1.p53 Mutations and Microsatellite Instabilities in the Subtype of Intestinal Metaplasia of the Stomach.
Sung Soo KIM ; Choon Sang BHANG ; Ki Ouk MIN ; Hiun Suk CHAE ; Sang Wook CHOI ; Chang Don LEE ; Keun Woo LIM ; In Sik CHUNG ; Doo Ho PARK
Journal of Korean Medical Science 2002;17(4):490-496
To investigate the potential implication of the subtype of intestinal metaplasia in the progression to the gastric carcinoma, we analyzed the mutations of the p53 gene and microsatellite instability (MSI) both in the complete type (type I) and in the sulphomucin-secreting incomplete type (type III) intestinal metaplasia located adjacent to the gastric carcinoma. p53 mutations were observed in 13.3% of type I, in 6.6% of type III intestinal metaplasia, and in 40% of gastric carcinoma. The difference between p53 mutations observed in type I and type III intestinal metaplasia was not statistically significant. No identical mutation of the p53 gene was found in the intestinal metaplasia and carcinoma specimens from the patients. There was no case of intestinal metaplasia showing MSI. In gastric carcinomas, MSI was observed in six cases (40%). The cases harboring BAT-26 instability did not have the mutation of the p53 gene. These data suggest that intestinal metaplasia adjacent to gastric carcinoma, irrespective of its subtype, do not have the genetic alterations as showing in their carcinoma tissues.
Carcinoma/genetics/pathology
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Exons
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*Genes, p53
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Humans
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Metaplasia/genetics/pathology
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*Microsatellite Repeats
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*Mutation
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Precancerous Conditions
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Stomach/*pathology
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Stomach Neoplasms/genetics/pathology
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Tumor Suppressor Protein p53/genetics/metabolism
2.Germline polymorphisms of Bat26 and its significance in gastric cancer microsatellite instability.
Bing-jian LU ; Mao-de LAI ; Qiong HUANG ; Hong-qiang SHENG
Journal of Zhejiang University. Medical sciences 2005;34(4):353-357
OBJECTIVETo detect the germline polymorphic variations of Bat26 in Chinese and its significance in microsatellite instability (MSI) study of gastric cancers.
METHODSBat26 was analyzed by PCR-based denatured polyacrymide gel electrophoresis-silver stain method in peripheral blood from 389 healthy people and 34 gastric cancers with matched normal mucosa. Eleven other microsatellite loci were also detected for gastric cancers.
RESULT(1) No Bat26 variations were identified in 423 genomic DNA from peripheral blood or normal mucosa by polyacrymide gel electrophoresis. (2) Two MSI-H cancers, oth Bat26+, were detected in 34 cases of gastric cancer. The alterations of Bat26 and MSI-H status were identical (P<0.05). (3) Compared with those of RER-cancers, MSI-H (RER+)cancers showed more obvious infiltration of intraepithelial lymphocytes and peri-tumoral lymphocytes, and more pushing borders (P<0.05).
CONCLUSION(1) The germline polymorphisms of Bat26 in Chinese people are quasimonomorphic. Thus, no matched genomic DNA is needed while Bat26 was selected for tumor MSI analysis. (2) Bat26 is an independent indicator of MSI-H gastric cancers with distinct clinicopathological features.
Chromosomal Instability ; genetics ; Humans ; Microsatellite Repeats ; genetics ; Polymorphism, Genetic ; Stomach Neoplasms ; genetics ; pathology
3.Genetic instability in cancer tissues analyzed by random amplified polymorphic DNA PCR.
Jianxun WANG ; Qianwen WANG ; Feng YE
Chinese Medical Journal 2002;115(3):430-432
OBJECTIVETo detect DNA and chromosomes instabilities during the progression of tumors and screen new molecular markers coupled to putative or unknown oncogenes and/or tumor suppressor genes.
METHODSFive kinds of tumors, in a total of 128 specimens, were analyzed by random amplified polymorphic DNA (RAPD) PCR. Bands representing instabilities were recovered, purified, and cloned, labeled as probes for Southern and Northern blot analysis and DNA sequencing.
RESULTSSample 5 and 3 of the gastric cancer tissues showed the highest genomic changes and the average detectability in five cancers was up to at least 40% (42.2% - 49.4%). There were significant differences in the ability of each primer to detect genomic instability, which ranged from 27% (primer 8) to 68% (primer 2). Band B is a single copy fragment, and was found to be an allelic loss in gastric and colon cancers. It is a novel sequence and was registered in GenBank with Accession Number AF151005. Further analysis revealed that it might be part of a cis-regulatory element of a new tumor suppressor gene, containing a promoter of cis-action "CACA" box, an enhancer of "GATA" family and a start codon.
