Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, 250012, P.R. China.
Cheeloo College of Medicine, Shandong University, Jinan, China.
World J Surg Oncol. 2024 Oct 10;22(1):273. doi: 10.1186/s12957-024-03558-4.
Ficolins (FCNs) are a family of proteins, comprising FCN1, FCN2 and FCN3, and integral to the immune system which have been implicated in the onset and progression of tumors. Despite their recognized roles, a comprehensive analysis of FCNs in lung cancer remains elusive.
We employed a variety of bioinformatics tools, including UCSC, SangerBox, Ualcan, cBioPortal, String, Metascape, GeneMANIA, TIDE, CTD, and CAMP databases to investigate the differential expression, diagnostic and prognostic significance, genetic alterations, functional enrichment, immune infiltration, and potential immunotherapeutic implications of FCN1, FCN2, and FCN3 in lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD). Additionally, RT-qPCR and immunohistochemistry were utilized to validate the expressions of FCNs at the mRNA and protein levels in LUSC and LUAD.
Our comprehensive bioinformatic analysis, supported by RT-qPCR and immunohistochemistry, revealed that the expressions of FCN1, FCN2 and FCN3 were consistently downregulated in both LUSC and LUAD tumor tissues. FCNs demonstrated significant diagnostic potential for LUSC and LUAD, with the area under the receiver operating characteristic curve (AUC) for FCN1 and FCN3 exceeding 0.90. Furthermore, FCN2 and FCN3 showed a strong negative correlation with overall survival (OS) in LUSC, whereas FCN1 and FCN2 were positively correlated with OS in LUAD, suggesting their prognostic value in lung cancer. Gene enrichment analysis indicated that FCNs were predominantly associated with the complement system and complement activation pathways. Immune infiltration analysis further revealed a significant positive correlation between FCNs and the presence of neutrophils and resting mast cells. Our analysis of immunotherapy outcomes revealed a significant disparity in the immunophenoscore (IPS) among lung cancer patients treated with immune checkpoint inhibitors (ICIs), distinguishing those with high FCN expression from those with low FCN expression. Additionally, we identified small molecule compounds related to FCNs and drugs pertinent to LUSC and LUAD.
FCNs held promise as diagnostic and prognostic biomarkers for LUSC and LUAD. This study also elucidated the relationship of FCNs with the tumor microenvironment, offering novel insights into the immunotherapeutic landscape for LUSC and LUAD.
ficolins（FCNs）是一组蛋白质，包括 FCN1、FCN2 和 FCN3，它们是免疫系统的重要组成部分，与肿瘤的发生和发展有关。尽管它们的作用已经得到了认可，但对 FCN 在肺癌中的全面分析仍然难以捉摸。
我们使用了多种生物信息学工具，包括 UCSC、SangerBox、Ualcan、cBioPortal、String、Metascape、GeneMANIA、TIDE、CTD 和 CAMP 数据库，来研究 FCN1、FCN2 和 FCN3 在肺鳞状细胞癌（LUSC）和肺腺癌（LUAD）中的差异表达、诊断和预后意义、遗传改变、功能富集、免疫浸润以及潜在的免疫治疗意义。此外，我们还利用 RT-qPCR 和免疫组织化学来验证 FCNs 在 LUSC 和 LUAD 中的 mRNA 和蛋白水平的表达。
我们的综合生物信息学分析，得到了 RT-qPCR 和免疫组织化学的支持，显示 FCN1、FCN2 和 FCN3 的表达在 LUSC 和 LUAD 肿瘤组织中均下调。FCNs 对 LUSC 和 LUAD 具有显著的诊断潜力，FCN1 和 FCN3 的受试者工作特征曲线（ROC）下面积（AUC）超过 0.90。此外，FCN2 和 FCN3 与 LUSC 的总生存期（OS）呈强负相关，而 FCN1 和 FCN2 与 LUAD 的 OS 呈正相关，表明它们在肺癌中的预后价值。基因富集分析表明，FCNs 主要与补体系统和补体激活途径有关。免疫浸润分析进一步显示，FCNs 与中性粒细胞和静止肥大细胞的存在呈显著正相关。我们对免疫治疗结果的分析显示，接受免疫检查点抑制剂（ICIs）治疗的肺癌患者的免疫表型评分（IPS）存在显著差异，将高 FCN 表达的患者与低 FCN 表达的患者区分开来。此外，我们还鉴定了与 FCN 相关的小分子化合物以及与 LUSC 和 LUAD 相关的药物。
FCNs 有望成为 LUSC 和 LUAD 的诊断和预后生物标志物。本研究还阐明了 FCNs 与肿瘤微环境的关系，为 LUSC 和 LUAD 的免疫治疗提供了新的见解。
