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PTK6: An emerging biomarker for prognosis and immunotherapeutic response in clear cell renal carcinoma (KIRC).

ABSTRACT: Kidney renal clear cell carcinoma (KIRC), one of the most prevalent form of kidney carcinoma, is highly aggressive cancer known for significant immune infiltration and high mortality rates. The absence of sensitivity to traditional therapy has spurred the search for new treatments. Protein Tyrosine Kinase 6 (PTK6) is implicated in promoting cancer growth, spread, and metastasis. Our review of The Cancer Genome Atlas database revealed PTK6 overexpression in KIRC, though its specific role in this cancer type was unclear. We investigated PTK6's cancer-promoting roles in KIRC using the database and confirmed our findings with patient-derived tissues. Our analysis showed that elevated PTK6 expression is linked to worse outcomes and higher levels of immune infiltration. It also correlates positively with neo-antigens (NEO) and DNA ploidy changes in KIRC. This research delves into PTK6's role in KIRC development, suggesting PTK6 as a possible biomarker for prognosis and treatment in KIRC.

SUBMITTER: Lin L

PROVIDER: S-EPMC11002233 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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PTK6: An emerging biomarker for prognosis and immunotherapeutic response in clear cell renal carcinoma (KIRC).

Lin Lizhen L Gong Siming S Deng Chao C Zhang Guanxiong G Wu Jing J

Heliyon 20240329 7

Kidney renal clear cell carcinoma (KIRC), one of the most prevalent form of kidney carcinoma, is highly aggressive cancer known for significant immune infiltration and high mortality rates. The absence of sensitivity to traditional therapy has spurred the search for new treatments. Protein Tyrosine Kinase 6 (PTK6) is implicated in promoting cancer growth, spread, and metastasis. Our review of The Cancer Genome Atlas database revealed PTK6 overexpression in KIRC, though its specific role in this ...[more]

PMID: 38596018

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Project description:As the most common type of renal cell carcinoma (RCC), the renal clear cell carcinoma (ccRCC) is highly malignant and insensitive to chemotherapy or radiotherapy. Although systemic immunotherapies have been successfully applied to ccRCC in recent years, screening for patients who can benefit most from these therapies is still essential and challenging due to immunological heterogeneity of ccRCC patients. To this end, we implemented a series of deep investigation on the expression and clinic data of ccRCC from The Cancer Genome Atlas (TCGA) International Consortium for Cancer Genomics (ICGC). We identified a total of 946 immune-related genes that were differentially expressed. Among them, five independent genes, including SHC1, WNT5A, NRP1, TGFA, and IL4R, were significantly associated with survival and used to construct the immune-related prognostic differential gene signature (IRPDGs). Then the ccRCC patients were categorized into high-risk and low-risk subgroups based on the median risk score of the IRPDGs. IRPDGs subgroups displays distinct genomic and immunological characteristics. Known immunotherapy-related genes show different mutation burden, wherein the mutation rate of VHL was higher than 40% in the two IRPDGs subgroups, and SETD2 and BAP1 mutations differed most between two groups with higher frequency in the high-risk subgroup. Moreover, IRPDGs subgroups had different abundance in tumor-infiltrating immune cells (TIICs) with distinct immunotherapy efficacy. Plasma cells, regulatory cells (Tregs), follicular helper T cells (Tfh), and M0 macrophages were enriched in the high-risk group with a higher tumor immune dysfunction and rejection (TIDE) score. In contrast, the low-risk group had abundant M1 macrophages, mast cell resting and dendritic cell resting infiltrates with lower TIDE score and benefited more from immune checkpoint inhibitors (ICI) treatment. Compared with other biomarkers, such as TIDE and tumor inflammatory signatures (TIS), IRPDGs demonstrated to be a better biomarker for assessing the prognosis of ccRCC and the efficacy of ICI treatment with the promise in screening precise patients for specific immunotherapies.

Project description:BackgroundNecroptosis has been found to be associated with tumorigenesis and tumor progression. However, the prognostic effect of long noncoding RNAs (lncRNAs) associated with necroptosis in clear cell renal cell carcinoma (ccRCC) is still unclear.MethodsPearson correlation analysis was used to identify necroptosis-related genes and lncRNAs obtained from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) dataset. Least absolute shrinkage and selection operator (LASSO) regression and Cox regression analyses were used to identify a novel necroptosis-associated lncRNAs signature that significantly correlated with survival of ccRCC. Next, single sample gene set enrichment analysis (ssGSEA) was employed to assess the extent of infiltration with immune cells. Analyses to predict the half-maximal inhibitory concentration (IC50) of patients in different risk groups were also conducted. Moreover, follow-up data of an immunotherapy cohort were used to test for differences in the immunotherapeutic efficiency between two risk groups. Finally, patients with ccRCC were divided into two groups based on 6 prognostic lncRNAs.ResultsWe developed a signature of necroptosis-related lncRNAs, which was verified as an independent prognostic factor that can predict prognosis up to 7 years. Patients with higher risk scores were shown to have higher immune suppressive cell infiltration levels and expression of immune checkpoint genes, which suggests that these patients were in a state of immunosuppression. Patients in the low-risk group were found to have an increased response to immunotherapy. A prognostic prediction nomogram was conducted to predict long-term survival of patients. Cluster A tumors were considered hot tumors, since they were correlated with higher levels of immune infiltration and were more sensitive to immunotherapy.ConclusionsA comprehensive bioinformatics analysis was conducted, which found that the necroptosis-associated lncRNA signature might be a potent prognostic factor for patients with ccRCC, which could contribute to improved prognosis of these patients.

Dataset Information

PTK6: An emerging biomarker for prognosis and immunotherapeutic response in clear cell renal carcinoma (KIRC).

Publications

PTK6: An emerging biomarker for prognosis and immunotherapeutic response in clear cell renal carcinoma (KIRC).

Similar Datasets

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