Regulator of G Protein Signaling 20 Correlates with Long Intergenic Non-Coding RNA (lincRNAs) Harboring Oncogenic Potential and Is Markedly Upregulated in Hepatocellular Carcinoma

Our plain-English summary of Regulator of G Protein Signaling 20 Correlates with Long Intergenic Non-Coding RNA (lincRNAs) Harboring Oncogenic Potential and Is Markedly Upregulated in Hepatocellular Carcinoma, by Y. Wang, M.F. Setiawan, H. Liu, et al (Biology, 2022).

The study

• Authors: Y. Wang, M.F. Setiawan, H. Liu, T.C. Dakal, H. Liu, F. Ge, O. Rudan, P. Chen, C. Zhao, M.A. Gonzalez-Carmona, M.T. Kornek, C.P. Strassburg, M. Schmid, J. Maciaczyk, A. Sharma, I.G.H. Schmidt-Wolf
• Journal: Biology
• Published: 2022;11(8)
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Hepatocellular carcinoma (HCC) is at the forefront of the global cancer burden, and biomarkers for HCC are constantly being sought. Interestingly, RGS (Regulators of G protein signaling) proteins, which negatively regulate GPCR signaling, have been associated with various cancers, with some members of the RGS family being associated with liver cancer as well. Considering this, we investigated the role of RGS20 as a potential prognostic marker in 28 different cancer types with special emphasis on HCC. By using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data, our analysis revealed that (a) RGS20 was strongly upregulated in tumor tissue compared with adjacent normal tissue of HCC patients; (b) RGS20 was strongly associated with some important clinical parameters such as alpha-fetoprotein and tumor grade in the HCC patients; (c) besides HCC (p < 0.001), RGS20 was found to be an important factor for survival in four other cancers (clear renal cell carcinoma: p < 0.001, lung adenocarcinoma: p = 0.004, mesothelioma: p = 0.039, ovarian serous cystadenocarcinoma: p = 0.048); (d) RGS20 was found to be significantly associated with some tumor-related signaling pathways and long intergenic non-coding RNAs (lincRNAs: LINC00511, PVT1, MIR4435-2HG, BCYRN1, and MAPKAPK5-AS1) that exhibit oncogenic potential. Taken together, we showed that RGS20 correlates with a few HCC-associated lincRNAs harboring oncogenic potential and is markedly upregulated in HCC patients. Our analysis further supports the putative function of RGS proteins, particularly RGS20, in cancer.

In plain English

This study did not examine asbestos exposure. It analyzed publicly available gene-activity data, mainly about liver cancer (hepatocellular carcinoma, HCC), and included mesothelioma as one of 28 cancer types. The authors looked at a gene called RGS20 using data from The Cancer Genome Atlas (TCGA). They checked the HCC results in a second database (GEO dataset GSE76427). In TCGA, RGS20 activity was higher in HCC tumor samples than in normal samples. HCC patients with higher RGS20 activity had worse survival (p = 0.005). Higher RGS20 was linked to higher alpha-fetoprotein levels and higher tumor grade. Across the 28 cancer types, only five showed a survival difference between patients with high and low RGS20 activity. In mesothelioma (79 samples; the article does not say whether pleural or peritoneal), survival was poorer in the high-RGS20 group (p = 0.039). RGS20 activity also correlated with five long non-coding RNAs. The authors concluded that RGS20 is an attractive candidate for predicting survival in HCC patients, and said further experimental and clinical studies are needed to validate the findings.

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: Bioinformatic analysis of publicly available gene expression and clinical data from the TCGA and GEO databases
• Who was studied: TCGA liver cancer dataset: 374 tumor and 50 normal samples, of which 371 primary HCC samples were analyzed. The GEO dataset GSE76427 (115 tumor, 52 normal samples) was used for validation. TCGA samples from 28 cancer types were also analyzed, including mesothelioma (79 samples).
• Exposure: No asbestos or other environmental exposure was studied. The variable studied was RGS20 gene expression, with patients split into high and low groups at the median for each cancer.
• Main results:
  • In TCGA HCC data (371 tumor, 50 normal; plus 50 paired samples), RGS20 expression was higher in tumor samples than in normal samples.
  • HCC patients in TCGA with higher RGS20 expression had worse prognosis (p = 0.005).
  • In HCC patients, RGS20 expression was associated with alpha-fetoprotein (AFP) and tumor grade. In logistic regression, the odds ratio for grade (G3 + G4 vs. G1 + G2) was 2.358 (1.245–4.539) and for AFP (400 or more vs. less than 400) was 2.360 (1.048–5.619).
  • In the GEO validation dataset, RGS20 expression differed between HCC tumor and normal samples (p = 0.023), and the high-RGS20 group had lower survival.
  • Of 28 cancer types, five showed a survival difference between high and low RGS20 groups: KIRC (p less than 0.001), LIHC (p less than 0.001), LUAD (p = 0.004), mesothelioma (MESO, p = 0.039) and OV (p = 0.048). Survival was poorer in the high-RGS20 group for KIRC, LIHC, LUAD and MESO, and in the low-RGS20 group for OV.
  • In HCC, univariate Cox regression gave a hazard ratio for RGS20 (continuous) of 77.931 (5.954–1019.956), p less than 0.001. Multivariable Cox regression found age, stage and RGS20 to be independent factors associated with survival.
  • In HCC, RGS20 expression correlated with five lincRNAs: LINC00511, PVT1, MIR4435-2HG, BCYRN1 and MAPKAPK5-AS1.
• The authors' conclusion: The authors concluded that RGS20 is an attractive candidate for predicting the survival prognosis of HCC patients, and that it correlates with lincRNAs with oncogenic potential and is markedly upregulated in HCC.
• Limitations the authors state:
  • The authors stated that further experimental and clinical studies are required to validate their findings.

Topics

Medical terms in this study, explained in our Lexicon: Carcinoma, Biomarker, Alpha-fetoprotein (AFP), Lung Adenocarcinoma, Mesothelioma.

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