|
1
|
Cahyanur R, Utari AP, Rahadiani N. Cyclin D1 expression, clinicopathological characteristics, and 2-year survival rate of gastric cancer in Cipto Mangunkusumo General Hospital. Niger J Clin Pract 2023; 26:1057-1062. [PMID: 37635596 DOI: 10.4103/njcp.njcp_222_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/29/2023]
Abstract
Background Cyclin D1 is a protein that can increase the proliferation of cancer cells. Its expression has been found in various malignancies, including gastric cancer. Cyclin D1 examinations have not been routinely performed for gastric cancer cases in Indonesia. A recent study of cyclin D1 in gastric cancer was associated with lymph node involvement, metastasis, poor prognosis, and a lack of response to platinum chemotherapy. Aim This study aimed to determine the relationships among cyclin D1 expression, clinicopathological features, and 2-year survival rates in gastric cancer. Materials and Methods This retrospective cohort study used medical records and paraffin blocks of patients suffering from gastric cancer at Cipto Mangunkusumo General Hospital, Jakarta, between 2015 and 2020. Data analysis was performed using Statistical Package for the Social Sciences (SPSS) version 20. The data were collected from 39 subjects, most of whom experienced eating disorder (69.23%), weight loss (76.92%), melena (53.85%), and anemia (51.28%). Tumor location was mostly found in the cardia and corpus of the gaster. Results This study found that the proportion of overexpression of cyclin D1 was 30.77%. Cyclin D1 expression was greater in subjects with liver metastases (50% vs. 14.8%, P = 0.04). Cyclin D1 expression was not associated with tumor location, tumor, node, and metastasis (TNM) stage, or histopathological findings. Analysis of the 2-year survival rate did not find any differences between patients with cyclin D1 overexpression and those with cyclin D1 negative. Conclusions Cyclin D1 expression was associated with liver metastases in patients with gastric cancer.
Collapse
Affiliation(s)
- R Cahyanur
- Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia - Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - A P Utari
- Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia - Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - N Rahadiani
- Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia - Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| |
Collapse
|
|
2
|
Lv H, Zhou D, Liu G. PVT1/miR-16/CCND1 axis regulates gastric cancer progression. Open Med (Wars) 2023; 18:20220550. [PMID: 36760720 PMCID: PMC9896163 DOI: 10.1515/med-2022-0550] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 08/03/2022] [Accepted: 08/10/2022] [Indexed: 02/03/2023] Open
Abstract
Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) has been reported to be a vital modulator in tumorigenesis of gastric cancer (GC). However, the detailed regulatory mechanism of PVT1 in GC remains largely unclear. In this work, the expressions of PVT1 and microRNA-16 (miR-16) were detected by quantitative real-time PCR (qRT-PCR) in GC tissues and cell lines. GC cell lines NCI-N87 and MKN45 cell lines were chosen for the following assays. After PVT1 was overexpressed or depleted, CCK-8 and Transwell assays were performed to examine the cell viability and invasive capacity. Cell cycle was analyzed by flow cytometry. The expression of cyclin D1 (CCND1) at mRNA and protein levels was measured by qRT-PCR and western blot. The competitive endogenous RNA molecular mechanism among PVT1, miR-16 and CCND1 was verified by bioinformatics analysis, luciferase-reporter gene assay and RNA immunoprecipitation assay. In the present study, it was revealed that PVT1 expression was remarkably evaluated in GC tissues and cell lines than that in the corresponding control group. PVT1 positively regulated the proliferation, migration and cell cycle progression of GC cells. Besides, miR-16 was identified as a target of PVT1, and CCND1 was identified as a target of miR-16. The depletion of PVT1 promoted the expression of miR-16 and suppressed CCND1 expression. Moreover, either miR-16 inhibitor or CCND1 overexpression plasmid could reverse the promoting effects of PVT1 on the malignant biological behaviors of GC cells. In conclusion, PVT1 promoted CCND1 expression by negatively regulating miR-16 expression to enhance the viability, invasion and cell cycle progression of GC cells.
