Polymorphisms of an oncogenic gene, mesothelin, predict the risk and prognosis of gastric cancer in a Chinese Han population

Shen, Kuan; Liu, Kanghui; Wang, Yuanhang; Ni, Peidong; Xiao, Jian; Hong, Fan; Zhou, Xinyi; Xu, Zekuan; Yang, Li

doi:10.1007/s00204-022-03290-6

Cited by 7 publications

(6 citation statements)

References 43 publications

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“…All patients received medical treatment at the First Affiliated Hospital of Nanjing Medical University between February 2012 and March 2020. Exclusion criteria and detailed definitions are provided in a previous study [ 1 ].…”

Section: Methodsmentioning

confidence: 99%

“…Extraction of DNA was performed following our previous introductions [ 1 ]. The genotypes of the chosen tagSNPs were determined by the SNaPshot genotyping method, which has been validated in previous studies [ 21 , 22 ].…”

Section: Methodsmentioning

confidence: 99%

“…SPSS22.0 software (SPSS Inc., Chicago, IL, USA) was chosen for performing the statistical analysis in our research. Statistical methods were used as described in our previous studies [ 1 ].…”

Section: Methodsmentioning

confidence: 99%

“…Despite the availability of numerous potential therapies, GC remains the fifth most common cancer in terms of incidence and the fourth leading cause of cancer-related death worldwide, posing a significant threat to human health [ 1 ]. According to recent data, GC was responsible for 397,000 new cases and approximately 290,000 deaths in China in 2016 [ 2 ], most of whom were diagnosed at advanced stages.…”

Section: Introductionmentioning

confidence: 99%

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Polymorphism rs2327430 in TCF21 predicts the risk and prognosis of gastric cancer by affecting the binding between TFAP2A and TCF21

Zhou,

Shen,

Cao

et al. 2024

Cancer Cell Int

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Background Single nuclear polymorphisms (SNPs) have been published to be correlated with multiple diseases. Transcription Factor 21 (TCF21) is a critical transcription factor involved in various types of cancers. However, the association of TCF21 genetic polymorphisms with gastric cancer (GC) susceptibility and prognosis remains unclear. Methods A case-control study comprising 890 patients diagnosed with GC and an equal number of cancer-free controls was conducted. After rigorous statistical analysis, molecular experiments were carried out to elucidate the functional significance of the SNPs in the context of GC. Results TCF21 rs2327430 (OR = 0.78, P = 0.026) provides protection against GC, while rs4896011 (OR = 1.39, P = 0.005) exhibit significant associations with GC risk. Furthermore, patients with the (TC + CC) genotype of rs2327430 demonstrate a relatively favorable prognosis (OR = 0.47, P = 0.012). Mechanistically, chromatin immunoprecipitation assay and luciferase reporter assay revealed that the C allele of rs2327430 disrupts the binding of Transcription Factor AP-2 Alpha (TFAP2A) to the promoter region of TCF21, resulting in increased expression of TCF21 and inhibition of malignant behaviors in GC cells. Conclusion Our findings highlight the significant role of TCF21 SNPs in both the risk and prognosis of GC and provide valuable insights into the underlying molecular mechanisms. Specifically, the disruptive effect of rs2327430 on TCF21 expression and its ability to modulate malignant cell behaviors suggest that rs2327430 may serve as a potential predictive marker for GC risk and prognosis.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Polymorphism rs2327430 in TCF21 predicts the risk and prognosis of gastric cancer by affecting the binding between TFAP2A and TCF21

Zhou,

Shen,

Cao

et al. 2024

Cancer Cell Int

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“…The NHLBI Exome Sequencing Project (ESP) currently displays 217 variations in the MSLN gene for European/American populations. Several studies from Italy [ 16 , 17 , 18 , 19 ] and one each from Slovenia [ 20 ] and China [ 21 ] showed strong evidence that certain single-nucleotide polymorphisms (SNPs) in the MSLN promoter region and also the SNP MSLN rs1057147 have a modulating influence on the diagnostic impact of mesothelin levels. In this target region, multiple other SNPs exist, but a general problem in the promoter region of the MSLN gene is the presence of SNPs that are in a linkage disequilibrium.…”

Section: Introductionmentioning

confidence: 99%

Mesothelin Gene Variants Affect Soluble Mesothelin-Related Protein Levels in the Plasma of Asbestos-Exposed Males and Mesothelioma Patients from Germany

Rihs

Casjens

Raiko

et al. 2022

Biology

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Malignant mesothelioma (MM) is a severe disease mostly caused by asbestos exposure. Today, one of the best available biomarkers is the soluble mesothelin-related protein (SMRP), also known as mesothelin. Recent studies have shown that mesothelin levels are influenced by individual genetic variability. This study aimed to investigate the influence of three mesothelin (MSLN) gene variants (SNPs) in the 5′-untranslated promoter region (5′-UTR), MSLN rs2235503 C > A, rs3764246 A > G, rs3764247 A > C, and one (rs1057147 G > A) in the 3′-untranslated region (3′-UTR) of the MSLN gene on plasma concentrations of mesothelin in 410 asbestos-exposed males without cancer and 43 males with prediagnostic MM (i.e., with MM diagnosed later on) from the prospective MoMar study, as well as 59 males with manifest MM from Germany. The mesothelin concentration differed significantly between the different groups (p < 0.0001), but not between the prediagnostic and manifest MM groups (p = 0.502). Five to eight mutations of the four SNP variants studied were associated with increased mesothelin concentrations (p = 0.001). The highest mesothelin concentrations were observed for homozygous variants of the three promotor SNPs in the 5′-UTR (p < 0.001), and the highest odds ratio for an elevated mesothelin concentration was observed for MSLN rs2235503 C > A. The four studied SNPs had a clear influence on the mesothelin concentration in plasma. Hence, the analysis of these SNPs may help to elucidate the diagnostic background of patients displaying increased mesothelin levels and might help to reduce false-positive results when using mesothelin for MM screening in high-risk groups.

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Polymorphism rs1057147 located in mesothelin gene predicts lymph node metastasis in patients with gastric cancer

Shen

Cheng

Xiao

et al. 2023

Appl Microbiol Biotechnol

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Polymorphisms of an oncogenic gene, mesothelin, predict the risk and prognosis of gastric cancer in a Chinese Han population

Cited by 7 publications

References 43 publications

Polymorphism rs2327430 in TCF21 predicts the risk and prognosis of gastric cancer by affecting the binding between TFAP2A and TCF21

Polymorphism rs2327430 in TCF21 predicts the risk and prognosis of gastric cancer by affecting the binding between TFAP2A and TCF21

Mesothelin Gene Variants Affect Soluble Mesothelin-Related Protein Levels in the Plasma of Asbestos-Exposed Males and Mesothelioma Patients from Germany

Polymorphism rs1057147 located in mesothelin gene predicts lymph node metastasis in patients with gastric cancer

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