Pan-cancer prognostic value of TGFBR1: Bioinformatics and experimental validation with a focus on gastric cancer

Our plain-English summary of Pan-cancer prognostic value of TGFBR1: Bioinformatics and experimental validation with a focus on gastric cancer, by X. Zhao, L. Shen, Z. Gong, et al (Oncology Letters, 2026).

The study

• Authors: X. Zhao, L. Shen, Z. Gong, M. Lv, Y. Zhang, B. Tang, X. Li
• Journal: Oncology Letters
• Published: 2026;32(5):523
• Read it: PubMed · Publisher · Free full text

Abstract

TGF-β receptor 1 (TGFBR1) is a key component of TGF-β signaling and has been implicated in tumor progression. However, its expression patterns, prognostic relevance and associated molecular contexts vary among malignancies and remain incompletely characterized within a consistent pan-cancer framework. In the present study, TGFBR1 expression, clinicopathological associations, survival outcomes, immune and stromal infiltration, genomic features, co-expression profiles and transcriptional programs were systematically evaluated using The Cancer Genome Atlas (TCGA), TCGA-Genotype-Tissue Expression and complementary public datasets. Multivariable Cox regression was performed with adjustment for age, sex and pathological stage and the independent GSE15459 gastric cancer (GC) cohort was used for external prognostic validation and gene-set enrichment analysis. TGFBR1 exhibited cancer type-dependent expression alterations rather than uniform upregulation across malignancies. Higher TGFBR1 expression remained associated with poorer overall survival (OS) in mesothelioma (MESO), adrenocortical carcinoma (ACC) and kidney renal papillary cell carcinoma and with poorer disease-specific survival in ACC, esophageal carcinoma, MESO, lung squamous cell carcinoma, stomach adenocarcinoma and bladder urothelial carcinoma after multivariable adjustment. In GSE15459, elevated TGFBR1 expression was associated with shorter OS and remained significant after adjustment for age, sex, pathological stage and Lauren classification. TGFBR1 expression was also associated with distinct immune, stromal, genomic and transcriptional contexts across cancer types. In GC, enrichment analyses revealed an association between higher TGFBR1 expression and apoptosis- and stress-response-associated programs, epithelial cell proliferation, focal-adhesion assembly and actin-cytoskeleton organization. In vitro, TGFBR1 knockdown reduced the proliferation and migration of GC cells, altered epithelial-mesenchymal transition-associated protein expression and promoted apoptosis. Collectively, these findings define the cancer-type-specific clinical and biological relevance of TGFBR1 and support its prognostic importance in selected malignancies, particularly GC, while further mechanistic and prospective validation remains necessary.

Copyright: © 2026 Zhao et al.

In plain English

This study did not examine asbestos. The authors analyzed public gene-expression and survival data from The Cancer Genome Atlas (TCGA) and related databases, covering 34 cancer types including mesothelioma. They looked at how levels of the gene TGFBR1 (TGF-β receptor 1) related to patient survival. They also checked their findings in a separate set of 192 gastric adenocarcinoma samples (GSE15459) and ran laboratory experiments on gastric cancer cell lines. Higher TGFBR1 expression was associated with shorter overall survival in several cancers. After adjustment for age, sex and pathological stage, it remained associated with poorer overall survival in mesothelioma, adrenocortical carcinoma and kidney renal papillary cell carcinoma, and with poorer disease-specific survival in six cancers including mesothelioma. The article's text gives no hazard ratios for mesothelioma. In the gastric cohort, each one-standard-deviation increase in expression had an adjusted hazard ratio for death of 1.38 (95% CI 1.10 to 1.74). Reducing TGFBR1 in gastric cancer cells lowered their growth and migration. The authors concluded that the findings support TGFBR1's prognostic relevance in selected cancers, particularly gastric cancer. They called the immune, genomic and enrichment analyses exploratory.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Bioinformatics analysis of public cancer databases (pan-cancer), with external validation in one gastric cancer cohort and in vitro cell-line experiments
• Who was studied: Tumor and normal tissue samples from TCGA and GTEx public databases covering 34 cancer types, including mesothelioma; an independent gastric cancer cohort (GSE15459) of 192 gastric adenocarcinoma samples; human gastric cancer cell lines (YCCEL1, AGS and others) and a normal gastric mucosal cell line (GES-1)
• Exposure: No asbestos or fiber exposure was studied. The factor examined was the expression level of the TGFBR1 gene (high vs low by median, or per standard deviation). In the laboratory work, TGFBR1 was reduced (knocked down) in gastric cancer cells using siRNA.
• Main results:
  • TGFBR1 expression differed between tumor and normal tissue in a cancer-type-dependent way: higher in some cancers, lower in others.
  • In unadjusted (univariable) TCGA analyses, higher TGFBR1 expression was associated with shorter overall survival in several cancer types, including mesothelioma.
  • After adjustment for age, sex and pathological stage, TGFBR1 expression remained significantly associated with poorer overall survival in mesothelioma, adrenocortical carcinoma and kidney renal papillary cell carcinoma (no hazard ratios given in the text).
  • After the same adjustment, TGFBR1 expression was significantly associated with poorer disease-specific survival in adrenocortical carcinoma, esophageal carcinoma, mesothelioma, lung squamous cell carcinoma, stomach adenocarcinoma and bladder urothelial carcinoma.
  • In the independent gastric cancer cohort (GSE15459), each one-standard-deviation increase in TGFBR1 expression was associated with higher risk of death: unadjusted HR 1.27 (95% CI 1.03 to 1.57); adjusted for age, sex and stage HR 1.38 (95% CI 1.10 to 1.74); additionally adjusted for Lauren classification HR 1.42 (95% CI 1.10 to 1.82).
  • In gastric cancer cell lines, TGFBR1 knockdown reduced proliferation and migration, changed EMT-associated protein expression and increased apoptosis.
• The authors' conclusion: The authors concluded that multivariable analyses and independent validation support TGFBR1's prognostic relevance in selected malignancies, particularly gastric cancer, and that further mechanistic and prospective studies remain necessary.
• Limitations the authors state:
  • The analyses were mostly retrospective and based on bulk transcriptomic data. Differences in sample composition, clinical annotation and treatment history may have influenced the findings.
  • Tumor grade and treatment information were not consistently available for the multivariable models.
  • External validation used only one gastric cancer cohort.
  • The immune, genomic, co-expression and enrichment analyses were exploratory.
  • Subgroup analyses were exploratory because no formal interaction tests were done.
  • The laboratory experiments used only gastric cancer cell lines and included no rescue experiments or animal (in vivo) validation.

Topics

Medical terms in this study, explained in our Lexicon: Stomach Cancer, Overall Survival, Mesothelioma, Carcinoma, Squamous Cell Carcinoma, Adenocarcinoma, Apoptosis.

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