细胞周期蛋白依赖性激酶抑制剂 2C 表达在癌症中的临床意义：从小细胞肺癌到泛癌。

Clinical significance of cyclin-dependent kinase inhibitor 2C expression in cancers: from small cell lung carcinoma to pan-cancers.

机构信息

Ward of Pulmonary and Critical Care Medicine, Department of Respiratory Medicine, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.

Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China.

出版信息

BMC Pulm Med. 2022 Jun 24;22(1):246. doi: 10.1186/s12890-022-02036-5.

DOI:10.1186/s12890-022-02036-5

PMID:35751045

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9233395/

Abstract

BACKGROUND

Cyclin-dependent kinase inhibitor 2C (CDKN2C) was identified to participate in the occurrence and development of multiple cancers; however, its roles in small cell lung carcinoma (SCLC) remain unclear.

METHODS

Differential expression analysis of CDKN2C between SCLC and non-SCLC were performed based on 937 samples from multiple centers. The prognosis effects of CDKN2C in patients with SCLC were detected using both Kaplan-Meier curves and log-rank tests. Using receiver-operating characteristic curves, whether CDKN2C expression made it feasible to distinguish SCLC was determined. The potential mechanisms of CDKN2C in SCLC were investigated by gene ontology terms and signaling pathways (Kyoto Encyclopedia of Genes and Genomes). Based on 10,080 samples, a pan-cancer analysis was also performed to determine the roles of CDKN2C in multiple cancers.

RESULTS

For the first time, upregulated CDKN2C expression was detected in SCLC samples at both the mRNA and protein levels (p of Wilcoxon rank-sum test < 0.05; standardized mean difference = 2.86 [95% CI 2.20-3.52]). Transcription factor FOXA1 expression may positively regulate CDKN2C expression levels in SCLC. High CDKN2C expression levels were related to the poor prognosis of patients with SCLC (hazard ratio > 1, p < 0.05) and showed pronounced effects for distinguishing SCLC from non-SCLC (sensitivity, specificity, and area under the curve ≥ 0.95). CDKN2C expression may play a role in the development of SCLC by affecting the cell cycle. Furthermore, the first pan-cancer analysis revealed the differential expression of CDKN2C in 16 cancers (breast invasive carcinoma, etc.) and its independent prognostic significance in nine cancers (e.g., adrenocortical carcinoma). CDKN2C expression was related to the immune microenvironment, suggesting its potential usefulness as a prognostic marker in immunotherapy.

CONCLUSIONS

This study identified upregulated CDKN2C expression and its clinical significance in SCLC and other multiple cancers, suggesting its potential usefulness as a biomarker in treating and differentiating cancers.

摘要

背景

细胞周期蛋白依赖性激酶抑制剂 2C（CDKN2C）被鉴定参与多种癌症的发生和发展；然而，其在小细胞肺癌（SCLC）中的作用尚不清楚。

方法

基于来自多个中心的 937 个样本，对 SCLC 和非 SCLC 之间的 CDKN2C 差异表达进行分析。使用 Kaplan-Meier 曲线和对数秩检验检测 CDKN2C 对 SCLC 患者的预后影响。通过接收者操作特征曲线，确定 CDKN2C 表达是否可以区分 SCLC。通过基因本体术语和信号通路（京都基因与基因组百科全书）来研究 CDKN2C 在 SCLC 中的潜在机制。基于 10080 个样本，还进行了泛癌症分析，以确定 CDKN2C 在多种癌症中的作用。

结果

首次在 SCLC 样本中检测到 CDKN2C 的 mRNA 和蛋白质水平均上调（Wilcoxon 秩和检验的 p 值<0.05；标准化平均差=2.86 [95%置信区间 2.20-3.52]）。转录因子 FOXA1 的表达可能正向调节 SCLC 中 CDKN2C 的表达水平。高 CDKN2C 表达水平与 SCLC 患者的不良预后相关（风险比>1，p<0.05），并且对区分 SCLC 与非 SCLC 具有显著效果（灵敏度、特异性和曲线下面积≥0.95）。CDKN2C 表达可能通过影响细胞周期在 SCLC 的发生发展中发挥作用。此外，首次泛癌症分析显示 CDKN2C 在 16 种癌症（乳腺浸润性癌等）中的表达差异及其在 9 种癌症（如肾上腺皮质癌）中的独立预后意义。CDKN2C 表达与免疫微环境相关，提示其作为免疫治疗预后标志物的潜在用途。