Collapse
Affiliation(s)
- Haidong Lv
- Department of Tumor Surgery, Qinghai People’s Hospital, Xining810007, Qinghai, China
| | - Dixia Zhou
- Department of Tumor Surgery, Qinghai People’s Hospital, Xining810007, Qinghai, China
| | - Guoqing Liu
- Department of Tumor Surgery, Qinghai People’s Hospital, Republic Road No. 2, Xining810007, Qinghai, China
| |
Collapse
|
|
3
|
Xie W, Wang B, Wang X, Hou D, Su H, Huang H. Nine hub genes related to the prognosis of HBV-positive hepatocellular carcinoma identified by protein interaction analysis. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:478. [PMID: 32395522 PMCID: PMC7210132 DOI: 10.21037/atm.2020.03.94] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Background Hepatocellular carcinoma (HCC) represents the second highest cause of cancer-associated deaths worldwide, and hepatitis B virus (HBV) infection is a major risk factor. Here, we aimed to identify genetic signatures of HBV-positive (HBV+) HCC and uncover potential carcinogenic mechanisms. Methods Gene expression profiles of 124 HBV-positive samples, including tumor and non-tumor tissues were subjected to bioinformatics analysis. The expression levels of thymidylate synthase (TYMS) and CDC45 in patients’ samples were validated by immunohistochemistry (IHC) and their association with patient survival was assessed by the Kaplan-Meier method. Results A total of 666 differentially expressed genes (DEGs) were identified. The 137 upregulated genes were mainly enriched in the cell cycle, P53 signaling pathway, and extracellular matrix-receptor interaction, whereas the 529 downregulated genes were enriched in cytochrome P450 xenobiotic and drug metabolism, and cytokine-cytokine receptor interaction. A total of 15 hub genes were identified from the protein-protein interaction (PPI) network and 10 of them were strongly associated with HBV+ HCC. The expression of 9 hub genes (CDK1, NDC80, TYMS, AURKA, FOXM1, CDC45, ZWINT, PBK, and TPX2) was associated with poor overall survival. Validation of TYMS and CDC45 protein expression levels in clinical samples by IHC showed that they were higher in HBV+ HCC than in HBV- HCC or normal tissue and were associated with poor patient survival. Conclusions HBV may induce HCC through regulation of host gene expression. Among the hub DEGs identified, 9 key genes could be used as new prognostic biomarkers and treatment targets for HBV+ HCC.
Collapse
Affiliation(s)
- Wenhui Xie
- Graduate School, Fujian Medical University, Fujian Medical University Union Hospital, Fuzhou 350001, China
| | - Bin Wang
- Clinical Laboratory, Fujian Children's Hospital, Fujian Maternity and Child Health Hospital, Fuzhou 350001, China
| | - Xiaoting Wang
- Central Laboratory, Fujian Medical University Union Hospital, Fuzhou 350001, China
| | - Diyu Hou
- Central Laboratory, Fujian Medical University Union Hospital, Fuzhou 350001, China
| | - Huiyan Su
- Graduate School, Fujian Medical University, Fujian Medical University Union Hospital, Fuzhou 350001, China
| | - Huifang Huang
- Central Laboratory, Fujian Medical University Union Hospital, Fuzhou 350001, China
| |
Collapse
|
|
4
|
Wang Q, Li F, Liao Z, Li K, Yang X, Lin Y, Zhao Y, Weng S, Xia Y, Ye Y, Li S, Wang C, Lin Y. Low level of Cyclin-D1 correlates with worse prognosis of clear cell renal cell carcinoma patients. Cancer Med 2019; 8:4100-4109. [PMID: 31183974 PMCID: PMC6675723 DOI: 10.1002/cam4.2313] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2019] [Revised: 05/08/2019] [Accepted: 05/15/2019] [Indexed: 12/19/2022] Open
Abstract
Cyclin-D1 (CCND1) belongs to the highly conserved cyclin family whose members are characterized by abundant expression during the cell cycle. As an oncogene, high level of CCND1 was observed and related to poor prognosis and tumor recurrence in many cancers. In this study, we focused on the role of CCND1 in the clinical outcome of clear cell renal cell carcinoma (ccRCC). Gene Expression Omnibus database, The Cancer Genome Atlas database, and immunohistochemical staining were used. The mRNA and protein levels of CCND1 were significantly enhanced in ccRCC tumor tissues. However, the low level of CCND1, but not high level of CCND1, was related to poor prognosis and tumor recurrence in ccRCC. Further analysis showed that CCND1 mRNA level decreased with increasing ccRCC tumor grades and the rate of recurrence in ccRCC patients. In a nomogram model, the CCND1 mRNA level was shown to help predict ccRCC patient recurrence. CCND1 is a strong determinant for prediction of recurrence. The patients with high CCND1 level appear to have a more favorable prognosis together with more frequent low-grade tumors and low rate of recurrence. This is the first study to investigate the prognostic roles of CCND1 in ccRCC and discovered that CCND1 had an unconventional positive impact on the clinical outcome of ccRCC patients.
