, gender, distant metastasis and ascites. These makers seem to play important roles in predicting recurrence and metastasis, and in evaluating prognosis.
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Abbas M, Habib M, Naveed M, Karthik K, Dhama K, Shi M, Dingding C. The relevance of gastric cancer biomarkers in prognosis and pre- and post- chemotherapy in clinical practice. Biomed Pharmacother 2017; 95:1082-1090. [PMID: 28922727 DOI: 10.1016/j.biopha.2017.09.032] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2017] [Revised: 09/07/2017] [Accepted: 09/08/2017] [Indexed: 02/07/2023] Open
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Aurello P, Petrucciani N, Antolino L, Giulitti D, D'Angelo F, Ramacciato G. Follow-up after curative resection for gastric cancer: Is it time to tailor it? World J Gastroenterol 2017; 23:3379-3387. [PMID: 28596674 PMCID: PMC5442074 DOI: 10.3748/wjg.v23.i19.3379] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2017] [Revised: 03/22/2017] [Accepted: 04/21/2017] [Indexed: 02/06/2023] Open
Abstract
There is still no consensus on the follow-up frequency and regimen after curative resection for gastric cancer. Moreover, controversy exists regarding the utility of follow-up in improving survival, and the recommendations of experts and societies vary considerably. The main reason to establish surveillance programs is to diagnose tumor recurrence or metachronous cancers early and to thereby provide prompt treatment and prolong survival. In the setting of gastric malignancies, other reasons have been put forth: (1) the detection of adverse effects of a previous surgery, such as malnutrition or digestive sequelae; (2) the collection of data; and (3) the identification of psychological and/or social problems and provision of appropriate support to the patients. No randomized controlled trials on the role of follow-up after curative resection of gastric carcinoma have been published. Herein, the primary retrospective series and systematic reviews on this subject are analyzed and discussed. Furthermore, the guidelines from international and national scientific societies are discussed. Follow-up is recommended by the majority of institutions; however, there is no real evidence that follow-up can improve long-term survival rates. Several studies have demonstrated that it is possible to stratify patients submitted to curative gastrectomy into different classes according to the risk of recurrence. Furthermore, promising studies have identified several molecular markers that are related to the risk of relapse and to prognosis. Based on these premises, a promising strategy will be to tailor follow-up in relation to the patient and tumor characteristics, molecular marker status, and individual risk of recurrence.
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Wang J, Long J, Liu Z, Wu W, Hu C. Label-free and high-throughput biosensing of multiple tumor markers on a single light-addressable photoelectrochemical sensor. Biosens Bioelectron 2017; 91:53-59. [DOI: 10.1016/j.bios.2016.12.029] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Revised: 12/01/2016] [Accepted: 12/12/2016] [Indexed: 11/17/2022]
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Abstract
This article discusses the current National Comprehensive Cancer Network guidelines and other available Western and Eastern guidelines for the surveillance of gastric cancer following surgical resection. It reviews the literature assessing the utility of intensive surveillance strategies for gastric cancer, which fails to show an improvement in survival. The unique issues relating to follow-up of early gastric cancer and after endoscopic resection of early gastric cancer are discussed. This article also reviews the available modalities for follow-up. In addition, it briefly discusses the advancements in treatment of recurrent and metastatic disease and the implications for gastric cancer survival and surveillance strategies.
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Affiliation(s)
- Shachar Laks
- Division of Surgical Oncology, University of North Carolina, 170 Manning Drive, CB #7213, 1150 Physicians Office Building, Chapel Hill, NC 27599-7213, USA
| | - Michael O Meyers
- Division of Surgical Oncology, University of North Carolina, 170 Manning Drive, CB #7213, 1150 Physicians Office Building, Chapel Hill, NC 27599-7213, USA
| | - Hong Jin Kim
- Division of Surgical Oncology, University of North Carolina, 170 Manning Drive, CB #7213, 1150 Physicians Office Building, Chapel Hill, NC 27599-7213, USA.
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Tian SB, Yu JC, Kang WM, Ma ZQ, Ye X, Cao ZJ, Yan C. Combined detection of CEA, CA 19-9, CA 242 and CA 50 in the diagnosis and prognosis of resectable gastric cancer. Asian Pac J Cancer Prev 2017; 15:6295-300. [PMID: 25124614 DOI: 10.7314/apjcp.2014.15.15.6295] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Our aim was to investigate the value of combined detection of serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, CA 242 and CA 50 in diagnosis and assessment of prognosis in consecutive gastric cancer patients. Clinical data including preoperative serum CEA, CA 19-9, CA 242, and CA 50 values and information on clinical pathological factors were collected and analyzed retrospectively. Univariate and multivariate survival analyses were used to explore the relationship between tumor markers and survival. Positive rates of tumor markers CEA, CA 19-9, CA 242 and CA 50 in the diagnosis of gastric cancer were 17.7, 17.1, 20.4 and 13.8%, respectively, and the positive rate for all four markers combined was 36.6%. Patients with elevated preoperative serum concentrations of CEA, CA 19-9, CA 242 and CA 50, had late clinical tumor stage and significantly poorer overall survival. Five-year survival rates in patients with elevated CEA, CA 19-9, CA 242 and CA 50 were 28.1, 25.8, 27.0 and 24.1%, respectively, compared with 55.0, 55.4, 56.4 and 54.5% in patients with these markers at normal levels (p<0.01). In multivariate Cox proportional hazards analyses, an elevated CA 242 level was determined to be an independent prognostic marker in gastric cancer patients. Combined detection of four tumor markers increased the positive rate for gastric cancer diagnosis. CA 242 showed higher diagnostic value and CA 50 showed lower diagnostic value. In resectable gastric carcinoma, preoperative CA 242 level was associated with disease stage, and was found to be a significant independent prognostic marker in gastric cancer patients.
