Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, 350001, China.
Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, Fujian, 350001, China.
BMC Cancer. 2023 Sep 25;23(1):899. doi: 10.1186/s12885-023-11405-0.
Studies have demonstrated that Sorting nexin 7 (SNX7) functions as an anti-apoptotic protein in liver tissue and plays a crucial role in the survival of hepatocytes during early embryonic development. However, its diagnostic and prognostic value as well as the predictive value of chemotherapy and immunotherapy have not been reported in hepatocellular carcinoma (HCC).
SNX7 mRNA expression and its diagnostic efficacy were examined in GEO datasets, and the findings were further confirmed in TCGA, ICGC cohorts, and cell lines. The protein level of SNX7 was determined using CPTAC and HPA databases, and the results were validated through immunohistochemistry (IHC). Survival analyses were performed in TCGA and ICGC cohorts, and the results were subsequently validated via Kaplan-Meier Plotter. The response to chemotherapy and immunotherapy was predicted via GDSC dataset and TIDE algorithm, respectively. R packages were employed to explore the relationship between SNX7 expression and immune infiltration, m6A modification, as well as the functional enrichment of differentially expressed genes (DEGs).
The expression of SNX7 at both mRNA and protein levels was significantly upregulated in HCC tissues. SNX7 exhibited superior diagnostic efficacy compared to AFP alone for HCC detection, and combining it with AFP improved the diagnostic accuracy for HCC. High SNX7 was associated with unfavorable outcomes, including poor overall survival, disease-specific survival, progression-free survival, and advanced pathological stage, in patients with HCC, and SNX7 was identified as an independent risk factor for HCC. Moreover, elevated SNX7 expression was positively correlated with increased sensitivity to various chemotherapy drugs, including sorafenib, while it was associated with resistance to immunotherapy in HCC patients. Correlation analysis revealed a relationship between SNX7 and multiple m6A-related genes and various immune cells. Finally, enrichment analysis demonstrated strong associations of SNX7 with critical biological processes, such as cell cycle regulation, cellular senescence, cell adhesion, DNA replication, and mismatch repair pathway in HCC.
Our study highlights the association of SNX7 with the immune microenvironment and its potential influence on HCC progression. SNX7 emerges as a promising novel biomarker for the diagnosis, prognosis, and prediction of response to chemotherapy and immunotherapy in patients with HCC.
研究表明，分选连接蛋白 7（SNX7）在肝组织中作为一种抗凋亡蛋白发挥作用，在早期胚胎发育过程中对肝细胞的存活起着至关重要的作用。然而，在肝细胞癌（HCC）中，其诊断和预后价值以及化疗和免疫治疗的预测价值尚未被报道。
在 GEO 数据集中检查 SNX7mRNA 的表达及其诊断效能，并在 TCGA、ICGC 队列和细胞系中进一步证实。使用 CPTAC 和 HPA 数据库确定 SNX7 的蛋白水平，并通过免疫组化（IHC）验证结果。在 TCGA 和 ICGC 队列中进行生存分析，并通过 Kaplan-Meier Plotter 进行验证。通过 GDSC 数据集和 TIDE 算法分别预测对化疗和免疫治疗的反应。使用 R 包探索 SNX7 表达与免疫浸润、m6A 修饰以及差异表达基因（DEGs）的功能富集之间的关系。
SNX7 在 HCC 组织中的 mRNA 和蛋白水平表达均显著上调。SNX7 对 HCC 的检测具有优于 AFP 的诊断效能，与 AFP 联合使用可提高 HCC 的诊断准确性。高 SNX7 与 HCC 患者的不良结局相关，包括总生存期、疾病特异性生存期、无进展生存期和晚期病理分期不佳，SNX7 被确定为 HCC 的独立危险因素。此外，SNX7 表达升高与多种化疗药物（包括索拉非尼）的敏感性增加相关，而与 HCC 患者的免疫治疗耐药相关。相关性分析显示 SNX7 与多种 m6A 相关基因和多种免疫细胞之间存在相关性。最后，富集分析表明 SNX7 与 HCC 中关键的生物学过程（如细胞周期调控、细胞衰老、细胞黏附、DNA 复制和错配修复途径）密切相关。
本研究强调了 SNX7 与免疫微环境的关联及其对 HCC 进展的潜在影响。SNX7 作为一种有前途的新型生物标志物，可用于 HCC 患者的诊断、预后和预测对化疗和免疫治疗的反应。