Collapse
MESH Headings
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Carcinoma, Renal Cell/diagnosis
- Carcinoma, Renal Cell/genetics
- Carcinoma, Renal Cell/metabolism
- Carcinoma, Renal Cell/pathology
- Cyclin D1/genetics
- Cyclin D1/metabolism
- Down-Regulation
- Female
- Gene Expression Regulation, Neoplastic
- Humans
- Kidney Neoplasms/diagnosis
- Kidney Neoplasms/genetics
- Kidney Neoplasms/metabolism
- Kidney Neoplasms/pathology
- Male
- Neoplasm Grading
- Neoplasm Recurrence, Local/diagnosis
- Neoplasm Recurrence, Local/genetics
- Neoplasm Recurrence, Local/metabolism
- Neoplasm Recurrence, Local/pathology
- Nomograms
- Prognosis
Collapse
Affiliation(s)
- Qing‐shui Wang
- Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Key Laboratory of Opto Electronic Science and Technology for Medicine of Ministry of Education, College of Life SciencesFujian Normal UniversityFuzhouP.R. China
| | - Feng Li
- Department of PathologyProvincial Clinical Medical College of Fujian Medical UniversityFuzhouP.R. China
| | - Zi‐qiang Liao
- Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Key Laboratory of Opto Electronic Science and Technology for Medicine of Ministry of Education, College of Life SciencesFujian Normal UniversityFuzhouP.R. China
| | - Ke Li
- Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Key Laboratory of Opto Electronic Science and Technology for Medicine of Ministry of Education, College of Life SciencesFujian Normal UniversityFuzhouP.R. China
| | - Xin‐liu Yang
- Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Key Laboratory of Opto Electronic Science and Technology for Medicine of Ministry of Education, College of Life SciencesFujian Normal UniversityFuzhouP.R. China
| | - You‐yu Lin
- Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Key Laboratory of Opto Electronic Science and Technology for Medicine of Ministry of Education, College of Life SciencesFujian Normal UniversityFuzhouP.R. China
| | - Yi‐lin Zhao
- Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Key Laboratory of Opto Electronic Science and Technology for Medicine of Ministry of Education, College of Life SciencesFujian Normal UniversityFuzhouP.R. China
| | - Shu‐yun Weng
- Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Key Laboratory of Opto Electronic Science and Technology for Medicine of Ministry of Education, College of Life SciencesFujian Normal UniversityFuzhouP.R. China
| | - Yun Xia
- Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Key Laboratory of Opto Electronic Science and Technology for Medicine of Ministry of Education, College of Life SciencesFujian Normal UniversityFuzhouP.R. China
| | - Yan Ye
- Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Key Laboratory of Opto Electronic Science and Technology for Medicine of Ministry of Education, College of Life SciencesFujian Normal UniversityFuzhouP.R. China
| | - Su‐huan Li
- Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Key Laboratory of Opto Electronic Science and Technology for Medicine of Ministry of Education, College of Life SciencesFujian Normal UniversityFuzhouP.R. China
| | - Chen‐yi Wang
- Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Key Laboratory of Opto Electronic Science and Technology for Medicine of Ministry of Education, College of Life SciencesFujian Normal UniversityFuzhouP.R. China
| | - Yao Lin
- Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Key Laboratory of Opto Electronic Science and Technology for Medicine of Ministry of Education, College of Life SciencesFujian Normal UniversityFuzhouP.R. China
| |
Collapse
|
|
5
|