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Affiliation(s)
- Shu-Bo Tian
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China E-mail :
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Gong W, Shou D, Gong P. Extremely high expression of serum alpha-fetoprotein level of gastric adenocarcinoma: a rare case with an unexpected well-prognosis. SPRINGERPLUS 2016; 5:2056. [PMID: 27995033 PMCID: PMC5133213 DOI: 10.1186/s40064-016-3719-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/12/2016] [Accepted: 11/21/2016] [Indexed: 12/04/2022]
Abstract
Introduction Alpha-fetoprotein (AFP)-producing gastric cancer is a relatively rare form of stomach malignancy. Patients with higher serum AFP level (>300 ng/mL) will have a poorer prognosis. Case description In this study, we present a case of 77-year-old woman with an extremely high expression of serum AFP level (>10,000 ng/mL) of gastric cancer. Histological examination revealed gastric adenocarcinoma (Bormann III gastric tumor) invading into the serosal layer and vessel. After receiving a successful total gastrectomy with D2 dissection, this patient underwent chemotherapy with SOX [oxaliplatin (130 mg/m2/day) iv. at day 1 + S-1 (80 mg/m2/day) from day 1–day 14]. The patient remains alive without disease for 29 months after surgery. Serum AFP level decreased to normal range. Discussion and Evaluation We have evaluated the level of AFP, and discussed the reason for the good prognosis for this patient. Conclusions The good prognosis may be related with her early stage (N0 and without liver metastasis) and radical surgery.
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Affiliation(s)
- Weihua Gong
- Department of Surgery and Medicine, Second Affiliated Hospital of School of Medicine, Zhejiang University, Jiefang Road #88, Hangzhou City, 310009 Zhejiang Province People's Republic of China
| | - Dawei Shou
- Department of Surgery and Medicine, Second Affiliated Hospital of School of Medicine, Zhejiang University, Jiefang Road #88, Hangzhou City, 310009 Zhejiang Province People's Republic of China
| | - Ping Gong
- Department of Oncology, First Affiliated Hospital of Shihezi University School of Medicine, Shihezi City, People's Republic of China
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Wang W, Chen XL, Zhao SY, Xu YH, Zhang WH, Liu K, Chen XZ, Yang K, Zhang B, Chen ZX, Chen JP, Zhou ZG, Hu JK. Prognostic significance of preoperative serum CA125, CA19-9 and CEA in gastric carcinoma. Oncotarget 2016; 7:35423-35436. [PMID: 27097114 PMCID: PMC5085240 DOI: 10.18632/oncotarget.8770] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2015] [Accepted: 04/05/2016] [Indexed: 02/05/2023] Open
Abstract
The prognostic significance of preoperative serum CA125, CA19-9 and CEA in gastric carcinoma (GC) has been widely reported and is still under debate. Here, we evaluated the prognostic significance of preoperative serum CA125, CA19-9 and CEA in patients with GC. 1692 patients with GC who underwent gastrectomy were divided into the training (from January 2005 to December 2011, n = 1024) and the validation (from January 2012 to December 2013, n = 668) cohorts. Positive groups of CA125 (> 13.72 U/ml), CA19-9 (> 23.36 U/ml) and CEA (> 4.28 ng/ml) were significantly associated with more advanced clinicopathological traits and worse outcomes than that of negative groups (all P < 0.01). In Cox regression analysis, tumor size (P < 0.001, P = 0.005), pTNM stage (P < 0.001, P < 0.001) and CA125 (P = 0.026, P = 0.005) were independent prognostic factors both in two cohorts. Nomograms of these two cohorts based on the number of positive serum tumor markers (NPTM) were more accurate in prognostic prediction than TNM stage alone. Our findings suggested that elevated preoperative serum CA125, CA19-9 and CEA were associated with more advanced clinicopathological traits and less favorable outcomes. In addition, CA125 as an independent prognostic factor should be further investigated. Nomogram based on NPTM could accurately predict the prognosis of GC patients.
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Affiliation(s)
- Wei Wang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Xiao-Long Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Shen-Yu Zhao
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Yu-Hui Xu
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Wei-Han Zhang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Kai Liu
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Xin-Zu Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Kun Yang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Bo Zhang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Zhi-Xin Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Jia-Ping Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Zong-Guang Zhou
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Digestive Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Jian-Kun Hu
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
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Zhou YC, Zhao HJ, Shen LZ. Preoperative serum CEA and CA19-9 in gastric cancer--a single tertiary hospital study of 1,075 cases. Asian Pac J Cancer Prev 2016; 16:2685-91. [PMID: 25854347 DOI: 10.7314/apjcp.2015.16.7.2685] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
To evaluate the clinical impact of preoperative serum CEA and CA19-9 on resectable gastric cancer (GC), a total of 1,075 consecutive cases with gastric adenocarcinoma were obtained retrospectively from January 2012 and December 2013 in a single tertiary hospital, and the relationships between serum CEA, CA19-9 and clinicopathologic features were investigated. Positive preoperative serum rates of CEA and CA19-9 were 22.4% and 12.3% respectively, levels significantly correlating with each other and depth of invasion, lymph node involvement, pTNM and stage. The CEA level also presented a remarkable association with lymphovascular invasion. Both CEA and CA19-9 positivity significantly and positively correlated with depth of invasion, nodal involvement, pTNM stage, lymphovascular invasion, tumor size and tumor location. Stratified analyses according to gender or tumor location showed preoperative CEA or CA19-9 had different associations with clinicopathologic features in different gender subgroups or location subgroups. Preoperative serum CA19-9 positivity may be more meaningful for tumor size rather than CEA. In conclusion, preoperative serum CEA and CA19-9 correlate with disease progression of GC, and may have applications in aiding more accurate estimation of tumor stage, decision of treatment choice and prognosis evaluation.
