Pan-cancer analysis shows that TRIP13 as a potential prognostic and immunotherapeutic biomarker for multiple cancer types including LIHC and LUAD

Our plain-English summary of Pan-cancer analysis shows that TRIP13 as a potential prognostic and immunotherapeutic biomarker for multiple cancer types including LIHC and LUAD, by C. Li, Z. Zhou, Y. Liu, et al (Medicine, 2025).

The study

• Authors: C. Li, Z. Zhou, Y. Liu, Y. Guo, T. Liu, J. Teng, P. Chen, A. Hu, L. Wu, D. Qiao, Q. Chen, J. Liu
• Journal: Medicine
• Published: 2025;104(22):e42588
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Growing evidence indicates that thyroid hormone receptor interactor 13 (TRIP13) plays an oncogenic role in various malignancies. Pan-cancer analysis was performed to elucidate the prognostic value and oncogenic role of TRIP13, and detect TRIP13 expression levels in diverse cancer types. We found that TRIP13 was overexpressed in multiple tumors. Subsequently, we explored the relationship between TRIP13 expression-associated alterations and clinical prognosis, DNA methylation, immune cell infiltration, immune checkpoints, tumor mutational burden, microsatellite instability, and drug sensitivity. Gene set enrichment analysis was utilized to explore the molecular mechanism of TRIP13. A nomogram was developed to predict the impact of TRIP13 expression on an liver hepatocellular carcinoma prognosis. The miRDB database was used to predict miRNA targets for TRIP13. The results indicated that TRIP13 overexpression was associated with a poor overall survival, disease-specific survival, and progression-free interval in various cancer types. The mutation frequency of TRIP13 was the highest in individuals with lung squamous cell carcinoma. TRIP13 expression levels were negatively associated with immunocyte infiltration, immune scores, tumor mutational burden, microsatellite instability, and DNA methylation in certain cancers, and positively correlated with the expression of at least 5 immune checkpoint-related genes in bladder carcinoma, breast cancer, kidney clear cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, mesothelioma, and thyroid cancer. In addition, we discovered that TRIP13 participated in the cell cycle during Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis for most cancers. The areas under the curve for the 1-, 3-, and 5-year survival rates in the nomogram exceeded 0.6, indicating that the model has good predictive performance, and was validated using samples obtained from liver hepatocellular carcinoma patients. We also found that miR-656-3p tends to bind to TRIP13 mRNA and regulate TRIP13 expression. Additionally, we identified 26 drugs sensitive to tumors with high TRIP13 expression levels from the CTRP and GDSC databases. Finally, the promoting effect of TRIP13 on lung cancer was verified, the results demonstrating TRIP13 could accelerate lung cancer cell proliferation, migration, and invasion. Collectively, our findings suggest that TRIP13 may act as a potential prognostic marker and novel target for cancer therapy.

Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.

In plain English

This study did not examine asbestos or any occupational or environmental exposure. It analyzed public cancer databases, mainly TCGA, covering 33 cancer types, including mesothelioma (labelled MESO, with no site given). It looked at a gene called TRIP13 and added laboratory tests on one lung cancer cell line, A549. The authors reported that TRIP13 levels were higher in tumor tissue than in healthy tissue in most cancers compared. Higher TRIP13 levels were associated with shorter overall survival and disease-specific survival in several cancers, including mesothelioma, liver cancer and lung adenocarcinoma. In mesothelioma, patients in the group with high TRIP13 methylation, a chemical tag on the DNA, had longer overall survival. TRIP13 levels were also positively associated with at least 5 immune checkpoint genes in mesothelioma and six other cancers. For liver cancer, a prediction tool gave areas under the curve above 0.6 for 1-, 3- and 5-year survival. In the cell tests, raising TRIP13 increased cell growth, movement and invasion, and lowering it reduced them. The authors concluded that TRIP13 was a promising prognostic biomarker in several cancers.