CONCLUSIONSIt was impossible or difficult to get great achievements for cancer treatments with the procedure of gene therapy only to one oncogene or one tumor suppressor gene because the extensive DNA variations occurred during the progression of tumor. RAPD assay connected with other techniques was a good tool for the detection of genomic instabilities and direct screening of some new molecular markers related to tumor suppressor genes or oncogenes.
Base Sequence ; Blotting, Southern ; Colonic Neoplasms ; genetics ; pathology ; Humans ; Liver Neoplasms ; genetics ; pathology ; Lung Neoplasms ; genetics ; pathology ; Molecular Sequence Data ; Neoplasms ; genetics ; pathology ; Polymorphism, Restriction Fragment Length ; Random Amplified Polymorphic DNA Technique ; Sequence Analysis, DNA ; Stomach Neoplasms ; genetics ; pathology
4.Effect of blocking endogenous miR-23a on the proliferation and invasion in gastric adenocarcinoma cell line MGC803.
Lihua ZHU ; Jiali TIAN ; Li CHEN ; Meimei WANG ; Yanan XIONG ; Guangling ZHANG ; Shuying LI ; Lijie YUAN
Journal of Southern Medical University 2013;33(5):678-683
OBJECTIVETo investigate the effect of functional blocking of endogenous miR-23a with a specific antisense oligonucleotide (ASO) on the proliferation and invasiveness of gastric adenocarcinoma cell line MGC803 in vitro.
METHODSA specific ASO targeting miR-23a, namely ASO-23a, was transfected into MGC803 cells to block endogenous miR-23a. The mRNA level of miR-23a in the transfected cells was detected with quantitative real-time PCR. The changes of cell proliferation following the transfection were detected with MTT assay and colony formation assay, and TUNEL assay and Transwell assay were employed to evaluate the changes in cell apoptosis and invasiveness, respectively.
RESULTSQuantitative real-time PCR demonstrated efficient functional blocking of endogenous miR-23a in MGC803 cells by ASO-23a. Suppression of miR-23a with ASO-23a obviously inhibited cell growth, colony formation and invasiveness of MGC803 cells and significantly enhanced the cell apoptosis.
CONCLUSIONASO-23a can efficiently block the function of endogenous miR-23a in MGC803 cells to inhibit cell proliferation and invasion and promote cell apoptosis.
Adenocarcinoma ; genetics ; pathology ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Humans ; MicroRNAs ; genetics ; Oligonucleotides, Antisense ; Stomach Neoplasms ; genetics ; pathology ; Transfection
5.MiR-4484 regulates the expression of integrin α 6 in gastric cancer tissues and its significance.
Hui Yu ZHONG ; Yuan ZHONG ; Yang WEN ; Xin Tong TAO ; Xing Bo SONG ; Xiao Jun LU
Chinese Journal of Oncology 2022;44(3):246-251
Objective: To investigate the relationship between the expression of integrin α 6 (ITGA6), miR-4484 and the pathologic stage of gastric cancer. Methods: Gastric cancer tissues and normal gastric mucosa tissues adjacent to cancer (>5 cm from tumor margin) of 30 patients with primary gastric cancer who underwent direct surgical resection without adjuvant therapy from June to September 2017 in West China Hospital of Sichuan University were selected. Real-time quantitative polymerase chain reaction (PCR) was used to detect the expression levels of miR-4484 and ITGA6, western blot was used to detect the expression level of ITGA6 protein, dual luciferase reporter gene was used to verify the relationship between ITGA6 and miR-4484. Spearman's correlation analysis was used to determine the relationship between miR-4484 and ITGA6 expression levels in gastric cancer tissues. Results: The expression level of ITGΑ6 in gastric cancer (32.30±13.47) was higher than that in matched normal gastric tissues (24.55±10.25, P=0.015), the area under the receiver operating characteristic (ROC) curve was 0.660 and the diagnostic sensitivity and specificity were 43.3% and 96.7%, respectively. The expression level of miR-4484 in gastric cancer (4.11±2.87) was lower than that of matched normal gastric tissues (5.75±2.80, P=0.029), the area under the ROC curve was 0.690 and the diagnostic sensitivity and specificity were 30.0% and 86.7%, respectively. The expression level of miR-4484 was negatively correlated with ITGA6 in gastric cancer tissues (r=-0.621, P<0.001). The expression level of ITGA6 protein in gastric cancer tissues (0.65±0.19) was higher than that in normal adjacent tissues (0.26±0.12, P<0.001). Compared with ITGA6 3'UTR wild-type+ miR-NC group, ITGA6 3'UTR wild-type+ miRNA mimics group had lower luciferase activity (50.69±5.10, 34.00±1.19, P<0.001), while the luciferase activity of ITGA6 3'UTR wild-type+ ASO miR-4484 group was higher than that of ITGA6 3'UTR wild-type+ miR-NC group (82.44±6.37, 50.69±5.10, P<0.001), indicated that ITGA6 was the direct target gene of miR-4484. The expression levels of miR-4484 in T1, T2, T3 and T4 (4a and 4b) gastric cancer tissues were 9.98±2.24, 5.28±2.03, 2.92±2.04 and 4.11±2.87, respectively, with statistical significance (P<0.001). The expression levels of ITGA6 in N0, N1, N2 and N3 gastric cancer tissues were 29.55±8.32, 21.71±3.75, 24.60±8.79 and 40.69±15.83, respectively, with statistical significance (P=0.022). The expression levels of miR-4484 in N0, N1, N2 and N3 gastric cancer tissues were 5.01±3.52, 5.48±2.76, 5.88±1.83 and 2.30±1.56, respectively, with statistical significance (P=0.032). The expression levels of ITGA6 in M0 and M1 gastric cancer tissues were 26.28±7.66 and 52.08±8.12, respectively, with statistical significance (P<0.001). The expression levels of miR-4484 in M0 and M1 gastric cancer tissues were 4.95±2.74 and 1.34±0.80, respectively, with statistical significance (P<0.001). Conclusions: ITGA6 is upregulated in gastric cancer tissues, while miR-4484 is downregulated in the gastric cancer group, and its expression level is related to the clinicopathological features of gastric cancer. ITGA6 is the direct target gene of miR-4484, implicates that miR-4484 may inhibit the invasion and metastasis of gastric cancer by regulating the expression of ITGA6. Both miR-4484 and ITGA6 may be the new prognostic markers and potential therapeutic targets of gastric cancer.