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Affiliation(s)
- Yang-Chun Zhou
- Division of Gastrointestinal Surgery, Department of General Surgery, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China E-mail :
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High level of serum AFP is an independent negative prognostic factor in gastric cancer. Int J Biol Markers 2015; 30:e387-93. [PMID: 26349668 DOI: 10.5301/jbm.5000167] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/17/2015] [Indexed: 01/13/2023]
Abstract
BACKGROUND Gastric cancer with a high level of serum alpha fetoprotein (AFP) is uncommon and has unique clinicopathological features and a poorer prognosis. The aim of this research was to elucidate the clinicopathological and prognostic features of gastric cancer with a high level of AFP. METHODS The sera from 1,286 patients with gastric cancer treated at Qilu Hospital of Shandong University from January 2004 to December 2008 were analyzed preoperatively for AFP, CEA and CA19-9 levels after excluding active or chronic hepatitis, liver cirrhosis and hepatocellular carcinoma as well as preoperative distant metastasis. Patients were divided into 2 groups: 86 serum AFP-positive patients and 1,200 serum AFP-negative patients according to a cutoff of 20 ng/mL. The clinicopathological features and prognostic factors were compared between the groups. RESULTS A higher incidence of serosal invasion, lymph node metastasis and liver metastasis and poorer prognosis was observed in the AFP-positive group compared with the AFP-negative group (all p<0.05). Serum AFP showed the highest specificity (93.66%) and diagnostic accuracy (92.38%) for predicting liver metastasis among the 3 tumor markers examined. Multivariate survival analysis revealed that AFP positivity was an independent prognostic factor in all 1,286 gastric cancer patients. The prognosis of AFP-positive gastric cancer was poorer than that of AFP-negative gastric cancer (p<0.05). CONCLUSIONS A high level of serum AFP is an independent prognostic factor in gastric cancer and can be used for evaluating the prognosis of gastric cancers whether in the presence or absence of liver metastasis.
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Jing JX, Wang Y, Xu XQ, Sun T, Tian BG, Du LL, Zhao XW, Han CZ. Tumor markers for diagnosis, monitoring of recurrence and prognosis in patients with upper gastrointestinal tract cancer. Asian Pac J Cancer Prev 2015; 15:10267-72. [PMID: 25556459 DOI: 10.7314/apjcp.2014.15.23.10267] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
To evaluate the value of combined detection of serum CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS for the clinical diagnosis of upper gastrointestinal tract (GIT) cancer and to analyze the efficacy of these tumor markers (TMs) in evaluating curative effects and prognosis. A total of 573 patients with upper GIT cancer between January 2004 and December 2007 were enrolled in this study. Serum levels of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were examined preoperatively and every 3 months postoperatively by ELISA. The sensitivity of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were 26.8%, 36.2%, 42.9%, 2.84%, 25.4%, 34.6%, 34.2% and 30.9%, respectively. The combined detection of CEA+CA199+CA242+CA724 had higher sensitivity and specificity in gastric cancer (GC) and cardiac cancer, while CEA+CA199+CA242+SCC was the best combination of diagnosis for esophageal cancer (EC). Elevation of preoperative CEA, CA19-9 and CA24-2, SCC and CA72-4 was significantly associated with pathological types (p<0.05) and TNM staging (p<0.05). Correlation analysis showed that CA24-2 was significantly correlated with CA19-9 (r=0.810, p<0.001). The levels of CEA, CA19-9, CA24-2, CA72-4 and SCC decreased obviously 3 months after operations. When metastasis and recurrence occurred, the levels of TMs significantly increased. On multivariate analysis, high preoperative CA72-4, CA24-2 and SCC served as prognostic factors for cardiac carcinoma, GC and EC, respectively. combined detection of CEA+CA199+CA242+SCC proved to be the most economic and practical strategy in diagnosis of EC; CEA+CA199+CA242+CA724 proved to be a better evaluation indicator for cardiac cancer and GC. CEA and CA19-9, CA24-2, CA72-4 and SCC, examined postoperatively during follow-up, were useful to find early tumor recurrence and metastasis, and evaluate prognosis. AFP, TPA and TPS have no significant value in diagnosis of patients with upper GIT cancer.
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Affiliation(s)
- Jie-Xian Jing
- Department of Etiology and Tumor Markers Laboratory, Shanxi Cancer Hospital, Shanxi Province, China E-mail :
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Lee EC, Yang JY, Lee KG, Oh SY, Suh YS, Kong SH, Yang HK, Lee HJ. The value of postoperative serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels for the early detection of gastric cancer recurrence after curative resection. J Gastric Cancer 2014; 14:221-8. [PMID: 25580353 PMCID: PMC4286900 DOI: 10.5230/jgc.2014.14.4.221] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2014] [Revised: 10/04/2014] [Accepted: 10/05/2014] [Indexed: 12/15/2022] Open
Abstract
PURPOSE This study aimed to evaluate the value of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels to detect gastric cancer recurrence. MATERIALS AND METHODS We retrospectively reviewed 154 patients who developed recurrence within 2 years after curative gastric cancer surgery and analyzed the relationship between postoperative CEA and CA19-9 levels and recurrence. We readjusted the cut-off values to improve the detection of recurrence. Subgroup analysis according to clinicopathologic variables was performed to further investigate the relationship between recurrence and CEA and CA19-9 levels. RESULTS The sensitivity and specificity for elevated CEA levels to detect recurrence were 40.6% and 89.5%, respectively, and those for CA19-9 were 34.2% and 93.6%, respectively. The sensitivity and specificity for elevation of either tumor marker were 54.3% and 84.0%, respectively; those for elevation of both tumor markers were 19.2% and 98.4%, respectively. By readjusting the cut-off values from 5.0 ng/ml to 5.2 ng/ml for CEA and from 37.00 U/ml to 30.0 U/ml for CA19-9, the sensitivity was increased from 34.2% to 40.2% for CA19-9, while there was no increase in sensitivity for CEA. In subgroup analysis, the sensitivity of CEA was higher in patients with elevated preoperative CEA levels than in patients with normal preoperative CEA levels (86.7% versus 33.7%; P<0.001). Furthermore, the sensitivity of CA19-9 was higher in patients with elevated preoperative CA19-9 levels than in patients with normal preoperative CA19-9 levels (82.61% versus 26.83%; P<0.001). CONCLUSIONS CEA and/or CA19-9 measurement with the readjusted cut-off values allows for more effective detection of gastric cancer recurrence.