Xie ZC, Dang YW, Wei DM, Chen P, Tang RX, Huang Q, Liu JH, Luo DZ. Clinical significance and prospective molecular mechanism of MALAT1 in pancreatic cancer exploration: a comprehensive study based on the GeneChip, GEO, Oncomine, and TCGA databases. Onco Targets Ther 2017; 10:3991-4005. [PMID: 28860807 PMCID: PMC5558580 DOI: 10.2147/ott.s136878] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Purpose Long noncoding RNAs (lncRNAs) are known to function as regulators in the development and occurrence of various tumors. MALAT1 is a highly conserved lncRNA and has vital functions in diverse tumors, including pancreatic cancer (PC). However, the underlying molecular regulatory mechanism involved in the occurrence and development of PC remains largely unknown. Thus, it is important to explore MALAT1 in PC and elucidate its function, which might offer a new perspective for clinical diagnosis and therapy. Methods First, we used the Gene Expression Omnibus, Oncomine, and The Cancer Genome Atlas databases to determine the clinical diagnostic and prognostic values of MALAT1. We next used our own GeneChip and The Cancer Genome Atlas database to collect the possible target genes of MALAT1 and further utilized a bioinformatics analysis to explore the underlying significant pathways that might be crucial in PC. Finally, we identified several key target genes of MALAT1 and hope to offer references for future research. Results We found that the expression of MALAT1 was significantly elevated in patients with PC. A receiver operating characteristics curve analysis showed a moderate diagnostic value (area under the curve =0.75, sensitivity =0.66, specificity =0.72). A total of 224 important overlapping genes were collected, and six hub genes (CCND1, MAPK8, VEGFA, FOS, CDH1, and HSP90AA1) were identified, of which CCND1, MAPK8, and VEGFA, are important genes in PC. Several pathways, including the mTOR signaling pathway, pathways in cancer, and the MAPK signaling pathway, were suggested to be the vital MALAT1 pathways in PC. Conclusion MALAT1 is suggested to be a promising diagnostic biomarker in PC. Six hub genes (CCND1, MAPK8, VEGFA, FOS, CDH1, and HSP90AA1), and specifically CCND1, MAPK8, and VEGFA, might be key MALAT1 target genes in PC. Due to their possible clinical significance in PC, several pathways, such as the mTOR signaling pathway, pathways in cancer, and the MAPK signaling pathway, are worthy of further study.
Collapse
Affiliation(s)
| | | | | | | | | | | | - Jiang-Hua Liu
- Department of Pathology.,Department of Emergency Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | | |
Collapse
|
|
6
|
Shan YS, Hsu HP, Lai MD, Hung YH, Wang CY, Yen MC, Chen YL. Cyclin D1 overexpression correlates with poor tumor differentiation and prognosis in gastric cancer. Oncol Lett 2017; 14:4517-4526. [PMID: 28943959 PMCID: PMC5594254 DOI: 10.3892/ol.2017.6736] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Accepted: 04/24/2017] [Indexed: 12/17/2022] Open
Abstract
Overexpression of cyclin D is associated with the molecular tumorigenesis of gastric cancer. The purpose of the present study was to investigate the expression of cyclin D in human gastric cancer and to determine the potential correlations between cyclin D expression and clinicopathological characteristics of specific histological types, as well as its prognostic significance. In the present study, the expression of the cyclin D1 (CCND1), cyclin D2 (CCND2) and cyclin D3 (CCND3) genes in gastric cancer patients was explored using the Oncomine database, and their correlation with overall survival (OS) and progression-free survival (PFS) was evaluated using Kaplan-Meier analysis. The prognostic significance of CCND1 protein expression was evaluated by western blot analysis of 32 matched specimens of gastric adenocarcinomas and normal tissues obtained from patients treated at the National Cheng Kung University Hospital (Tainan, Taiwan). Analysis of the Oncomine cancer microarray database revealed that CCND1 gene expression was significantly increased in gastric intestinal-type adenocarcinoma, while CCND2 was significantly increased in diffuse gastric adenocarcinoma, gastric intestinal-type adenocarcinoma and gastric mixed adenocarcinoma. Kaplan-Meier analysis indicated that overexpression of CCND1 was associated with reduced OS and PFS. In addition, overexpression of CCND1 and downregulation of CCND2 were significantly correlated with receptor tyrosine-protein kinase erb-2-negative tumors and poor differentiation. The ratio of relative CCND1 expression (expressed as the CCND1/β-actin ratio) in tumor tissues compared with that in normal tissues was correlated with poor differentiation (P=0.0018). In summary, CCND1 overexpression is associated with shorter survival in patients with gastric cancer and with poorly differentiated tumors.