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: Bioinformatic (database) pan-cancer analysis, with in vitro experiments in a lung cancer cell line; the journal labels it an observational study
• Who was studied: Publicly available tumor and healthy-tissue data (TCGA, GTEx, CPTAC and other online databases) for 33 cancer types, including mesothelioma (MESO); sample numbers per cancer not stated in the text. Laboratory work used A549 lung cancer cells.
• Exposure: No asbestos or other environmental or occupational exposure was studied; the factor examined was the expression level of the TRIP13 gene (drug-sensitivity data were analyzed in relation to TRIP13 expression)
• Main results:
  • In paired tumor and healthy samples from 17 cancer types, TRIP13 levels were higher in tumor tissue in all except PAAD and THCA (P < .01)
  • Higher TRIP13 expression was associated with shorter overall survival in KIRP, LIHC, ACC, SKCM, mesothelioma (MESO), LUAD, KIRC and LGG
  • TRIP13 expression was inversely correlated with disease-specific survival in ACC, KIRC, KIRP, LGG, MESO, LIHC, SKCM and LUAD
  • In ROC analysis, TRIP13 distinguished tumor from healthy tissue with AUC above 0.8 in 15 cancer types, e.g. LIHC AUC = 0.982 and LUAD AUC = 0.909 (mesothelioma not listed)
  • Amplification was the most common TRIP13 alteration (14.37% of alterations), and alteration frequency was highest in LUSC
  • Patients in the high TRIP13 methylation group with KIRC, LGG and MESO had longer overall survival
  • TRIP13 expression was positively associated with at least 5 immune checkpoint genes in BLCA, BRCA, KIRC, LIHC, LUAD, MESO and THCA
  • For liver hepatocellular carcinoma (LIHC), the nomogram's AUCs for 1-, 3- and 5-year survival were above 0.6, and the low-risk group had significantly higher survival (P < .001)
  • hsa-miR-656-3p was down-regulated in LIHC (P = .0006), opposite to TRIP13's raised expression
  • 26 drugs overlapped between the CTRP and GDSC predictions (the text calls them genes); sensitivity to 9 named drugs was related to TRIP13 expression
  • In A549 lung cancer cells, TRIP13 overexpression increased invasion and siRNA knockdown suppressed it; proliferation and migration changed in the same directions
• The authors' conclusion: The authors concluded that TRIP13 was a promising prognostic biomarker and a potential predictor of sensitivity to immunotherapy in several malignant tumors and in LIHC
• Limitations the authors state:
  • The authors stated it still needs to be verified whether the suppressive effect of hsa-miR-656-3p on liver cancer results from suppression of TRIP13

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Prognosis, Tumor Mutational Burden (TMB), Microsatellite Instability (MSI-H), Carcinoma, Overall Survival, Squamous Cell Carcinoma, Lung Adenocarcinoma.

Related studies

• Analysis of a pan-cancer panel reveals the amino acid metabolism-related gene MTHFD1 as a potential prognostic and immunotherapeutic biomarker — S. Gong, J. Yang, et al. (2025)
• SORORIN and PLK1 as potential therapeutic targets in malignant pleural mesothelioma — T. Kato, D. Lee, et al. (2016)
• COL1A1 Is a Potential Prognostic Biomarker and Correlated with Immune Infiltration in Mesothelioma — C. Zhang, S. Liu, et al. (2021)
• Pan-cancer analysis of TMED2: unraveling potential immune characteristics and prognostic value in cancer therapy — Z. Wang, C. Sun, et al. (2025)
• NF2 is a candidate diagnosis, prognostic, and immunotherapeutic biomarker: a systematic pan-cancer analysis — H. Zhang, J. Liu (2024)
• Meta-analysis of several gene lists for distinct types of cancer: a simple way to reveal common prognostic markers — X. Yang, X. Sun (2007)

Browse more research in Medicine, or return to medical research.