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TSPAN1 – Prostate Cancer

Multiple independent studies have investigated the prognostic value of TSPAN1 in prostate cancer. In one study, transcript-level analysis using The Cancer Genome Atlas (TCGA) cohort (n = 497 PMID:33455017) and an independent prostatectomy cohort (n = 175 PMID:33455017) demonstrated that TSPAN1 expression was univariately associated with biochemical recurrence. However, multivariate analysis did not retain TSPAN1 as an independent prognostic marker, suggesting that its expression may be confounded by factors such as high Gleason scores.

A subsequent study integrated TSPAN1 with other cancer‐associated fibroblast (CAF)‐related genes to construct molecular subtypes and a prognostic index in a cohort of 430 patients (PMID:37270661). Although this approach highlighted TSPAN1 as part of a gene panel that stratified biochemical recurrence risk, the lack of individual variant or mutational evidence further limits its genetic association with prostate cancer.

In contrast to the correlative genetic evidence, functional studies in other cancer types offer insights into the oncogenic properties of TSPAN1. For example, in cholangiocarcinoma, TSPAN1 promotes epithelial‑to‑mesenchymal transition (EMT) via the PI3K/AKT pathway (PMID:30514341). Similarly, investigations in pancreatic cancer have demonstrated that TSPAN1 upregulation enhances proliferation, migration, invasion, and autophagy regulation through both transcriptional and post‑translational mechanisms (PMID:32368389; PMID:32972302). Although these functional assays robustly support the role of TSPAN1 in cancer biology, direct experimental validation in the context of prostate cancer remains limited.

Overall, the genetic evidence linking TSPAN1 to prostate cancer is based primarily on transcriptomic correlations without confirmation of pathogenic coding variants. The absence of clearly defined deleterious mutations, combined with inconsistent multivariate prognostic significance, places the gene‑disease association at a limited level. Nonetheless, the broader oncogenic functions of TSPAN1, as demonstrated in functional studies, underscore its potential as a biomarker for cancer progression.

Key take‑home sentence: TSPAN1 shows promise as a candidate prognostic marker in prostate cancer; however, additional targeted studies are required to validate its clinical utility and decipher its mechanistic role in this disease.

References

  • APMIS • 2021 • Prognostic role of TSPAN1, KIAA1324 and ESRP1 in prostate cancer PMID:33455017
  • Scientific Reports • 2023 • Establishment of cancer‑associated fibroblasts‑related subtypes and prognostic index for prostate cancer through single‑cell and bulk RNA transcriptome PMID:37270661
  • Journal of Experimental & Clinical Cancer Research : CR • 2018 • Tetraspanin 1 promotes epithelial‑to‑mesenchymal transition and metastasis of cholangiocarcinoma via PI3K/AKT signaling PMID:30514341
  • American Journal of Cancer Research • 2020 • miR‑216a‑mediated upregulation of TSPAN1 contributes to pancreatic cancer progression via transcriptional regulation of ITGA2 PMID:32368389
  • Autophagy • 2021 • TSPAN1 promotes autophagy flux and mediates cooperation between WNT‑CTNNB1 signaling and autophagy via the MIR454‑FAM83A‑TSPAN1 axis in pancreatic cancer PMID:32972302

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Two independent multi‑patient studies (n = 497 PMID:33455017 and n = 430 PMID:37270661) provided correlative transcript‑level associations in prostate cancer; however, the failure to retain independent prognostic significance in multivariate analyses limits the overall strength of the gene‑disease association.

Genetic Evidence

Limited

Evidence is limited to transcriptomic profiling without the identification of deleterious coding variants or established pathogenic mutations in TSPAN1 for prostate cancer.

Functional Evidence

Limited

Functional studies in cholangiocarcinoma and pancreatic cancer support oncogenic roles of TSPAN1 via pathways such as PI3K/AKT and autophagy regulation (PMID:30514341; PMID:32368389; PMID:32972302); however, direct functional validation in prostate cancer is lacking.