RAD51AP1 as an Immune-Related Prognostic Biomarker and Therapeutic Response Predictor in Hepatocellular Carcinoma

Yongguang Wei; Chenlu Lan; Xiangkun Wang; Xin Zhou; Xiwen Liao; Huasheng Huang; Zhongliu Wei; Tianman Li; Tao Peng; Guangzhi Zhu

doi:10.2147/IJGM.S431206

RAD51AP1 as an Immune-Related Prognostic Biomarker and Therapeutic Response Predictor in Hepatocellular Carcinoma

Int J Gen Med. 2023 Sep 26:16:4377-4392. doi: 10.2147/IJGM.S431206. eCollection 2023.

Authors

Yongguang Wei^#^{1

2

3}, Chenlu Lan^#^{1

2

3}, Xiangkun Wang⁴, Xin Zhou^{1

2

3}, Xiwen Liao^{1

2

3}, Huasheng Huang^{1

2

3}, Zhongliu Wei^{1

2

3}, Tianman Li^{1

2

3}, Tao Peng^{1

2

3}, Guangzhi Zhu^{1

2

3}

Affiliations

¹ Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People's Republic of China.
² Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, 530021, People's Republic of China.
³ Key Laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education, Nanning, 530021, People's Republic of China.
⁴ Departments of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.

^# Contributed equally.

Abstract

Background: RAD51 associated protein 1 (RAD51AP1) is shown to regulate cell proliferation and cancer progression. However, the immune-infiltrating correlation and the therapeutics guidance of RAD51AP1 in hepatocellular carcinoma (HCC) still need further investigation.

Methods: In this study, comprehensive bioinformatic analysis of RAD51AP1 on differential expression, clinicopathologic correlation, prognostic value, and function enrichment were performed in The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO; GSE14520 and GSE76427), and International Cancer Genome Consortium (ICGC) datasets. Besides, the Guangxi cohort containing 50 pairs HCC and adjacent non-cancerous samples from First Affiliated Hospital of Guangxi Medical University was served as validation cohort. Moreover, we explored the predictive value of RAD51AP1 to therapeutics response and its underlying correlation with HCC immunoinfiltration.

Results: RAD51AP1 was significantly overexpressed in HCC tissues and had a high diagnostic value of HCC. The shorter survival time and poorer clinical features were showed when RAD51AP1 upregulated, and then a nomogram featuring RAD51AP1 expression and other clinicopathologic factors was established to predict prognosis. In CIBERSORT analysis, higher T cells follicular helper but lower T cells CD4+ memory resting infiltration levels were exhibited when RAD51AP1 upregulated. The ssGSEA analysis demonstrated that high-RAD51AP1 expression subgroup had higher macrophages, Th2 and Treg cells infiltration levels, but lower type II IFN response function. Furthermore, high-RAD51AP1 expression subgroup exhibited the upregulated expression levels of immune-related checkpoint genes, but lower IPS and TIDE scores which suggested a possibly better immunotherapy response. The drug sensitivity analysis showed the high-expression subgroup may be more susceptible to Bexarotene, Doxorubicin, Gemcitabine and Tipifarnib.

Conclusion: Taken together, RAD51AP1 is a potential diagnostic and prognostic biomarker. It may be related to the immunosuppressive microenvironment and could be an underlying HCC treatment strategy. However, the conclusions still require further validation studies.

Keywords: RAD51AP1; bioinformatics; drug sensitivity; hepatocellular carcinoma; immune filtration; prognostic signature.

Grants and funding

This work was supported by the National Natural Science Foundation of China No. 81902500, the Key Laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education (grant nos. GKE2018-01, GKE2019-11, GKE-ZZ202009 and GKE-ZZ202109), Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis (No. GXCDCKL201902), Key R&D Plan of Qingxiu District, Nanning (NO.2020056), Natural Science Foundation of Guangxi Province of China (grant no. 2020GXNSFAA159127) and Self-funded Scientific Research Project of Health Commission in Guangxi Zhuang Autonomous Region (Z20210977). The Self‑raised Scientific Research Fund of the Health and Family Planning Commission of the Guangxi Zhuang Autonomous Region (grant no. Z-A20230458).