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Affiliation(s)
- Eung-Chang Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jun-Young Yang
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung-Goo Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Seung-Young Oh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Yun-Suhk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Seong-Ho Kong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Han-Kwang Yang
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea. ; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hyuk-Joon Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea. ; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Galli C, Basso D, Plebani M. CA 19-9: handle with care. Clin Chem Lab Med 2014; 51:1369-83. [PMID: 23370912 DOI: 10.1515/cclm-2012-0744] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2012] [Accepted: 12/13/2012] [Indexed: 12/11/2022]
Abstract
Since its inception in the mid-1980s of the 20th century testing for carbohydrate antigen 19-9 (CA 19-9) has raised expectation for an earlier diagnosis and accurate monitoring of several malignant diseases. After almost 30 years, the available evidences have confirmed the appropriateness and usefulness of determining CA 19-9 levels as a prognostic indicator and as a reliable tool for monitoring pancreatic and gastrointestinal cancer, but concerns have been raised about its applications in screening, which is actually not recommended, and in the diagnosis of malignancies, due to several interferences that limit the specificity and to the insufficient sensitivity of this marker. In this paper we aimed to review the basic concepts of CA 19-9 testing and its current applications, with a major focus on the most recent evidences dealing with assay interference, methods comparison and monitoring of malignant diseases. The prognostic value and monitoring recommendations for pancreatic, gastric and colorectal cancers are described in depth.
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Affiliation(s)
- Claudio Galli
- Scientific Affairs, Abbott Diagnostics Division, Rome, Italy
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Shimada H, Noie T, Ohashi M, Oba K, Takahashi Y. Clinical significance of serum tumor markers for gastric cancer: a systematic review of literature by the Task Force of the Japanese Gastric Cancer Association. Gastric Cancer 2014; 17:26-33. [PMID: 23572188 DOI: 10.1007/s10120-013-0259-5] [Citation(s) in RCA: 352] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2012] [Accepted: 03/24/2013] [Indexed: 02/06/2023]
Abstract
The aim of this review was to evaluate the clinical significance of serum tumor markers, particularly CEA, CA19-9, and CA72-4, in patients with gastric cancer. A systematic literature search was performed using PubMed/MEDLINE with the keywords "gastric cancer" and "tumor marker," to select 4,925 relevant reports published before the end of November 2012. A total of 187 publications contained data for CEA and CA19-9, and 19 publications contained data related to all three tumor markers. The positive rates were 21.1 % for CEA, 27.8 % for CA19-9, and 30.0 % for CA72-4. These three markers were significantly associated with tumor stage and patient survival. Serum markers are not useful for early cancer, but they are useful for detecting recurrence and distant metastasis, predicting patient survival, and monitoring after surgery. Tumor marker monitoring may be useful for patients after surgery because the positive conversion of tumor markers usually occurs 2-3 months before imaging abnormalities. Among other tumor markers, alpha-fetoprotein (AFP) is useful for detecting and predicting liver metastases. Moreover, CA125 and sialyl Tn antigens (STN) are useful for detecting peritoneal metastases. Although no prospective trial has yet been completed to evaluate the clinical significance of these serum markers, this literature survey suggests that combinations of CEA, CA19-9, and CA72-4 are the most effective ways for staging before surgery or chemotherapy. In particular, monitoring tumor markers that were elevated before surgery or chemotherapy could be useful for detection of recurrence or evaluation of the response.
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Affiliation(s)
- Hideaki Shimada
- Department of Surgery, School of Medicine, Toho University, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan,
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Lee JC, Lee SY, Kim CY, Yang DH. Clinical utility of tumor marker cutoff ratio and a combination scoring system of preoperative carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 72-4 levels in gastric cancer. JOURNAL OF THE KOREAN SURGICAL SOCIETY 2013; 85:283-9. [PMID: 24368986 PMCID: PMC3868680 DOI: 10.4174/jkss.2013.85.6.283] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2013] [Revised: 10/07/2013] [Accepted: 10/08/2013] [Indexed: 12/17/2022]
Abstract
Purpose The present study is to investigate the clinical utility of tumor marker cutoff ratio (TMR) and develop a TMR combination scoring system based on preoperative tumor marker (TM) levels to prognosis prediction in gastric cancer. Methods We include 1,142 patients for whom two or more TMs were measured and who underwent radical gastrectomy between 1990 and 2003. Results Five-year risk of recurrence (5 YRR) for carcinoembryonic antigen (CEA) TMRs were 18.3%, 29.8%, 61.4% for TMR < 1.0, 1.0 ≤ TMR < 2.0, TMR ≥ 2.0 respectively. 5 YRR for carbohydrate antigen 19-9 (CA 19-9) TMR were 19.7%, 35.6%, 58.4% for TMR < 1.0, 1.0 ≤ TMR < 3.0, TMR ≥ 3.0, respectively. 5 YRR for carbohydrate antigen 72-4 (CA 72-4) TMR were 15.2% and 33.6% for TMR < 1.0 and TMR ≥ 1.0, respectively. We defined high TMR (TMR ≥ 2.0 for CEA, TMR ≥ 3.0 for CA19-9), low TMR (1.0 ≤ TMR < 2 for CEA, 1.0 ≤ TMR < 3.0 for CA 19-9 and 1.0 ≤ TMR for CA72-4) and negative TMR (TMR < 1.0 for all TMs). A TMR combination scoring system was devised with negative scored as zero points, low as 1 and high as 2 for each TMR. TMR scores were divided into four categories (score 0, 1, 2, 3 and above) based on the calculated TMR score and 5 YRR were found to be 12.8%, 23.9%, 45.5%, and 68.3%, respectively (P < 0.05). Multivariate analysis showed that our scoring system was a significant independent prognostic factor. Conclusion Preoperative TMRs such as CEA, CA 19-9, and CA 72-4 show a correlation with prognosis and the TMR combination scoring system could be a useful tool for the prediction of prognosis in gastric cancer.
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Affiliation(s)
- Jong-Chan Lee
- Department of Surgery, Chonbuk National University Medical School, Jeonju, Korea
| | - Se Youl Lee
- Department of Surgery, Chonbuk National University Medical School, Jeonju, Korea
| | - Chan Young Kim
- Department of Surgery, Chonbuk National University Medical School, Jeonju, Korea
| | - Doo Hyun Yang
- Department of Surgery, Chonbuk National University Medical School, Jeonju, Korea
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Choi AR, Park JC, Kim JH, Shin SK, Lee SK, Lee YC, Chung JB. High level of preoperative carbohydrate antigen 19-9 is a poor survival predictor in gastric cancer. World J Gastroenterol 2013; 19:5302-5308. [PMID: 23983433 PMCID: PMC3752564 DOI: 10.3748/wjg.v19.i32.5302] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2013] [Revised: 07/10/2013] [Accepted: 07/19/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the clinical significance and the prognostic value of preoperative serum carbohydrate antigen 19-9 (CA 19-9) level in gastric cancer.