3' Untranslated Regions
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China
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Humans
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Integrin alpha6/genetics*
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MicroRNAs/genetics*
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Stomach Neoplasms/pathology*
6.Adenocarcinoma arising in gastroesophageal junction: a reappraisal.
Chinese Journal of Pathology 2007;36(6):363-365
Adenocarcinoma
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classification
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genetics
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pathology
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surgery
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Cardia
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Esophageal Neoplasms
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classification
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genetics
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pathology
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surgery
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Esophagogastric Junction
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pathology
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Humans
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Lymphatic Metastasis
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Neoplasm Invasiveness
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Stomach Neoplasms
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classification
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genetics
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pathology
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surgery
7.Diagnostic methods for peritoneal molecular residual disease in gastric cancer.
Tong Bo WANG ; Zheng LI ; Dong Bing ZHAO
Chinese Journal of Gastrointestinal Surgery 2023;26(5):419-422
Peritoneal metastasis of gastric cancer serving as the most frequent form of metastasis, is one of the leading causes of death. A portion of surgically treated patients often suffer from small peritoneal residual metastasis, which will lead to recurrence and metastasis of gastric cancer patients after surgery. Given these, the prevention and treatment of peritoneal metastasis of gastric cancer deserves more attention. Molecular residual disease (MRD) refers to the molecular abnormalities of tumor origin that cannot be found by traditional imaging or other laboratory methods after treatment, but can be found by liquid biopsy, representing the possibility of tumor persistence or clinical progress. In recent years, the detection of MRD based on ctDNA has gradually become a research hotspot in the prevention and treatment of peritoneal metastasis. Our team established a new method for MRD molecular diagnosis of gastric cancer, and reviewed the research achievements in this field.
Humans
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Stomach Neoplasms/pathology*
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Peritoneal Neoplasms/secondary*
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Liquid Biopsy
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Neoplasm, Residual/genetics*
8.DNA ploidy patterns in gastric adenocarcinoma.
Journal of Korean Medical Science 2000;15(2):159-166
To assess the value of DNA ploidy, flow cytometric analysis was performed on unfixed fresh materials obtained from 86 patients with gastric cancer who underwent stomach resection. We evaluated the DNA content of gastric carcinoma cells from four different sites and compared it with Ki-67 proliferating activity, and other pathologic parameters. The incidence of aneuploid and diploid was similar (48.8% vs. 51.1%). Early gastric carcinoma showed a higher rate of the diploid pattern (75%) compared to that of advanced gastric carcinoma 7.3%). DNA diploidy was noted increasingly in diffuse-type tumors according to uren, in signet ring cell type tumor according to WHO classification and in orly differentiated tumors (p<0.05). Well and moderately differentiated rcinomas revealed the aneuploid pattern more frequently than poorly fferentiated tumors. The aneuploidy was associated with high S phase fraction d high proliferative index. Aneuploidy was noted in the mucosa adjacent to the mor (26%), in the close normal-looking mucosa (7%) and in the remote rmal-looking mucosa (3%). This result suggest the possible role of field ncerization in the development of gastric adenocarcinoma.
