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TGFB1 polymorphisms and TGF-?1 plasma levels identify gastric adenocarcinoma patients with lower survival rate and disseminated disease.

ABSTRACT: TGF-?1 is involved in tumour growth. Four TGFB1 SNPs and TGF-?1 production by stimulated PBMC were determined in seventy-eight gastric adenocarcinoma patients. In addition, TGF-?1 levels were measured in the plasma of further thirty patients. rs1800471-G/C genotype was prevalent in patients (20.7%) compared to controls (8.4%), as it also was the rs1800468 SNP-G/A genotype in stage IV patients (20.7%) compared to stage I, II and III patients, combined (10.3%). Conversely, the T/T rs1800469 SNP-T/T genotype was absent in the former group and present in 19.0% in the latter. Furthermore, the rs1800469-C/rs1800470-T (CT) haplotype was found in 15.0% of stage IV patients as compared to 3.0% of the remaining patients (3.0%) and also identifies patients with worse five-year life expectancy (P = .03). TGF-?1 synthesis by stimulated PBMCs was significantly lower in patients with the risk SNPs or haplotype, compared to the alternative genotype. Finally, TGF-?1 plasma levels were lower in patients with worse life expectancy. Analysis of TGFB1 SNPs and measurement of plasma TGF-?1 levels serves to identify patients at risk of developing a more aggressive disease.

SUBMITTER: Juarez I

PROVIDER: S-EPMC7812301 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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TGFB1 polymorphisms and TGF-β1 plasma levels identify gastric adenocarcinoma patients with lower survival rate and disseminated disease.

Juarez Ignacio I Gutierrez Alberto A Vaquero-Yuste Christian C Molanes-López Elisa M EM López Adela A Lasa Inmaculada I Gómez Remedios R Martin-Villa José Manuel JM

Journal of cellular and molecular medicine 20201204 2

TGF-β1 is involved in tumour growth. Four TGFB1 SNPs and TGF-β1 production by stimulated PBMC were determined in seventy-eight gastric adenocarcinoma patients. In addition, TGF-β1 levels were measured in the plasma of further thirty patients. rs1800471-G/C genotype was prevalent in patients (20.7%) compared to controls (8.4%), as it also was the rs1800468 SNP-G/A genotype in stage IV patients (20.7%) compared to stage I, II and III patients, combined (10.3%). Conversely, the T/T rs1800469 SNP-T/ ...[more]

PMID: 33274798

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Project description:BackgroundThe dynein axonemal heavy chain (DNAH) family of genes encode the dynein axonemal heavy chain, which is involved in cell motility. Genomic variations of DNAH family members have been frequently reported in diverse kinds of malignant tumors. In this study, we analyzed the genomic database to evaluate the mutation status of DNAH genes in gastric adenocarcinoma and further identified the significance of mutant DNAH genes as effective molecular biomarkers for predicting chemotherapy response in gastric cancer patients.MethodsWe analyzed the clinical and genomic data of gastric cancer patients published in The Cancer Genome Atlas (TCGA) project. Data on chemotherapy response, overall survival (OS) and chemotherapy-free survival were retrieved. Then, we verified the results via targeted sequencing of gastric cancer patients with similar clinical characteristics but different chemotherapeutic outcomes.ResultsIn total, 132 gastric adenocarcinoma patients undergoing chemotherapy treatment from TCGA were included in our study. Somatic mutations in all 13 members of the DNAH family of genes were associated with different chemotherapy responses. Compared with patients with wild-type DNAH genes (n = 59), a significantly higher proportion of those with mutations in DNAH genes (n = 73) (55.9% vs 80.8%) responded to chemotherapy (P = 0.002). Moreover, DNAH mutations were correlated with significantly better OS (P = 0.027), chemotherapy-free survival (P = 0.027), fluoropyrimidine-free survival (P = 0.048) and platinum-free survival (P = 0.014). DNAH mutation status was an independent risk factor for OS (P = 0.015), chemotherapy-free survival (P = 0.015) and platinum-free survival (P = 0.011). We identified somatic mutations in 27 (42.2%) of the 64 stage III gastric adenocarcinoma patients receiving fluoropyrimidine-based chemotherapy by targeted exon sequencing with strict screening conditions. In our own cohort, a significantly higher proportion of patients (n = 32) with DNAH mutations than patients with wild-type DNAH genes (n = 32) had a good prognosis (OS > 48 months) (70.4% vs 35.1%) (P = 0.005).ConclusionsDynein axonemal heavy chain gene mutations contribute positively to chemotherapy sensitivity in gastric cancer patients.

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TGFB1 polymorphisms and TGF-?1 plasma levels identify gastric adenocarcinoma patients with lower survival rate and disseminated disease.

Publications

TGFB1 polymorphisms and TGF-β1 plasma levels identify gastric adenocarcinoma patients with lower survival rate and disseminated disease.

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