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DNA methylation of Hugl-2 is a prognostic biomarker in kidney renal clear cell carcinoma.

ABSTRACT: It has been reported that loss of Hugl-2 contributes to tumour formation and progression in vitro and in vivo. However, whether Hugl-2 levels decrease during kidney renal clear cell carcinoma (KIRC) and the mechanism involved remain unknown. This study aimed to investigate whether DNA methylation of Hugl-2 reduces its expression, leading to the progression and poor prognosis of KIRC. Hugl-2 methylation and mRNA expression and KIRC clinicopathological data were extracted from The Cancer Genome Atlas (TCGA), and relationships among these factors were analyzed using UALCAN, MethHC, Wanderer and LinkedOmics web tools. We found that Hugl-2 mRNA and protein levels were reduced in KIRC tissues. Moreover, Hugl-2 mRNA levels were related to tumour grade and overall survival, and Hugl-2 methylation was increased in KIRC. According to the results of methylation-specific PCR, KIRC cells had higher Hugl-2 DNA methylation levels than HKC cells. Moreover, Hugl-2 DNA methylation correlated negatively with Hugl-2 mRNA and was also related to the pathology and T stage of KIRC patients. KIRC patients with high Hugl-2 DNA methylation also had shorter overall survival. Additionally, methylation of cg08827674, a Hugl-2 probe, was related to pathologic stage, T stage, neoplasm histologic grade, serum calcium level without laterality, M stage, N stage, and ethnicity. Furthermore, treatment with the DNA methylation inhibitor decitabine resulted in upregulation of Hugl-2 mRNA and protein levels in KIRC cell lines. These results indicate that Hugl-2 DNA methylation may be both a prognostic marker and a therapeutic target in KIRC.

SUBMITTER: Miao Y

PROVIDER: S-EPMC7821335 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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DNA methylation of Hugl-2 is a prognostic biomarker in kidney renal clear cell carcinoma.

Miao Yi Y Cao Fang F Li Pingping P Liu Peijun P

Clinical and experimental pharmacology & physiology 20200920 1

It has been reported that loss of Hugl-2 contributes to tumour formation and progression in vitro and in vivo. However, whether Hugl-2 levels decrease during kidney renal clear cell carcinoma (KIRC) and the mechanism involved remain unknown. This study aimed to investigate whether DNA methylation of Hugl-2 reduces its expression, leading to the progression and poor prognosis of KIRC. Hugl-2 methylation and mRNA expression and KIRC clinicopathological data were extracted from The Cancer Genome At ...[more]

PMID: 32754907

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Project description:Background: Kidney renal clear cell carcinoma (KIRC) is a representative histologic subtype of renal cell carcinoma (RCC). RCC exhibits a strong immunogenicity with a prominent dysfunctional immune infiltration. Complement C1q C chain (C1QC) is a polypeptide in serum complement system and is involved in tumorigenesis and the modulation of tumor microenvironment (TME). However, researches have not explored the effect of C1QC expression on prognosis and tumor immunity of KIRC. Methods: The difference in a wide variety of tumor tissues and normal tissues in terms of the C1QC expression was detected using TIMER and TCGA portal databases, and further validation of protein expression of C1QC was conducted via Human Protein Atlas. Then, the associations of C1QC expression with clinicopathological data and other genes were studied with the use of UALCAN database. Subsequently, the association of C1QC expression with prognosis was predicted by searching the Kaplan-Meier plotter database. A protein-protein interaction (PPI) network with the Metascape database was built using STRING software, such that the mechanism underlying the C1QC function can be studied in depth. The TISCH database assisted in the evaluation of C1QC expression in different cell types in KIRC at the single-cell level. Moreover, the association of C1QC and the infiltration level of tumor immune cell was assessed using TIMER platform. The TISIDB website was selected to deeply investigate the Spearman correlation between C1QC and immune-modulator expression. Lastly, how C1QC affected the cell proliferation, migration, and invasion in vitro was assessed using knockdown strategies. Results: KIRC tissues had notably upregulated C1QC level in comparison with adjacent normal tissues, with showed a positive relevance to clinicopathological features including tumor stage, grade, and nodal metastasis, and a negative relevance to clinical prognosis in KIRC. C1QC knockdown inhibited KIRC cell proliferation, migration, and invasion, as indicated by the results of the in vitro experiment. Furthermore, functional and pathway enrichment analysis demonstrated that C1QC was involved in immune system-related biological processes. According to single-cell RNA analysis, C1QC exhibited a specific upregulation in macrophages cluster. Additionally, there was an obvious association of C1QC and a wide variety of tumor-infiltrating immune cells in KIRC. Also, high C1QC expression presented inconsistent prognosis in different enriched immune cells subgroups in KIRC. Immune factors might contribute to C1QC function in KIRC. Conclusion: C1QC is qualified to predict KIRC prognosis and immune infiltration biologically. Targeting C1QC may bring new hope for the treatment of KIRC.

Dataset Information

DNA methylation of Hugl-2 is a prognostic biomarker in kidney renal clear cell carcinoma.

Publications

DNA methylation of Hugl-2 is a prognostic biomarker in kidney renal clear cell carcinoma.

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