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PKMYT1, exacerbating the progression of clear cell renal cell carcinoma, is implied as a biomarker for the diagnosis and prognosis.

ABSTRACT: Clear cell renal cell carcinoma (ccRCC) is one of the most lethal urological malignancies with high tumor heterogeneity, and reliable biomarkers are still needed for its diagnosis and prognosis. WEE family kinases function as key regulators of the G2/M transition, have essential roles in maintaining cellular genomic stability and have the potential to be promising therapeutic targets in various tumors. However, the roles of WEE family kinases in ccRCC remain undetermined. In the present study, we first explored multiple public datasets and found that PKMYT1 was up-regulated in both RCC tumors and cell lines. Expression levels of PKMYT1 were highly associated with pathological stage and grade. Kaplan-Meier curves showed that high PKMYT1 expression was associated with lower overall survival and disease-free survival. Receiver operating characteristic curves revealed that the expression of PKMYT1 could better distinguish ccRCC from normal samples. Functional enrichment analysis demonstrated that cell cycle- related pathways and epithelial to mesenchymal transition (EMT) might be potential mechanisms of PKMYT1 in ccRCC tumorigenesis. Moreover, knockdown of PKMYT1 in vitro attenuated the proliferation, migration and invasion of RCC cell lines, promoted cell apoptosis and prevented the EMT phenotype in vitro. In conclusion, our study demonstrated that PKMYT1 has the potential to act as a diagnostic and prognostic biomarker for RCC patients. Targeting PKMYT1 may be considered as a new potential therapeutic method and direction in RCCs.

SUBMITTER: Chen J

PROVIDER: S-EPMC8751600 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney tumor worldwide. Analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases showed that the immune-related gene (IRG) hematopoietic cell signal transducer (HCST) could provide guidance for the diagnosis, prognosis, and treatment of ccRCC. The RNA-seq data of ccRCC tissues were extracted from two databases: TCGA (https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga) and GEO (https://www.ncbi.nlm.nih.gov/geo/). Corresponding clinical information was downloaded from TCGA. Immune-related gene data were extracted from the IMMPORT website (https://www.immport.org/). Differential analysis with R software (https://www.r-project.org/) was used to obtain a prognosis model of ccRCC IRGs. The differences were combined with the clinical data to assess the usefulness of the HCST as a prognostic biomarker. Based on data obtained from the Oncomine (https://www.oncomine.org/), Human Protein Atlas (https://www.proteinatlas.org/), and PubMed (https://pubmed.ncbi.nlm.nih.gov/) databases, the expression levels of the HCST in ccRCC, clinical-pathological indicators of relevance, and influence on prognosis were analyzed. Regulation of the HCST gene in ccRCC was assessed by gene set enrichment analysis (GSEA). In TCGA/GEO databases, the high HCST expression in tumor tissues was significantly correlated to the TMN stage, tumor grade, invasion depth, and lymphatic metastasis (p < 0.05). The overall survival (OS) of patients with high HCST gene expression was significantly lower than that of patients with low HCST gene expression (p < 0.001). Multivariate Cox regression analysis suggested that the HCST expression level [hazard ratio (HR) = 1.630, 95% confidence interval (CI) = 1.042-2.552], tumor cell grade (HR = 1.829, 95% CI = 1.115-3.001), and distant metastasis (HR = 2.634, 95%, CI = 1.562-4.442) were independent risk factors affecting the OS of ccRCC patients (all, p < 0.05). The GSEA study showed that there was significant enrichment in cell adhesion, tumorigenesis, and immune and inflammatory responses in HCST high expression samples. Hematopoietic cell signal transducer expression was closely associated with the levels of infiltrating immune cells around ccRCC tissues, especially dendritic cells (DCs). In conclusion, the present study suggested that the HCST was interrelated to the clinicopathology and poor prognosis of ccRCC. High HCST expression was also closely correlated with the levels of tumor-infiltrating immune cells, especially DCs.

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PKMYT1, exacerbating the progression of clear cell renal cell carcinoma, is implied as a biomarker for the diagnosis and prognosis.

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