The role of TAOK3 in cancer progression and development as a prognostic marker: A pan-cancer analysis study

Our plain-English summary of The role of TAOK3 in cancer progression and development as a prognostic marker: A pan-cancer analysis study, by G. Alasiri, B. Alrfaei, A.M. Alaseem, et al (Saudi Pharmaceutical Journal, 2024).

The study

• Authors: G. Alasiri, B. Alrfaei, A.M. Alaseem, O.A. AlKhamees, J.A. Aldali, A.M. Aljehani, A. Alfahed, M.A. Aziz, G. Almuhaini, M.M. Alshehri
• Journal: Saudi Pharmaceutical Journal
• Published: 2024;32(3):101942
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The protein kinase TAOK3, belongs to the MAP kinase family, is one of three closely related members, namely TAOK1, TAOK2, and TAOK3. We performed a pan-cancer investigation of TAOK3 across different cancer types, including uterine carcinosarcoma, adenocarcinoma of the stomach and pancreas, and endometrial carcinoma of the uterus, to better understand TAOK3's role in cancer. In at least 16 types of cancer, our findings indicate that TAOK3 expression levels differ considerably between normal and tumor tissues. In addition, our study is the first to identify the oncogenic role of TAOK3 locus S331 and S471 in renal clear cell carcinoma, Glioblastoma Multiforme, hepatocellular carcinoma, Lung adenocarcinoma, and Pancreatic adenocarcinoma, indicating their involvement in cancer progression. In addition, our data analysis indicates that copy number variation is the most prevalent form of mutation in the TAOK3 gene, and that there is a negative correlation between TAOK3 mRNA and DNA promoter methylation. Moreover, our analysis suggests that TAOK3 may serve as a prognostic marker for several kinds of cancer, including Colon adenocarcinoma, renal clear cell carcinoma, Lower Grade Glioma, Lung adenocarcinoma, Mesothelioma, and hepatocellular carcinoma. In addition, our research on signature cancer genes has uncovered a positive association between TAOK3 and SMAD2, SMAD4, and RNF168 in most of the malignancies we have examined. TAOK3 is also correlated with the frequency of mutations and microsatellite instability in four types of cancer. Numerous immune-related genes are closely associated with TAOK3 levels in numerous malignancies. TAOK3 expression is positively correlated with immune infiltrates, which include activated CD4 T cells, CD8 T cells, and type 2T helper cells. Our pan-cancer analysis of TAOK3 provides vital insight into its potential role across a variety of cancer types.

© 2024 The Authors.

In plain English

This was a computer analysis of public cancer databases, mainly The Cancer Genome Atlas (TCGA). It looked at one gene, TAOK3, across many cancer types, not at asbestos or any other exposure. Using online tools, the authors compared TAOK3 expression in tumor and normal tissue. They also examined survival, gene changes and immune cells. TAOK3 mRNA was lower in tumors than in normal tissue in several cancers, including breast, colon and lung, and higher in others, including liver and stomach. TAOK3 protein, measured in a separate database, was higher in breast tumors and several others. Across 33 cancer types, higher TAOK3 was linked to better overall survival in kidney clear cell carcinoma. In mesothelioma, higher TAOK3 was linked to lower overall and disease-free survival. The text gives no numbers for these links, which it shows in a figure. TAOK3 gene changes appeared in 212 of 10,953 patient samples (2 %). The authors concluded that TAOK3 may promote or suppress tumors depending on the cancer and is a promising prognostic marker. They said laboratory studies are needed to confirm their findings.

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: Pan-cancer bioinformatics analysis of publicly available databases (TCGA, CPTAC and others) using online web tools
• Who was studied: Tumor and normal tissue data from public cancer databases. The survival analysis covered 33 cancer types, including mesothelioma (MESO). The genetic alteration analysis used 10,953 patient samples from the TCGA pan-cancer atlas.
• Main results:
  • TAOK3 mRNA was lower in tumor than in normal tissue in several cancers. These included invasive breast carcinoma (p less than 0.05) and colon, lung, rectum, thyroid and uterine endometrial cancers (all p less than 0.001).
  • TAOK3 mRNA was higher in tumor than in normal tissue in four cancers, all with p less than 0.001: cholangiocarcinoma, head and neck squamous cell carcinoma, liver hepatocellular carcinoma and stomach adenocarcinoma.
  • In the CPTAC protein database, TAOK3 protein was higher in tumor than in normal tissue in five cancers: breast cancer, pancreatic adenocarcinoma, liver hepatocellular carcinoma, glioblastoma multiforme and kidney renal clear cell carcinoma.
  • Higher TAOK3 expression was related to better overall survival in kidney renal clear cell carcinoma. In mesothelioma, higher TAOK3 levels correlated with lower survival. The text gives no hazard ratios or p-values for these links.
  • In mesothelioma and uveal melanoma, higher TAOK3 expression correlated with lower disease-free survival.
  • TAOK3 alterations were found in 212 of 10,953 patient samples (2 %).
  • Bladder urothelial carcinoma had the highest alteration frequency (4.87 %). Copy number amplification was the main type of change (1.95 %).
  • TAOK3 promoter DNA methylation was negatively correlated with TAOK3 expression in 31 cancer types.
  • SMAD4, SMAD2 and RNF168 correlated positively with TAOK3 in 37 cancer types.
  • Most immune cell types correlated positively with TAOK3, especially neutrophils, endothelial cells and monocytic lineage.
• The authors' conclusion: The authors concluded that TAOK3 has both oncogenic and tumor suppressor roles in different cancers. They described it as a promising prognostic biomarker for numerous cancer types.
• Limitations the authors state:
  • The authors stated that functional studies are needed to confirm their findings.
  • Mutation effects on cancer hallmark genes could only be analyzed in 4 cancer types.

Topics

Medical terms in this study, explained in our Lexicon: Adenocarcinoma, Carcinoma, Lung Adenocarcinoma, Mesothelioma, Microsatellite Instability (MSI-H).

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