生物信息学评估鉴定的非小细胞肺癌组织蛋白酶 F 的表达特征、预后价值和免疫特征。
Expression signature, prognosis value and immune characteristics of cathepsin F in non-small cell lung cancer identified by bioinformatics assessment.
机构信息
Department of Medical Biology, School of Basic Medical Science, Hubei University of Medicine, Shiyan, 442000, Hubei Province, China.
Institute of Biomedical Research, Hubei University of Medicine, Shiyan, 442000, Hubei Province, China.
出版信息
BMC Pulm Med. 2021 Dec 20;21(1):420. doi: 10.1186/s12890-021-01796-w.
BACKGROUND
In recent years, immunotherapies and targeted therapies contribute to population-level improvement in NSCLC cancer-specific survival, however, the two novel therapeutic options have mainly benefit patients containing mutated driven genes. Thus, to explore other potential genes related with immunity or targeted therapies may provide novel options to improve survival of lung cancer patients without mutated driven genes. CTSF is unique in human cysteine proteinases. Presently, CTSF has been detected in several cell lines of lung cancer, but its role in progression and prognosis of lung cancer remains unclear.
METHODS
CTSF expression and clinical datasets of lung cancer patients were obtained from GTEx, TIMER, CCLE, THPA, and TCGA, respectively. Association of CTSF expression with clinicopathological parameters and prognosis of lung cancer patients was analyzed using UALCAN and Kaplan-Meier Plotter, respectively. LinkedOmics were used to analyze correlation between CTSF and CTSF co-expressed genes. Protein-protein interaction and gene-gene interaction were analyzed using STRING and GeneMANIA, respectively. Association of CTSF with molecular markers of immune cells and immunomodulators was analyzed with Immunedeconv and TISIDB, respectively.
RESULTS
CTSF expression was currently only available for patients with NSCLC. Compared to normal tissues, CTSF was downregulated in NSCLC samples and high expressed CTSF was correlated with favorable prognosis of NSCLC. Additionally, CTSF expression was correlated with that of immune cell molecular markers and immunomodulators both in LUAD and LUSC. Noticeably, high expression of CTSF-related CTLA-4 was found to be associated with better OS of LUAD patients. Increased expression of CTSF-related LAG-3 was related with poor prognosis of LUAD patients while there was no association between CTSF-related PD-1/PD-L1 and prognosis of LUAD patients. Moreover, increased expression of CTSF-related CD27 was related with poor prognosis of LUAD patients while favorable prognosis of LUSC patients.
CONCLUSIONS
CTSF might play an anti-tumor effect via regulating immune response of NSCLC.
背景
近年来，免疫疗法和靶向治疗使 NSCLC 癌症特异性生存的人群水平得到改善，然而，这两种新的治疗选择主要使携带突变驱动基因的患者受益。因此，探索其他与免疫或靶向治疗相关的潜在基因可能为改善无突变驱动基因的肺癌患者的生存提供新的选择。CTSF 在人类半胱氨酸蛋白酶中是独特的。目前，CTSF 已在几种肺癌细胞系中被检测到，但它在肺癌的进展和预后中的作用尚不清楚。
方法
分别从 GTEx、TIMER、CCLE、THPA 和 TCGA 获得 CTSF 表达和肺癌患者的临床数据集。使用 UALCAN 和 Kaplan-Meier Plotter 分别分析 CTSF 表达与肺癌患者临床病理参数和预后的关系。使用 LinkedOmics 分析 CTSF 与 CTSF 共表达基因之间的相关性。使用 STRING 和 GeneMANIA 分别分析蛋白质-蛋白质相互作用和基因-基因相互作用。使用 Immunedeconv 和 TISIDB 分别分析 CTSF 与免疫细胞和免疫调节剂的分子标志物的关系。
结果
目前只有 NSCLC 患者的 CTSF 表达数据。与正常组织相比，NSCLC 样本中 CTSF 表达下调，高表达 CTSF 与 NSCLC 的良好预后相关。此外，在 LUAD 和 LUSC 中，CTSF 表达与免疫细胞分子标志物和免疫调节剂均相关。值得注意的是，CTSF 相关 CTLA-4 的高表达与 LUAD 患者的 OS 相关。CTSF 相关 LAG-3 的高表达与 LUAD 患者的不良预后相关，而 CTSF 相关 PD-1/PD-L1 与 LUAD 患者的预后无关。此外，CTSF 相关 CD27 的高表达与 LUAD 患者的不良预后相关，而 LUSC 患者的预后较好。
结论
CTSF 可能通过调节 NSCLC 的免疫反应发挥抗肿瘤作用。
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