Collapse
Affiliation(s)
- Yan-Shen Shan
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan, R.O.C
| | - Hui-Ping Hsu
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan, R.O.C
| | - Ming-Derg Lai
- Department of Biochemistry and Molecular Biology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan, R.O.C
| | - Yu-Hsuan Hung
- Department of Biochemistry and Molecular Biology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan, R.O.C
| | - Chih-Yang Wang
- Department of Biochemistry and Molecular Biology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan, R.O.C
| | - Meng-Chi Yen
- Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, R.O.C
| | - Yi-Ling Chen
- Department of Senior Citizen Service Management, Chia Nan University of Pharmacy and Science, Tainan 71710, Taiwan, R.O.C.,Senior Citizen Development Center, Chia Nan University of Pharmacy and Science, Tainan 71710, Taiwan, R.O.C
| |
Collapse
|
|
7
|
Petkevicius V, Salteniene V, Juzenas S, Wex T, Link A, Leja M, Steponaitiene R, Skieceviciene J, Kupcinskas L, Jonaitis L, Kiudelis G, Malfertheiner P, Kupcinskas J. Polymorphisms of microRNA target genes IL12B, INSR, CCND1 and IL10 in gastric cancer. World J Gastroenterol 2017; 23:3480-3487. [PMID: 28596683 PMCID: PMC5442083 DOI: 10.3748/wjg.v23.i19.3480] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2016] [Revised: 02/23/2017] [Accepted: 03/21/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate associations between miRNA target genes IL12B, INSR, CCND1 and IL10 polymorphisms and gastric cancer (GC) in European population. METHODS Gene polymorphisms were analyzed in 508 controls and 474 GC patients from 3 tertiary centers in Germany, Lithuania and Latvia. Controls were patients from the out-patient departments, who were referred for upper endoscopy because of dyspeptic symptoms and had no history of previous malignancy. Gastric cancer (GC) patients had histopathological verification of gastric adenocarcinoma. Genomic DNA was extracted using salting out method from peripheral blood mononuclear cells. IL12B T>G (rs1368439), INSR T>C (rs1051690), CCND1 A>C (rs7177) and IL10 T>C (rs3024498) SNPs were genotyped by the real-time polymerase chain reaction. Associations between gene polymorphism and GC were evaluated using multiple logistic regression analysis with adjustment for sex, age and country of birth. RESULTS We observed similar distribution of genotypes and allelic frequencies of all polymorphisms between GC patients and controls except of INSR rs1051690. The frequency of the T allele of INSR gene was significantly higher in GC patients than in controls (23.26% and 19.19% respectively, P = 0.028). CT genotype was also more prevalent in patients compared to control group (38.48% and 30.12% respectively, P < 0.021). Logistic regression analysis revealed that only one polymorphism (rs1051690 in INSR gene) was associated with increased risk of GC. Carriers of CT genotype had higher odds of GC when compared to CC genotype (OR = 1.45, 95%PI: 1.08-1.95, P = 0.01). Similar association was observed in a dominant model for INSR gene, where comparison of TT+CT vs CC genotypes showed an increased risk of GC (OR = 1.44, 95%PI: 1.08-1.90, P = 0.01). Other analyzed SNPs were not associated with the presence of GC. CONCLUSION INSR rs1051690 SNP is associated with increased risk of GC, while polymorphisms in IL12B, CCND1 and IL10 genes are not linked with the presence of GC.
Collapse
|
|
8
|
Prognostic Importance of Cell Cycle Regulators Cyclin D1 ( CCND1) and Cyclin-Dependent Kinase Inhibitor 1B ( CDKN1B/p27) in Sporadic Gastric Cancers. Gastroenterol Res Pract 2016; 2016:9408190. [PMID: 27781065 PMCID: PMC5066010 DOI: 10.1155/2016/9408190] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Accepted: 09/01/2016] [Indexed: 12/14/2022] Open
Abstract
Background. Gastric cancer is known for a notable variety in the course of the disease. Clinical factors, such as tumor stage, grade, and localization, are key in patient survival. It is expected that molecular factors such as somatic mutations and gene amplifications are also underlying tumor biological behavior and may serve as factors for prognosis estimation. Aim. The purpose of this study was to examine gene amplifications from a panel of genes to uncover potential prognostic marker candidates. Methods. A panel of gene amplifications including 71 genes was tested by multiplex ligation-dependent probe amplification (MLPA) technique in 76 gastric cancer samples from a Caucasian population. The correlation of gene amplification status with patient survival was determined by the Kaplan-Meier method. Results. The amplification of two cell cycle regulators, CCND1 and CDKN1B, was identified to have a negative prognostic role. The medial survival of patients with gastric cancer displaying amplification compared to patients without amplification was 192 versus 725 days for CCND1 (P = 0.0012) and 165 versus 611 days for CDKN1B (P = 0.0098). Conclusion. Gene amplifications of CCND1 and CDKN1B are potential candidates to serve as prognostic markers for the stratification of patients based on the estimate of survival in the management of gastric cancer patients.