METHODS: Between January 2005 and December 2006, 1960 patients underwent surgery for histologically confirmed gastric cancer. Of these, 163 patients had elevated serum levels of CA 19-9 preoperatively, and 1628 patients had normal serum levels of CA 19-9 preoperatively. For this study, 325 patients were selected from the group of 1628 patients by age, sex, and cancer stage to serve as controls. Statistically significant differences in survival rates were calculated using the log-rank test. A P value less than 0.05 was considered statistically significant and was determined using SAS software.
RESULTS: The baseline characteristics showed some differences between the two groups with regard to histology. Overall survival (OS) in the elevated and non-elevated group was 37.90 and 68.67 mo, respectively (P < 0.001). N stage (P = 0.001) was a significant predictor of disease-free survival by multivariate analysis. Also, N stage (P < 0.001), and the presence of peritoneal metastasis (P < 0.001) remained independent factors in predicting OS by multivariate analysis. Additionally, preoperative serum CA 19-9 levels were significantly associated with OS in univariate (P = 0.009) and multivariate (P = 0.021) analyses.
CONCLUSION: Serum CA 19-9 can be considered an independent prognostic factor in predicting OS in patients anticipating surgery for gastric cancer.
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Abstract
There is currently no consensus on the best strategy for the follow-up of patients who have undergone surgical treatment with curative intent for gastric cancer. The wide variation in recommendations for surveillance among international experts and hospital schedules clearly reflects a lack of an established body of evidence on this subject. Consequently, most of the international guidelines aimed at early detection of disease recurrence gloss over details concerning the mode, duration, and intensity of surveillance since they cannot be based on an acceptable grade of recommendation. Very few report anything other than the detection of recurrences or death as the primary endpoints, and, given the poor survival of patients with recurrent gastric cancer, the prognostic effect of early detection seems doubtful. In recent years, an increasing focus on evidence-based medicine, which has coincided with a growing concern about costs and efficiency in medicine, has caused a reevaluation of most surveillance practices. In this paper, we review and discuss the current body of evidence and follow-up practices after curative resection of gastric cancer.
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Affiliation(s)
- Domenico D'Ugo
- Department of Surgery, A. Gemelli Hospital, Università Cattolica del Sacro Cuore, IT-00167 Rome, Italy.
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Passerini R, Cassatella MC, Boveri S, Salvatici M, Radice D, Zorzino L, Galli C, Sandri MT. The pitfalls of CA19-9: routine testing and comparison of two automated immunoassays in a reference oncology center. Am J Clin Pathol 2012; 138:281-7. [PMID: 22904141 DOI: 10.1309/ajcpopnpllcyr07h] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
We evaluated CA19-9 as a marker of various malignancies and compared the results of 2 commercial immunoassays. The Abbott ARCHITECT i2000 and Roche cobas 410 immunoassays were used on 500 consecutive samples to evaluate the frequency of positive results by cancer type and the correlation between assays. The patients were tested before or after surgery and/or during chemotherapy. The rate of results exceeding conventional thresholds was 92.3% in pancreatic cancer, 36.8% in gastric cancer, and ranged from 3.0% to 35.9% in other tumors. Agreement (90.6%) and correlation (R(2) = 0.865) between the 2 assays were good and the frequency of highly discordant results was low (6/500). In some cases, interference by heterophilic antibodies was demonstrated. The 2 methods were comparable in diagnostic accuracy and had good correlation but are not interchangeable. Patients should always be monitored for CA19-9 with the same method and it should be indicated in the report.
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Affiliation(s)
- Rita Passerini
- Division of Laboratory Medicine, European Institute of Oncology, Milan, Italy
| | - Maria C. Cassatella
- Division of Laboratory Medicine, European Institute of Oncology, Milan, Italy
| | - Sara Boveri
- Preventive Gynecology Unit, European Institute of Oncology, Milan, Italy
| | - Michela Salvatici
- Division of Laboratory Medicine, European Institute of Oncology, Milan, Italy
| | - Davide Radice
- Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy
| | - Laura Zorzino
- Division of Laboratory Medicine, European Institute of Oncology, Milan, Italy
| | | | - Maria T. Sandri
- Division of Laboratory Medicine, European Institute of Oncology, Milan, Italy
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Kim M, Kim HJ, Choi BY, Kim JH, Song KS, Noh SM, Kim JC, Han DS, Kim SY, Kim YS. Identification of potential serum biomarkers for gastric cancer by a novel computational method, multiple normal tissues corrected differential analysis. Clin Chim Acta 2012; 413:428-33. [DOI: 10.1016/j.cca.2011.10.026] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2011] [Revised: 10/04/2011] [Accepted: 10/19/2011] [Indexed: 01/05/2023]
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Molina R, Bosch X, Auge JM, Filella X, Escudero JM, Molina V, Solé M, López-Soto A. Utility of serum tumor markers as an aid in the differential diagnosis of patients with clinical suspicion of cancer and in patients with cancer of unknown primary site. Tumour Biol 2011; 33:463-74. [PMID: 22161237 DOI: 10.1007/s13277-011-0275-1] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2011] [Accepted: 11/10/2011] [Indexed: 01/21/2023] Open
Abstract
Cancer may be diagnosed in advanced stages, when the patient has already developed metastasis, with symptoms that can be also observed in benign diseases. The objective of this study was to evaluate tumor marker sensitivity and specificity in the differential diagnosis of patients with suspected signs of cancer. We studied 2.711 consecutive patients admitted to the Internal Medicine Department of our hospital with suspected cancer; 1.240 patients had non-malignant processes and 1.471 had malignant disease. Determinations were considered positive for suspected malignancy when serum levels were carcinoembryonic antigen >15 ng/ml (>20 in patients with renal failure or liver disease), alpha fetoprotein >40 ng/ml (>80 ng/ml in patients with liver diseases), carbohydrate antigen (CA) 19.9 > 200 U/ml (>500 U/ml in patients with liver diseases or gamma glutamyl transpeptidase (GGT) <150 UI/L or effusions; >1.000 U/ml in patients with jaundice or GGT > 150 UI/L), neuron-specific enolase >45 ng/ml (renal failure >50 ng/ml; samples with hemolysis were excluded), prostate-specific antigen > 30 ng/ml (excluding acute prostatitis), tumor-associated glycoprotein-72 >80 U/ml, cytokeratin 19 fragment 21-1 > 7.5 ng/ml (>19 ng/ml in patients with renal failure; >11 ng/ml in patients with liver cirrhosis or jaundice), >3.5 ng/ml for squamous cell carcinoma (excluding patients with renal failure or skin disorders), CA 15.3 >100 U/ml, and CA 125 >350 U/ml (>600 U/ml in patients with pleural effusion and >900 U/ml in those with ascites). There was a specificity of 97.6% in patients without malignancy, 67.4% of sensitivity in patients with malignancy, and 75.4% of sensitivity in the 1,280 patients with epithelial tumors (53.7% in patients with locally advanced tumors and 79.4% in patients with metastases). Sensitivity was 81.4% in patients with cancer of unknown primary site. Tumor markers were useful in the differential diagnosis between epithelial and non-epithelial tumors, brain masses (metastases vs. primary tumors), and between benign or malignant origin of different clinical situations such as wasting syndrome, effusions, liver or bone lesions, and effusions with a positive predictive value higher than 95%. Tumor markers are useful as an aid in the evaluation of the risk of cancer of these patients with suspected cancer and may be useful to reduce the hospitalization time, morbidity, and the number of diagnostic tests required for diagnosis.
