Research Paper|Volume 16, Issue 2|pp 1440—1462

Identification and validation of SLCO4C1 as a biological marker in hepatocellular carcinoma based on anoikis classification features

Tianbing Wang¹, Kai Guo¹, Shoushan Yang^2,^3,^4,⁵, Di Zhang⁶, Haodong Cui^2,^3,⁴, Jimin Yin^2,^3,⁴, Shuhui Yuan⁷, Yong Wang¹, Yong Qi⁸, Wenyong Wu^2,^3,⁴

¹Department of General Surgery, Anhui No. 2 Provincial People’s Hospital, Hefei 230000, China
²Anhui No. 2 Provincial People’s Hospital Clinical College of Anhui Medical University, Hefei 230000, China
³Anhui No. 2 Provincial People’s Hospital, Hefei 230000, China
⁴The Fifth Clinical Medical College of Anhui Medical University, Hefei 230000, China
⁵Department of General Surgery, Luan Fourth People’s Hospital, Luan 237000, China
⁶Clinical Genomic Center, Hefei KingMed for Clinical Laboratory, Hefei 230000, China
⁷Anhui Huaheng Biotechnology Co., Ltd., Hefei 230000, China
⁸Department of General Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei 230000, China

* Equal contribution

Received: September 18, 2023Accepted: December 4, 2023Published: January 15, 2024

https://doi.org/10.18632/aging.205438

Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Hepatocellular carcinoma (HCC) exhibits a high degree of invasiveness and is closely associated with rapid disease progression. Multiple lines of evidence indicate a strong correlation between anoikis resistance and tumor progression, invasion, and metastasis. Nevertheless, the classification of anoikis in HCC and the investigation of novel biological target mechanisms in this context continue to pose challenges, requiring further exploration.

Methods: Combined with HCC samples from TCGA, GEO and ICGC databases, cluster analysis was conducted on anoikis genes, revealing novel patterns among different subtypes. Significant gene analysis of different gene subtypes was performed using WCGNA. The anoikis prognostic risk model was established by Lasso-Cox. Go, KEGG, and GSEA were applied to investigate pathway enrichment primarily observed in risk groups. We compared the disparities in immune infiltration, TMB, tumor microenvironment (TME), and drug sensitivity between the two risk groups. RT-qPCR and Western blotting were performed to validate the expression levels of SLCO4C1 in HCC. The biological functions of SLCO4C1 in HCC cells were assessed through various experiments, including CCK8 assay, colony formation assay, invasion migration assay, wound healing assay, and flow cytometry analysis.

Results: HCC was divided into 2 anoikis subtypes, and the subtypeB had a better prognosis. An anoikis prognostic model based on 12 (COPZ2, ACTG2, IFI27, SPP1, EPO, SLCO4C1, RAB26, STC2, RAC3, NQO1, MYCN, HSPA1B) risk genes is important for survival and prognosis. Significant differences were observed in immune cell infiltration, TME, and drug sensitivity analysis between the risk groups. SLCO4C1 was downregulated in HCC. SLCO4C1 downregulation promoted the proliferation, invasion, migration, and apoptosis of HCC cells. The tumor-suppressive role of SLCO4C1 in HCC has been confirmed.

Conclusions: Our study presents a novel anoikis classification method for HCC that reveals the association between anoikis features and HCC. The anoikis feature is a critical biomarker bridging tumor cell death and tumor immunity. In this study, we provided the first evidence of SLCO4C1 functioning as a tumor suppressor in HCC.