Zhong Xiaohong, Zhang Zhiyong, Gao Rongjing, Ren Shiqi, Li Shifang, Zhang Miao, Fang Jie, Hou Yanjiao
Department of Clinical Laboratory, Qilu Hospital of Shandong University Dezhou Hospital (Dezhou People's Hospital), Dezhou, Shandong, China.
Pneumology Department, Qilu Hospital of Shandong University Dezhou Hospital (Dezhou People's Hospital), Dezhou, Shandong, China.
Front Genet. 2025 Mar 26;16:1524422. doi: 10.3389/fgene.2025.1524422. eCollection 2025.
Chromosome 8 open reading frame 76 (C8orf76) is a nuclear protein-encoding gene, has received limited attention in current study. Multi-omics pan-cancer analysis focused on the diagnosis, prognosis, immune cell infiltration, methylation, and anti-cancer drug sensitivity remains an enigma. The effect of C8orf76 on lung adenocarcinoma (LUAD) is unknown.
Multi-omics pan-cancer analysis by utilizing datasets including UALCAN, TIMER 2.0, Human Protein Atlas (HPA), The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), cBioPortal, Gene Expression Profiling Interactive Analysis (GEPIA), OncoDB, and MethSurv datasets, were conducted to analyze C8orf76 across 33 cancer types. Furthermore, differential R packages were uesd for an in-depth analysis of C8orf76. The correlation between C8orf76 expression and diagnostic, prognosis, genetic alteration, mRNA modification, DNA methylation, lncRNA-miRNA-C8orf76 regulatory network, immune cell infiltration, and anti-tumor drugs response were explored to evaluate the potential roles of C8orf76. Most importantly, experiments including quantitative polymerase chain reaction (qPCR), RNA interference (RNAi), Western blotting (WB), and Edu staining, were performed for experimental verification.
It was noted that the C8orf76 expression was markedly elevated across multiple tumor types. Moreover, C8orf76 showed potential as a diagnostic and prognostic biomarker. Besides, it was confirmed that the expression of C8orf76 was related to DNA methylation, mRNA modification, and the infiltration of immune cells. The lncRNA-miRNA-C8orf76 network was established in the study of LUAD. Experimental validation in LUAD A549 cells demonstrated that the knockdown of C8orf76 significantly inhibited cell proliferation in LUAD.
The present study is the first to report that the multi-omics pan-cancer analysis predicts C8orf76 as a promising target in cancer prognosis, diagnosis, immunology, and chemotherapy, highlighting its influence on cell proliferation in LUAD with experimental validation.
8号染色体开放阅读框76（C8orf76）是一个编码核蛋白的基因，在当前研究中受到的关注有限。聚焦于诊断、预后、免疫细胞浸润、甲基化和抗癌药物敏感性的多组学泛癌分析仍是一个谜。C8orf76对肺腺癌（LUAD）的影响尚不清楚。
利用包括UALCAN、TIMER 2.0、人类蛋白质图谱（HPA）、癌症基因组图谱（TCGA）、基因型-组织表达（GTEx）、cbioportal、基因表达谱交互分析（GEPIA）、OncoDB和MethSurv数据集在内的数据集进行多组学泛癌分析，以分析33种癌症类型中的C8orf76。此外，使用差异R包对C8orf76进行深入分析。探索C8orf76表达与诊断、预后、基因改变、mRNA修饰、DNA甲基化、lncRNA-miRNA-C8orf76调控网络、免疫细胞浸润和抗肿瘤药物反应之间的相关性，以评估C8orf76的潜在作用。最重要的是，进行了包括定量聚合酶链反应（qPCR）、RNA干扰（RNAi）、蛋白质免疫印迹（WB）和Edu染色在内的实验进行验证。
值得注意的是，C8orf76在多种肿瘤类型中的表达明显升高。此外，C8orf76显示出作为诊断和预后生物标志物的潜力。此外，证实了C8orf76的表达与DNA甲基化、mRNA修饰和免疫细胞浸润有关。在LUAD研究中建立了lncRNA-miRNA-C8orf76网络。在LUAD A549细胞中的实验验证表明，敲低C8orf76可显著抑制LUAD中的细胞增殖。
本研究首次报道多组学泛癌分析预测C8orf76是癌症预后、诊断、免疫学和化疗中有前景的靶点，通过实验验证突出了其对LUAD细胞增殖的影响。