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Affiliation(s)
- Rafael Molina
- Laboratory of Clinical Biochemistry (Unit for Cancer Research), Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Villarroel 170, Barcelona, 08036, Spain.
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Woo Y, Hyung WJ, Obama K, Kim HI, Pak KH, Son T, Noh SH. Elevated high-sensitivity C-reactive protein, a marker of advanced stage gastric cancer and postgastrectomy disease recurrence. J Surg Oncol 2011; 105:405-9. [PMID: 22025360 DOI: 10.1002/jso.22129] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2011] [Accepted: 09/30/2011] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND OBJECTIVES Gastric cancer recurrence after curative surgery remains high. Although no preoperative marker of gastric cancer progression after radical gastrectomy exists, recent studies suggest that C-reactive protein (CRP) is associated with cancer progression. Our study evaluated the significance of preoperative high-sensitivity CRP (hs-CRP) levels as a marker of disease progression after radical gastrectomy. METHODS The preoperative hs-CRP levels of 1,221 gastric cancer patients who underwent radical gastrectomies were analyzed for clinicopathologic significance. Patients with previous gastric cancer treatment, another primary cancer, active infection, or postoperative mortality were excluded. RESULTS hs-CRP levels were significantly associated with increased tumor depth (P = 0.028), nodal status (P = 0.012), and stage (P = 0.045). Seventeen percent of patients had elevated hs-CRP levels at the cutoff value of >3.00 mg/L, whereas 6.6% and 6.1% of patients had CEA and CA-19-9 levels about the cutoffs of ≥5.00 ng/ml and ≥35.0 U/L, respectively. Hs-CRP levels >3.00 mg/L were an independent risk factor for recurrence-free survival along with stage. CONCLUSION Elevated preoperative hs-CRP levels in gastric cancer patients are clinically significant indicators of advanced stage and postoperative disease recurrence.
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Affiliation(s)
- Yanghee Woo
- Department of Surgery, Yonsei University College of Medicine, Seodaemungu, Seoul, Korea
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Li Z, Wang Y, He J, Ma J, Zhao L, Chen H, Li N, Zhou J, He E, Skog S. Serological thymidine kinase 1 is a prognostic factor in oesophageal, cardial and lung carcinomas. Eur J Cancer Prev 2010; 19:313-318. [PMID: 20479645 DOI: 10.1097/cej.0b013e32833ad320] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
In this study we examine the use of the concentration of thymidine kinase 1 in serum (STK1) as a prognostic factor in routine clinical settings. For this purpose we used sera from patients with oesophageal (n=101) and cardial (n=39) carcinomas and nonsmall-cell lung carcinoma (NSCLC) (n=157). Sera from healthy individuals (n=95) were used as controls. STK1 was analysed by a chemiluminiscence dot blot assay. The mean STK1 concentrations and the STK1 positive rates of the patients with oesophageal and cardial carcinomas and with NSCLC were significantly higher as compared with healthy controls (P=0.01). The mean STK1 value of oesophageal carcinoma patients correlated with T-values (P=0.021) and with stage (P<0.005), but not with grade. The mean STK1 value of cardial carcinoma patients did not correlate with grade. No data on stage and T-values were available for these patients, due to advanced disease. The mean STK1 value of NSCLC patients with squamous cell carcinoma was significantly higher as compared with adenocarcinoma type (P=0.024). The mean STK1 value of the NSCLC patients correlated with clinical grade (P=0.006), T-values (P=0.001), stage (P=0.035) and to size of the tumour (P=0.030). The mean STK1 value and the number of STK1 positive patients were also higher in recurrent NSCLC patients. There was a tendency that stage I-II NSCLC patients with an STK1 level above 2 pmol/l showed a higher frequency of recurrence/death than patients below 1 pmol/l. Our results show that STK1 is a useful marker for prognosis in patients with oesophageal, cardial and lung carcinomas.
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Affiliation(s)
- Zhishan Li
- Department of Thoracic Surgery Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Science, Beijing, PR China
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Ni XF, Wu CP, Jiang JT. Serum VEGFR-3 and survival of advanced gastric cancer patients treated with FOLFOX. World J Gastroenterol 2010; 16:2163-9. [PMID: 20440858 PMCID: PMC2864843 DOI: 10.3748/wjg.v16.i17.2163] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore if vascular endothelial growth factor receptor-3 (VEGFR-3) and carcinoembryonic antigen (CEA) can predict overall survival in advanced gastric cancer.