Adenocarcinoma/pathology*
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Adenocarcinoma/genetics*
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Adenocarcinoma/chemistry
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Aged
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Aneuploidy*
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Cell Differentiation
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Cell Division
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Female
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Flow Cytometry
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Gastric Mucosa/pathology
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Human
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Ki-67 Antigen/analysis
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Male
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Middle Age
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Stomach Neoplasms/pathology*
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Stomach Neoplasms/genetics*
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Stomach Neoplasms/chemistry
9.Extent of field change in colorectal cancers with BRAF mutation.
Aaron POH ; Heidi Sian Ying CHANG ; Kok Yang TAN ; Xin Xiu SAM ; Avery KHOO ; Shoa Nian CHOO ; Min En NGA ; Wei Keat WAN
Singapore medical journal 2018;59(3):139-143
INTRODUCTIONSporadic colorectal cancers with BRAF mutations constitute two distinct subgroups of colorectal cancers. Recent studies have linked the presence of the BRAF mutation to a familial inheritance pattern. This was a proof-of-concept study that aimed to examine: (a) the extent of field change in sporadic colorectal cancers with BRAF mutation; and (b) the extent of resection margins required and the pattern of DNA mismatch repair protein loss in these tumours.
METHODSEight microsatellite instability-high tumours with positive BRAF mutation from an existing histopathological database were selected for BRAF mutation and mismatch repair protein analysis.
RESULTSAll the resection margins were negative for BRAF mutation. Three tumours had loss of MLH1 and PMS2 expressions, and five tumours had no protein loss. Six peritumoral tissues were negative and one was positive for BRAF mutation.
CONCLUSIONThe results suggest that any early field change effect is restricted to the immediate vicinity of the tumour and is not a pan-colonic phenomenon. Current guidelines on resection margins are adequate for BRAF mutation-positive colorectal cancers. Any suggestion of a hereditary link to these tumours is likely not related to germline BRAF gene mutations. The pattern of protein loss reinforces previous findings for the two subgroups of BRAF mutation-positive colorectal cancers.
Colorectal Neoplasms ; genetics ; pathology ; Female ; Humans ; Male ; Microsatellite Instability ; Mutation ; Neoplasm Metastasis ; Peritoneal Neoplasms ; pathology ; secondary ; Proto-Oncogene Proteins B-raf ; genetics ; Stomach Neoplasms ; pathology ; secondary
10.Prognostic and clinical value of Sirt1 expression in gastric cancer: A systematic meta-analysis.
Bin JIANG ; Jin-huang CHEN ; Wen-zheng YUAN ; Jin-tong JI ; Zheng-yi LIU ; Liang WU ; Qiang TANG ; Xiao-gang SHU
Journal of Huazhong University of Science and Technology (Medical Sciences) 2016;36(2):278-284
Many studies have reported that the expression of silent information regulator 1 (Sirt1) is associated with the clinical features and prognosis of patients with gastric cancer, but the exact function remains controversial. We conducted this study to illustrate the clinical and prognostic value of Sirt1 in gastric cancer. The related publications before December 2015 were searched in the databases including Pubmed, Cochrane Library, Embase and China National Knowledge Infrastructure (CNKI). The studies were included and excluded according to the inclusion criteria and exclusion criteria. The 3- and 5-year overall survival (OS) and clinical features such as age, T stage, N stage and differentiation were analyzed by software RevMan 5.3. A total of 1650 patients in 7 studies were included according to the inclusion criteria and exclusion criteria. The high expression of Sirt1 was found in 58.4% cases by immunohistochemistry. High expression of Sirt1 was closely linked with the 3-year OS (OR=0.25, 95% CI: 0.16-0.39, P<0.00001, fixed), patient's age (≥60 years old vs. <60 years old; OR=1.43, 95% CI: 1.06-1.93, P=0.02, fixed), T stage (T3+T4 vs. T1+T2; OR=1.45, 95% CI: 1.08-1.94, P=0.01, fixed), N stage (N1+N2+N3 vs. N0; OR=3.47, 95% CI: 2.39-5.05, P<0.00001, fixed) and tumor differentiation (G1+G2 vs. G3; OR=0.50, 95% CI: 0.35-0.69, P<0.0001, fixed). Nevertheless, it seemed that high expression of Sirt1 was not associated with 5-year OS (OR=0.44, 95% CI: 0.15-1.28, P=0.13, random). It was suggested that the high expression of Sirt1 implies a poor prognosis of gastric cancer patients in a relatively short period (3 years), but not in a long time (≥5 years). The expression of Sirt1 is also linked with patients' age, T stage, N stage and tumor differentiation.
Biomarkers, Tumor
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genetics
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metabolism
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Carcinoma
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metabolism
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pathology
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Humans
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Middle Aged
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Sirtuin 1
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genetics
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metabolism
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Stomach Neoplasms
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metabolism
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pathology
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Survival Analysis