肝细胞癌中自噬相关生物标志物及其与免疫浸润的关系

Autophagy-related biomarkers in hepatocellular carcinoma and their relationship with immune infiltration.

作者信息

Li Tingting, Zhang Lin

机构信息

Clinical Laboratory Department, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

Discov Oncol. 2024 Jul 23;15(1):299. doi: 10.1007/s12672-024-01167-x.

DOI:10.1007/s12672-024-01167-x

PMID:39042294

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11266335/

Abstract

BACKGROUND

Autophagy regulation plays vital roles in many cancers. We aimed to investigate the expression, prognostic value, and immune infiltration of autophagy-related genes in hepatocellular carcinoma (HCC) by bioinformatics analysis.

METHOD

Human autophagy-related differentially expressed genes (DEGs) between adjacent and HCC tissues were identified. We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We also evaluated immune infiltration and the response to tumor-sensitive drugs. Finally, we verified the expression of these proteins in clinical samples by immunohistochemistry (IHC), RNA isolation and real-time reverse transcription polymerase chain reaction (RT‒PCR).

RESULTS

A total of 57 autophagy-related DEGs were identified. The HUB genes (BIRC5, CDKN2A, SPP1, and IGF1) were related to the diagnosis and prognosis of HCC. The HUB genes were significantly enriched in immune-related pathways. Furthermore, correlation analysis revealed that HUB gene expression was associated with immune infiltration. We identified 35 tumor-sensitive drugs targeting the HUB genes. Finally, by IHC, we discovered that the protein of CDKN2A, BIRC5, and SPP1 were upregulated in HCC tissues, while IGF1 was downregulated in HCC tissues compared with the levels in paracarcinoma tissues; by RT‒PCR, we discovered that the mRNA of CDKN2A, BIRC5, and SPP1 were upregulated in HCC tissues, while the mRNA of IGF1 was downregulated in HCC tissues compared with the levels in paracarcinoma tissues.

CONCLUSION

We screened and validated four autophagy-related genes associated with immune infiltration and prognosis in patients with HCC.

摘要

背景

自噬调节在多种癌症中起着至关重要的作用。我们旨在通过生物信息学分析研究自噬相关基因在肝细胞癌（HCC）中的表达、预后价值及免疫浸润情况。

方法

鉴定相邻组织与HCC组织之间的人类自噬相关差异表达基因（DEG）。我们进行了基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析。我们还评估了免疫浸润及对肿瘤敏感药物的反应。最后，我们通过免疫组织化学（IHC）、RNA分离和实时逆转录聚合酶链反应（RT-PCR）验证了这些蛋白在临床样本中的表达。

结果

共鉴定出57个自噬相关DEG。枢纽基因（BIRC5、CDKN2A、SPP1和IGF1）与HCC的诊断和预后相关。枢纽基因在免疫相关途径中显著富集。此外，相关性分析显示枢纽基因表达与免疫浸润相关。我们鉴定出35种靶向枢纽基因的肿瘤敏感药物。最后，通过IHC发现，与癌旁组织相比，CDKN2A、BIRC5和SPP1蛋白在HCC组织中上调，而IGF1在HCC组织中下调；通过RT-PCR发现，与癌旁组织相比，CDKN2A、BIRC5和SPP1的mRNA在HCC组织中上调，而IGF1的mRNA在HCC组织中下调。