METHODS: VEGFR-3 level was assessed by enzyme-linked immunosorbent assay, and CEA was assessed by chemiluminescence immunoassay in the sera of 81 advanced gastric cancer patients before treatment with oxaliplatin plus 5-fluorouracil and folinic acid.
RESULTS: Median survival time in patients with a low serum VEGFR-3 level was significantly longer than in those with a higher VEGFR-3 level (15.4 mo vs 7.7 mo, P < 0.001). Patients with a low CEA level had a longer survival than those with a higher CEA level (15.8 mo vs 8.6 mo, P < 0.001). Thirty-nine patients with low VEGFR-3 and low CEA levels had a median survival of 19.7 mo (P = 0.0006). The hazard ratio for patients with a high VEGFR-3 level was 2.443 (P = 0.002).
CONCLUSION: High serum VEGFR-3 level is correlated significantly with poor survival. In patients with a high serum level of VEGFR-3, alternative chemotherapy regimens should be considered.
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Jung M, Jeung HC, Lee SS, Park JY, Hong S, Lee SH, Noh SH, Chung HC, Rha SY. The clinical significance of ascitic fluid CEA in advanced gastric cancer with ascites. J Cancer Res Clin Oncol 2010; 136:517-26. [PMID: 19774395 DOI: 10.1007/s00432-009-0684-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2009] [Accepted: 09/14/2009] [Indexed: 01/13/2023]
Abstract
BACKGROUND This study was carried out to evaluate the clinical significance of ascitic fluid carcinoembryonic antigen (CEA) in advanced gastric cancer patients with ascites. PATIENTS AND METHODS From November 2001 to February 2008, 119 gastric cancer patients with concurrent ascites who were clinically diagnosed with carcinomatosis, were retrospectively reviewed with regard to ascitic fluid cytology and clinicopathological parameters. Serum CEA (sCEA) and ascitic fluid CEA (aCEA) were measured using a chemiluminescent enzyme immunoassay. RESULTS The patients' median age was 50 years (range 23-80 years). The median value of aCEA was significantly higher than sCEA [130.5 ng/ml (range 0.2-12.211 ng/ml) vs. 2.1 ng/ml (range 0.02-8.152 ng/ml), p < 0.001]. Sixty-five patients (54.6%) had positive ascitic fluid cytology. The median overall survival of all patients was 3.0 months (95% CI 2.0-4.0 months). The patients with low aCEA (<5 ng/ml) had a significantly longer overall survival compared to patients with high aCEA (>or=5 ng/ml) (7.4 months vs. 2.3 months, p = 0.003). However, we found no difference in overall survival according to ascitic fluid cytology (median, 3.0 months vs. 2.5 months, p = 0.530). Multivariate analysis also demonstrated that aCEA levels of more than 5 ng/ml were associated with poor prognosis (HR = 2.88; 95% CI 1.45-5.74; p = 0.003), while sCEA levels were not associated with poor prognosis (HR = 1.15; 95% CI 0.67-2.03; p = 0.622). CONCLUSION These results suggest that aCEA levels can be used as a prognostic marker for advanced gastric cancer patients with ascites.
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Affiliation(s)
- Minkyu Jung
- Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul, 120-752, Korea
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Strategies for treating liver metastasis from gastric cancer. Surg Today 2010; 40:287-94. [PMID: 20339981 DOI: 10.1007/s00595-009-4152-0] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2009] [Accepted: 06/16/2009] [Indexed: 12/16/2022]
Abstract
The prognosis of patients with liver metastasis from gastric cancer is dismal. This article reviews the characteristics of gastric cancer metastasizing to the liver, and multimodality of treatments. Differentiated adenocarcinoma, poorly differentiated adenocarcinoma with a medullary growth pattern, and special types, including endocrine carcinoma and hepatoid carcinoma, are likely to metastasize to the liver. The overexpression of growth factors or adhesion molecules is clinically significant for liver metastasis. Surgery for liver metastases arising from gastric adenocarcinoma is reasonable if a complete resection seems feasible after careful preoperative staging. A hepatic resection should always be considered as an option for gastric cancer patients with hepatic metastases. Newer generation cytotoxic agents such as S-1, irinotecan, and taxanes show promising activity for patients with metastases. Adjuvant chemotherapy or molecular targeted therapy will provide significant benefits to patients in the future.
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Sohn YJ, Jang JS, Choi SR, Kwon HC, Jung GJ, Kim MC, Jeong JS. Early detection of recurrence after endoscopic treatment for early gastric cancer. Scand J Gastroenterol 2010; 44:1109-14. [PMID: 19593687 DOI: 10.1080/00365520903121701] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Although there have been many reports regarding clinical outcomes of endoscopic treatment for early gastric cancer (EGC), little is known about detection of recurrence after endoscopic submucosal dissection (ESD). This study aims to clarify the clinical value of serological marker or imaging tools, including conventional CT and PET-CT scans, in detecting recurrent gastric cancer after ESD in Korea. MATERIAL AND METHODS From July 2004 to March 2008, 212 patients who had received ESD for EGC were enrolled in the study. For preoperative staging, conventional CT and PET-CT scans were performed in 141 patients, and for detection of recurrence of cancer, conventional CT, PET-CT scans and tumour marker; CEA, CA19-9, AFP were checked in 165 patients. RESULTS The local recurrence rate was 4.7% (10/212) during the study period. At 9 months after endoscopic treatment, 3 cases recurred. Four showed recurrence at 12 months, 2 at 18 months and 1 at 24 months. The positive rate was 7.1% (10/141) in conventional CT and 0% (0/24) in PET-CT scans for preoperative staging. Conventional CT and PET-CT scans could not detect local recurrence of cancer during the follow-up period. Tumour markers did not show any significant correlation with recurrence of cancer. CONCLUSIONS The study suggests that conventional CT, PET-CT scans and tumour marker have no role in the primary surveillance of early gastric cancer and/or in detecting recurrence after endoscopic treatment. For early diagnosis of recurrence after endoscopic treatment, a biopsy specimen from the endoscopic examination has to be obtained at regular intervals.