Collapse
|
|
9
|
Yu S, Li G, Wang Z, Wang Z, Chen C, Cai S, He Y. The prognostic value of pSTAT3 in gastric cancer: a meta-analysis. J Cancer Res Clin Oncol 2016; 142:649-57. [PMID: 26233579 DOI: 10.1007/s00432-015-2023-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2015] [Accepted: 07/22/2015] [Indexed: 12/13/2022]
Abstract
INTRODUCTION The prognostic value of pSTAT3 in gastric cancer has been assessed for years while the results remain controversial and heterogeneous. Therefore, we conducted this meta-analysis to determine the prognostic effect of pSTAT3 in gastric cancer patients. METHODS We searched PubMed, Embase and Web of Science and eight studies comprising 1314 gastric cancer patients were included in our meta-analysis. Hazard ratios (HRs) with 95 % confidence interval (95 % CI) were extracted to perform meta-analysis on the overall survival. Subgroup analysis according to study location, publication year, number of patients and quality score of studies were also investigated. RESULTS Our results revealed that pSTAT3-positive patients had a significant increase in mortality risk as compared to pSTAT3-negative patients in the random-effects model (combined HR 1.87, 95 % CI 1.28-2.74). However, our result showed no statistically significant association between pSTAT3 and clinicopathological characteristics (TMN stage, lymph node metastasis, grade of differentiation, Lauren classification and distant metastasis) of gastric cancer. CONCLUSION In conclusion, our meta-analysis suggests that positive expression of pSTAT3 is associated with poor prognosis in gastric cancer patients.
Collapse
Affiliation(s)
- S Yu
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, No. 58, Zhongshan 2nd Street, Guangzhou, 510080, Guangdong Province, People's Republic of China
| | - G Li
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, No. 58, Zhongshan 2nd Street, Guangzhou, 510080, Guangdong Province, People's Republic of China
| | - Z Wang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, No. 58, Zhongshan 2nd Street, Guangzhou, 510080, Guangdong Province, People's Republic of China.
| | - Z Wang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, No. 58, Zhongshan 2nd Street, Guangzhou, 510080, Guangdong Province, People's Republic of China
| | - C Chen
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, No. 58, Zhongshan 2nd Street, Guangzhou, 510080, Guangdong Province, People's Republic of China
| | - S Cai
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, No. 58, Zhongshan 2nd Street, Guangzhou, 510080, Guangdong Province, People's Republic of China
| | - Y He
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, No. 58, Zhongshan 2nd Street, Guangzhou, 510080, Guangdong Province, People's Republic of China
| |
Collapse
|
|
10
|
Kanda M, Kodera Y. Recent advances in the molecular diagnostics of gastric cancer. World J Gastroenterol 2015; 21:9838-9852. [PMID: 26379391 PMCID: PMC4566379 DOI: 10.3748/wjg.v21.i34.9838] [Citation(s) in RCA: 87] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2015] [Revised: 06/15/2015] [Accepted: 08/25/2015] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is the third most common cause of cancer-related death in the world, representing a major global health issue. Although the incidence of GC is declining, the outcomes for GC patients remain dismal because of the lack of effective biomarkers to detect early GC and predict both recurrence and chemosensitivity. Current tumor markers for GC, including serum carcinoembryonic antigen and carbohydrate antigen 19-9, are not ideal due to their relatively low sensitivity and specificity. Recent improvements in molecular techniques are better able to identify aberrant expression of GC-related molecules, including oncogenes, tumor suppressor genes, microRNAs and long non-coding RNAs, and DNA methylation, as novel molecular markers, although the molecular pathogenesis of GC is complicated by tumor heterogeneity. Detection of genetic and epigenetic alterations from gastric tissue or blood samples has diagnostic value in the management of GC. There are high expectations for molecular markers that can be used as new screening tools for early detection of GC as well as for patient stratification towards personalized treatment of GC through prediction of prognosis and drug-sensitivity. In this review, the studies of potential molecular biomarkers for GC that have been reported in the publicly available literature between 2012 and 2015 are reviewed and summarized, and certain highlighted papers are examined.
Collapse
|