CDK12 is a potential biomarker for diagnosis, prognosis and immunomodulation in pan-cancer

Our plain-English summary of CDK12 is a potential biomarker for diagnosis, prognosis and immunomodulation in pan-cancer, by K.Q. Lu, Z.L. Li, Q. Zhang, et al (Scientific Reports, 2024).

The study

• Authors: K.Q. Lu, Z.L. Li, Q. Zhang, Q. Yin, Y.L. Zhang, W.J. Ni, L.Z. Jiang, W. He, B. Wang
• Journal: Scientific Reports
• Published: 2024;14(1):6574
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Cell cycle-dependent protein kinase 12 (CDK12) plays a key role in a variety of carcinogenesis processes and represents a promising therapeutic target for cancer treatment. However, to date, there have been no systematic studies addressing its diagnostic, prognostic and immunological value across cancers. Here, we found that CDK12 was significantly upregulated in various types of cancers, and it expression increased with progression in ten cancer types, including breast cancer, cholangiocarcinoma and colon adenocarcinoma. Moreover, the ROC curves indicated that CDK12 showed diagnostic value in eight cancer types. High CDK12 expression was associated with poor prognosis in eight types of cancer, including low-grade glioma, mesothelioma, melanoma and pancreatic cancer. Furthermore, we conducted immunoassays to explore the exact mechanisms underlying CDK12-induced carcinogenesis, which revealed that increased expression of CDK12 allowed tumours to evade immune surveillance and upregulate immune checkpoint genes. Additionally, mutational studies have shown that amplification and missense mutations are the predominant mutational events affecting CDK12 across cancers. These findings establish CDK12 as a significant biological indicator of cancer diagnosis, prognosis, and immunotherapeutic targeting. Early surveillance and employment of CDK12 inhibitors, along with concomitant immunotherapy interventions, may enhance the clinical outcomes of cancer patients.

© 2024. The Author(s).

In plain English

This was a computer-based (bioinformatics) analysis of public databases, not a study of asbestos; the article does not mention asbestos. The authors examined the expression levels of a gene called CDK12 across 33 cancer types from the TCGA database, one of which was mesothelioma. They compared these with normal tissue data from GTEx, using 26,801 samples in total. CDK12 expression was higher than in normal samples in 20 cancer types and lower in five. CDK12 level was significantly linked to overall survival in nine cancers, including mesothelioma, where it was reported as a high-risk factor. Higher expression was associated with poorer disease-specific survival in low-grade glioma, mesothelioma, skin melanoma and pancreatic cancer. The text gives no hazard ratio for mesothelioma. CDK12 levels also correlated with estimated immune cell levels in tumours and with immune checkpoint genes. CDK12 mutations were found in 5% of 10,967 samples. The authors concluded that CDK12 may serve as a marker for early cancer diagnosis and for predicting prognosis. They noted that their data lacked experimental and clinical validation.

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 analysis of public gene-expression, survival and mutation databases (pan-cancer analysis); no laboratory or clinical experiments
• Who was studied: Database samples: normal tissues from GTEx (31 tissue types) and tumour and normal samples from TCGA covering 33 cancer types, including mesothelioma (MESO), 26,801 samples in all. Also 1409 cancer cell line samples from CCLE and 10,967 samples from 30 cancers in cBioPortal. No locations or years of sample collection are given.
• Exposure: No asbestos or other occupational exposure was studied. The factor examined was CDK12 gene expression, along with its mutations and methylation.
• Main results:
  • Compared with normal samples, CDK12 expression was higher in 20 cancer types and lower in five (ACC, OV, THCA, UCEC and UCS)
  • In 10 cancer types, CDK12 expression was significantly higher at advanced stages than at earlier stages
  • In the ROC analysis, the highest reported diagnostic accuracy (AUC) was 0.942, for 5-year survival time in glioblastoma (GBM)
  • CDK12 expression was significantly correlated with overall survival in nine cancers, including mesothelioma (MESO)
  • Among those nine cancers, CDK12 was a low-risk factor in KIRC and READ and a high-risk factor in the others. The highest hazard ratio was 9.442, in kidney chromophobe (KICH).
  • For disease-specific survival, high CDK12 expression was associated with poor prognosis in LGG, MESO, SKCM and PAAD, and the opposite was found in ESCA, KIRC and READ
  • In most cancers, CDK12 expression was significantly negatively correlated with stroma, immune and microenvironment scores
  • Overall, most immune checkpoint and immune stimulatory molecules showed a positive correlation with CDK12 expression
  • The CDK12 somatic mutation frequency was 5% across 10,967 samples. Oesophageal cancer had the highest frequency, at 12.94%.
• The authors' conclusion: The authors concluded that CDK12 may serve as a biological marker for early cancer diagnosis and for predicting patient prognosis
• Limitations the authors state:
  • The data come entirely from public databases and lack experimental and clinical validation
  • The mechanisms behind the link between CDK12 and the tumour immune microenvironment remain largely unexplored

Topics

The National Library of Medicine indexes this study under subjects our site covers: Colon cancer.

Medical terms in this study, explained in our Lexicon: Biomarker, Prognosis, Carcinogenesis, Adenocarcinoma, Mesothelioma, Immunotherapy.

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