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Affiliation(s)
- You Jung Sohn
- Department of Internal Medicine, Dong-A Medical Center, University of College of Medicine, Busan, Korea
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Zhao ZS, Chu YQ, Ye ZY, Wang YY, Tao HQ. Overexpression of matrix metalloproteinase 11 in human gastric carcinoma and its clinicopathologic significance. Hum Pathol 2010; 41:686-96. [PMID: 20060156 DOI: 10.1016/j.humpath.2009.10.010] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2009] [Revised: 10/09/2009] [Accepted: 10/15/2009] [Indexed: 01/26/2023]
Abstract
Matrix metalloproteinase 11 (stromelysin-3) has recently been reported to play a key role in human tumor progression and poor clinical outcome. The aim of this study was to investigate the significance of matrix metalloproteinase 11 expression in gastric cancer. Using real-time quantitative reverse-transcription polymerase chain reaction analysis and immunohistochemistry, we studied matrix metalloproteinase 11 expression levels in non-malignant gastric tissues and in gastric cancer tissues. The association between matrix metalloproteinase 11 expression levels and tumor stage and grade, as well as metastatic potential, was analyzed. Our results show that matrix metalloproteinase 11 expression was significantly higher in gastric cancer specimens compared with nonmalignant tissues at both transcriptional and protein levels, indicating its positive role in the development of gastric cancer. In addition, increased matrix metalloproteinase 11 expression levels were associated with advanced-stage and high-grade tumors, suggesting its involvement in the progression of gastric cancer. More importantly, increased matrix metalloproteinase 11 expression in gastric cancer specimens was correlated with increased expression of IGF-1, a molecule known to stimulate the proliferation, enhanced survival, and migration of cancer cells. Our results demonstrate that matrix metalloproteinase 11 is a novel factor in the development and progression of gastric cancer and suggest that matrix metalloproteinase 11 is a marker for advanced gastric cancer.
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Affiliation(s)
- Zhong-Sheng Zhao
- Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou 310014, China.
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Ikeguchi M, Hatada T, Yamamoto M, Miyake T, Matsunaga T, Fukumoto Y, Yamada Y, Fukuda K, Saito H, Tatebe S. Serum interleukin-6 and -10 levels in patients with gastric cancer. Gastric Cancer 2009; 12:95-100. [PMID: 19562463 DOI: 10.1007/s10120-009-0509-8] [Citation(s) in RCA: 88] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2008] [Accepted: 04/08/2009] [Indexed: 02/07/2023]
Abstract
BACKGROUND Interleukin-6 (IL-6) is known to be a multifunctional cytokine and IL-10 is an immunosuppressive factor. Both have been reported to be related to the disease prognosis in some human solid tumors. In the present study, we evaluated the clinical significance of preoperative serum IL-6 and IL-10 levels as new tumor markers in patients with gastric cancer (GC). METHODS Preoperative serum samples from 90 patients with GC and 9 normal healthy volunteers were assayed. Levels of IL-6 and IL-10 were determined by enzyme-linked immunosorbent assay (ELISA). The clinical significance of serum IL-6 and IL-10 levels was evaluated and compared with serum carcinoembryonic antigen (CEA) levels and serum C-reactive protein (CRP) levels in these patients. RESULTS The serum level of IL-6 was significantly higher in the GC patients than in the healthy subjects. Serum IL-6 levels were strongly correlated with CRP levels, but did not correlate with CEA or carbohydrate antigen (CA) 19-9 levels. Serum IL-10 levels did not correlate with CEA, CA19-9, or CRP. Strong positive correlations between serum IL-6 levels and tumor size and tumor stage were observed. On the other hand, IL-10 did not correlate with such clinicopathological findings of tumors. However, high serum IL-10 levels were associated with a worse prognosis in the GC patients, independently of their tumor stage. CONCLUSION These findings indicate that serum IL-6 may suggest gastric cancer progression. On the other hand, IL-10 may play an important role in host immunity and the prognosis of GC patients.
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Affiliation(s)
- Masahide Ikeguchi
- Department of Surgery, Division of Surgical Oncology, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, 683-8504, Japan
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Abstract
INTRODUCTION Recent research has suggested that serum tumor markers can give valuable prognostic information in gastric cancer. In this study, we examined the relationship between preoperative serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, CA 72-4, and alfa fetoprotein (AFP) levels on clinicopathologic significance in gastric cancer patients. METHODS Preoperative plasma levels of CEA, CA 19-9, CA 72-4, and AFP were retrospectively examined in 95 patients who underwent surgical resection for gastric cancer, and the prognostic value of the tumour markers were estimated. RESULTS The percentage of CA 19-9, CA 72-4, CEA, and AFP-positive cases were 41%, 32.6%, 24.2%, and 8.4%, respectively. CEA was more frequently positive in the patients with liver metastases (P=0.02). CA 19-9 was more frequently positive in patients with lymph node (P=0.005), peritoneal (P=0.01), and serosal (P=0.03) involvement. CA 72-4 was more frequently positive in patients with lymph node (P=0.01), peritoneal (P=0.03), and liver (P=0.01) involvement. Low 3-year cumulative survival was associated significantly with elevated serum levels of CEA (P=0.001), CA 19-9 (P=0.001), CA 72-4 (P=0.001), and AFP (P=0.01). In multivariate analysis, age, tumor stage, and CA 72-4 were the only independent prognostic factors. Being positive for CA 72-4 was associated with a 3.8-fold higher risk of death (95% confidence intervals: 1.3, 10.9). CONCLUSION Our results suggest that high preoperative serum levels of CA 72-4 in gastric cancer patients are associated with a higher risk of death due to gastric cancer.
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Kolesnikova EV, Tamkovich SN, Bryzgunova OE, Shelestyuk PI, Permyakova VI, Vlassov VV, Tuzikov AS, Laktionov PP, Rykova EY. Circulating DNA in the Blood of Gastric Cancer Patients. Ann N Y Acad Sci 2008; 1137:226-31. [DOI: 10.1196/annals.1448.009] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Aspinall-O'Dea M, Costello E. The pancreatic cancer proteome - recent advances and future promise. Proteomics Clin Appl 2007; 1:1066-79. [DOI: 10.1002/prca.200700144] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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