A Pan-Cancer Analysis of the Oncogenic Role of Twinfilin Actin Binding Protein 1 in Human Tumors

Our plain-English summary of A Pan-Cancer Analysis of the Oncogenic Role of Twinfilin Actin Binding Protein 1 in Human Tumors, by G. Huo, Y. Wang, J. Chen, et al (Frontiers in Oncology, 2021).

The study

• Authors: G. Huo, Y. Wang, J. Chen, Y. Song, C. Zhang, H. Guo, R. Zuo, F. Zhu, J. Cui, W. Chen, W. Chen, P. Chen
• Journal: Frontiers in Oncology
• Published: 2021;11:692136
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Understanding common and unique mechanisms driving oncogenic processes in human tumors is indispensable to develop efficient therapies. Recent studies have proposed Twinfilin Actin Binding Protein 1 (TWF1) as a putative driver gene in lung cancer, pancreatic cancer and breast cancer, however a systematic pan-cancer analysis has not been carried out.

Methods: Here, we set out to explore the role of TWF1 in 33 tumor types using TCGA (The Cancer Genome Atlas), GEO (Gene Expression Omnibus) dataset, Human Protein Atlas (HPA), and several bioinformatic tools.

Results: As part of our analysis, we have assessed TWF1 expression across tumors. We found that over-expression of TWF1 generally predicted poor OS for patients with tumors with high TWF1 expression, such as mesothelioma, lung adenocarcinoma, cervical cancer and pancreatic adenocarcinoma. We also assessed the mutation burden of TWF1 in cancer and the TWF1-associated survival of cancer patients, compared the phosphorylation of TWF1 between normal and primary tumor tissues and explored putative functional mechanisms in TWF1-mediated oncogenesis.

Conclusions: Our pan-cancer analysis provides a comprehensive overview of the oncogenic roles of TWF1 in multiple human cancers.

Copyright © 2021 Huo, Wang, Chen, Song, Zhang, Guo, Zuo, Zhu, Cui, Chen, Chen and Chen.

In plain English

This study was a computer-based analysis of public cancer databases, mainly The Cancer Genome Atlas (TCGA), of a gene called TWF1 (Twinfilin Actin Binding Protein 1) in 33 tumor types. It did not study asbestos or any other exposure. The authors compared TWF1 RNA and protein expression in tumor and normal tissue. To compare survival, they split patients into high- and low-expression groups at a 50% cutoff. In most tumor types, TWF1 RNA expression was higher in tumors than in normal tissue. It was lower in kidney renal clear cell carcinoma, prostate adenocarcinoma and rectum adenocarcinoma, though kidney clear cell tumors had higher total TWF1 protein. High TWF1 expression was associated with poorer overall survival in mesothelioma (P=0.0016), lung adenocarcinoma (P=0.00014), cervical cancer (P=0.045) and pancreatic adenocarcinoma (P=0.031). The text does not say whether the mesothelioma cases were pleural or peritoneal or give patient numbers or risk estimates for them; the survival figures were not reproduced here. The authors concluded that TWF1 is a potential biomarker for predicting prognosis, including overall survival in mesothelioma. They called for further studies of its function.

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 (computer-based) pan-cancer analysis of public databases (TCGA, GEO, GTEx, CPTAC, Human Protein Atlas) using online tools
• Who was studied: Tumor and normal tissue data for 33 tumor types in TCGA, including mesothelioma (MESO). Patient numbers are given in the text only for lung cancers: TCGA-LUSC (n=501) and TCGA-LUAD (n=515). No dates or locations are given.
• Exposure: No asbestos or other environmental or occupational exposure was studied. The factor examined was TWF1 gene and protein expression, genetic alteration and phosphorylation.
• Main results:
  • In TCGA tumors, high TWF1 expression was associated with poorer overall survival for cervical cancer (CESC, P=0.045), lung adenocarcinoma (LUAD, P=0.00014), mesothelioma (MESO, P=0.0016) and pancreatic adenocarcinoma (PAAD, P=0.031).
  • For disease-free survival, high TWF1 expression was associated with poorer outcome in lung adenocarcinoma (P=0.0087). Low expression was associated with poorer outcome in breast cancer (BRCA, P=0.036).
  • In the tumor-versus-normal gene-expression comparison, TWF1 expression was higher in tumor tissue in the majority of tumor types. It was lower in KIRC, PRAD and READ.
  • In CPTAC protein data, total TWF1 protein was higher in tumor tissue than in normal tissue for ovarian, kidney clear cell (KIRC), uterine endometrial, lung adenocarcinoma and breast cancer (P<0.001).
  • In uterine corpus endometrial carcinoma (UCEC), patients with TWF1 genetic alterations had better disease-free survival (P=0.046). Progression-free survival (P=0.053) and overall survival (P=0.996) were not significantly different.
  • Pathway analysis of TWF1-related genes found 'focal adhesion' and 'vesicle transportation' among the top results.
• The authors' conclusion: The authors concluded that TWF1 is a potential biomarker for predicting the prognosis of tumor patients. They suggested their findings may provide a biomarker for predicting overall survival in mesothelioma patients.
• Limitations the authors state:
  • The authors stated that additional gain- and loss-of-function studies are needed to explore TWF1's function in different cellular contexts.

Topics

Medical terms in this study, explained in our Lexicon: Lung Cancer, Mesothelioma, Lung Adenocarcinoma, Adenocarcinoma, Carcinogenesis.

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