Gain of GAS5 reveals worse prognosis in kidney renal clear cell carcinoma and liver hepatocellular carcinoma from the Cancer Genome Atlas dataset

Transl Cancer Res. 2021 Jan;10(1):223-232. doi: 10.21037/tcr-20-2221.

Abstract

Background: The role of long non-coding RNA growth arrest-specific 5 (GAS5) in cancer development is controversial. The aim of this study was to evaluate the prognostic significance of GAS5 in kidney renal clear cell carcinoma (KIRC) and liver hepatocellular carcinoma (LIHC) from The Cancer Genome Atlas (TCGA) dataset and to explore its potential regulatory mechanism through data mining.

Methods: Expression of GAS5 and its clinical information within 14 kinds of cancers were obtained from TCGA dataset. The correlation between the expression of GAS5 and abhydrolase domain containing 2 (ABHD2) in KIRC and LIHC were analyzed through R2 website. The overall survival (OS) was assessed using the Kaplan-Meier method. Wilcoxon test was conducted to assess the DNA methylation of CpG sites of GAS5 or ABHD2 between normal and tumor sample in both KIRC and LIHC patients.

Results: Results showed GAS5 was significantly upregulated in KIRC and LIHC tissues compared with normal tissues, which was rarely seen in other cancers. High GAS5 expression was associated with poor overall survival (OS) in both KIRC and LIHC. Our study firstly confirmed a negative correlation between GAS5 and ABHD2 protein in both KIRC and LIHC. Methylation analysis showed that high GAS5 expression had lower DNA methylation status while low ABHD2 expression had higher DNA methylation status in both cancers.

Conclusions: Our research revealed that GAS5 was likely to function as an oncogene in both KIRC and LIHC, and negatively correlated with ABHD2. Furthermore, DNA hypomethylation might have an important effect on increased GAS5 transcription and reduced ABHD2 transcription in both cancers.

Keywords: Prognosis; abhydrolase domain containing 2 (ABHD2); growth arrest-specific 5 (GAS5); kidney renal clear cell carcinoma (KIRC); liver hepatocellular carcinoma.