Molecular Associations and Clinical Significance of RAPs in Hepatocellular Carcinoma.

Sarita Kumari,Anita Chopra,Jay Singh,Shyam S Chauhan,Rajni Yadav,Lokesh K Kadian,Mohit Arora

doi:10.3389/fmolb.2021.677979

Sarita Kumari, Anita Chopra + Show 5 more

Open Access

https://doi.org/10.3389/fmolb.2021.677979

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Abstract

Hepatocellular carcinoma (HCC) is an aggressive gastrointestinal malignancy with a high rate of mortality. Multiple studies have individually recognized members of RAP gene family as critical regulators of tumor progression in several cancers, including hepatocellular carcinoma. These studies suffer numerous limitations including a small sample size and lack of analysis of various clinicopathological and molecular features. In the current study, we utilized authoritative multi-omics databases to determine the association of RAP gene family expression and detailed molecular and clinicopathological features in hepatocellular carcinoma (HCC). All five RAP genes were observed to harbor dysregulated expression in HCC compared to normal liver tissues. RAP2A exhibited strongest ability to differentiate tumors from the normal tissues. RAP2A expression was associated with progressive tumor grade, TP53 and CTNNB1 mutation status. Additionally, RAP2A expression was associated with the alteration of its copy numbers and DNA methylation. RAP2A also emerged as an independent marker for patient prognosis. Further, pathway analysis revealed that RAP2A expression is correlated with tumor-infiltrating immune cell composition and oncogenic molecular pathways, such as cell cycle and cellular metabolism.

Highlights

Hepatocellular carcinoma (HCC) is the sixth leading cancer in incidence and the fourth most common cause of cancer mortality in the world (Bray et al, 2018)
RAP2C expression was higher in tumors compared to adjacent normal tissues, but both these groups exhibited lower expression of RAP2C compared to normal tissues from GTEx (Figure 1I)
Tumor adjacent normal tissues exhibited higher expression of RAP1A and RAP2B, while no difference was observed for RAP1B and RAP2A

Summary

Introduction

Hepatocellular carcinoma (HCC) is the sixth leading cancer in incidence and the fourth most common cause of cancer mortality in the world (Bray et al, 2018). It is the most common type of primary liver cancer that usually arises on the background of chronic liver disease, hepatitis B or C virus infection, or nonalcoholic steatohepatitis (Bruix et al, 2011; Villanueva, 2019). The recent emergence of high throughput sequencing data by multiple studies has enabled researchers to describe molecular features of HCC in detail and has provided several potential biomarkers for the prediction of patient prognosis (Wheeler and Roberts, 2017)

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