Integrative pan-cancer analysis of MEK1 aberrations and the potential clinical implications

Our plain-English summary of Integrative pan-cancer analysis of MEK1 aberrations and the potential clinical implications, by Z. Zhou, B. Peng, J. Li, et al (Scientific Reports, 2021).

The study

• Authors: Z. Zhou, B. Peng, J. Li, K. Gao, Y. Cai, Z. Xu, Y. Yan
• Journal: Scientific Reports
• Published: 2021;11(1):18366
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Alterations of mitogen-activated protein kinase kinase 1 (MEK1) are commonly associated with tumorigenesis, and MEK1 is thought to be a suitable targeted therapy for various cancers. However, abnormal MEK1 alterations and their relevant clinical implications are unknown. Our research comprehensively analyzed the MEK1 alteration spectrum and provided novel insight for targeted therapies. There were 7694 samples covering 32 types of cancer from The Cancer Genome Atlas (TCGA) database. They were used to conduct an integrative analysis of MEK1 expression, alterations, functional impacts and clinical significance. There was a dramatic difference in the alteration frequency and distribution and clinical implications in 32 types of cancer from the TCGA. Skin cutaneous melanoma (SKCM) has the most alterations and has therapeutic targets located in the protein kinase domain, and the growing expression of SKCM is positively related to patient prognosis. MEK1 expression in lung adenocarcinoma (LUAD), kidney renal papillary cell carcinoma (KIRP), esophageal carcinoma (ESCA) and liver hepatocellular carcinoma (LIHC) is decreased, which is associated with better prognosis, while MEK1 expression in thymoma (THYM), stomach adenocarcinoma (STAD), kidney renal clear cell carcinoma (KIRC), testicular germ cell tumors (TGCTs) and head and neck squamous cell carcinoma (HNSC) is increased, which is associated with better prognosis. Mesothelioma (MESO) has the second highest alterations but has no therapy targets. This study provided a great and detailed interpretation of MEK1 expression, alterations and clinical implications in 32 types of cancer and reminded us to fill the gap in MEK1 research from a new perspective.

© 2021. The Author(s).

In plain English

This was a computer-based analysis of public cancer databases, not a study of asbestos exposure. Asbestos is not mentioned. The authors used The Cancer Genome Atlas (TCGA) and related databases to examine the MEK1 gene across 32 cancer types, including mesothelioma. They looked at how strongly the gene was expressed, how often it was mutated or changed in copy number, and whether its expression was linked to survival. The article describes 7694 samples. Its mutation analysis reports 108 MEK1 mutations among 7867 patients (1.4%), with the highest frequency in skin cutaneous melanoma (6.7%). Mesothelioma had the highest frequency of MEK1 copy number changes (3.5%), all of them amplifications. The authors reported that mesothelioma had no therapy targets. Their comparison of mesothelioma with normal tissue was invalid because of too few samples, and no survival result for mesothelioma is reported. High MEK1 expression went with worse or better overall survival depending on the cancer type. The authors concluded that some cancers with high expression or target sites can be treated with targeted drugs. Parts of the article contradict each other.

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 (database) analysis of genetic, expression and survival data across many cancer types
• Who was studied: Tumor samples covering 32 cancer types from The Cancer Genome Atlas (TCGA). The article gives 7694 samples in its opening summary and 7867 patients in its mutation analysis. Normal-tissue data came from GTEx.
• Exposure: No asbestos or other environmental or occupational exposure was studied. The study examined MEK1 gene expression, mutations and copy number variants.
• Main results:
  • The overall MEK1 mutation frequency was 1.4% (108 of 7867 patients).
  • Skin cutaneous melanoma (SKCM) had the highest MEK1 mutation frequency, 6.7%, more than twice that of cholangiocarcinoma (CHOL, 2.8%).
  • The P124S/L mutation, the most frequent mutation site, occurred almost only in SKCM.
  • Mesothelioma (MESO) had the highest MEK1 copy number variant frequency (3.5%), followed by kidney chromophobe (KICH, 1.5%) and sarcoma (SARC, 1.2%).
  • Mesothelioma had the second highest MEK1 alterations, consisting only of amplification, but had no therapy targets.
  • The tumor-versus-normal expression comparison was invalid for three cancer types, including mesothelioma, because of the limited number of samples.
  • MEK1 mRNA and protein expression were positively correlated across cancers (r = 0.6703, p less than 0.0001).
  • High MEK1 expression was a risk factor for overall survival in 'AUAD' (as printed) and liver hepatocellular carcinoma (LIHC). It was a protective factor in melanoma, thymoma (THYM), stomach adenocarcinoma (STAD), kidney renal papillary cell carcinoma (KIRP) and esophageal carcinoma (ESCA). No hazard ratios are given in the text.
  • High MEK1 expression was positively correlated with progression-free survival in kidney renal clear cell carcinoma (KIRC), STAD, testicular germ cell tumors (TGCT) and head and neck squamous cell carcinoma (HNSC).
• The authors' conclusion: The authors concluded that some MEK1 alterations are related to tumor development, others to targeted therapy, and that some cancers with high expression or target sites can be treated with targeted drugs.
• Limitations the authors state:
  • The authors stated that the mutation frequency results may be limited by the samples and their range.

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenesis, Targeted Therapy, Prognosis, Lung Adenocarcinoma, Carcinoma, Adenocarcinoma, Germ Cell Tumor, Squamous Cell Carcinoma.

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