Liang Hao, Xiang Lan, Wu Huan, Liu Yang, Tian Wei, Zeng Jianhua
Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Front Pharmacol. 2023 Mar 20;14:1135626. doi: 10.3389/fphar.2023.1135626. eCollection 2023.
Cervical cancer (CC) is a major health threat to females, and distal metastasis is common in patients with advanced CC. Anoikis is necessary for the development of distal metastases. Understanding the mechanisms associated with anoikis in CC is essential to improve its survival rate. The expression matrix of long non-coding RNAs (lncRNAs) from cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) patients was extracted from The Cancer Genome Atlas (TCGA), and highly relevant anoikis-related lncRNAs (ARLs) were identified by the single sample gene set enrichment analysis (ssGSEA) method. ARLs-related molecular subtypes were discerned based on prognosis-related ARLs. ARLs-related prognostic risk score (APR_Score) was calculated and risk model was constructed using LASSO COX and COX models. In addition, we also assessed immune cell activity in the immune microenvironment (TME) for both subtypes and APR_Score groups. A nomogram was utilized for predicting improved clinical outcome. Finally, this study also discussed the potential of ARLs-related signatures in predicting response to immunotherapy and small molecular drugs. Three ARLs-related subtypes were identified from TCGA-CESC (AC1, AC2, and AC3), with AC3 patients having the highest ARG scores, higher angiogenesis scores, and the worst prognosis. AC3 had lower immune cell scores in TME but higher immune checkpoint gene expression and higher potential for immune escape. Next, we constructed a prognostic risk model consisting of 7-ARLs. The APR_Score exhibited a greater robustness as an independent prognostic indicator in predicting prognosis, and the nomogram was a valuable tool for survival prediction. ARLs-related signatures emerged as a potential novel indicator for immunotherapy and small molecular drug selection. We firstly constructed novel ARLs-related signatures capable of predicting prognosis and offered novel ideas for therapy response in CC patients.
宫颈癌(CC)是对女性的重大健康威胁,远处转移在晚期CC患者中很常见。失巢凋亡对于远处转移的发生是必要的。了解CC中与失巢凋亡相关的机制对于提高其生存率至关重要。从癌症基因组图谱(TCGA)中提取宫颈鳞状细胞癌和宫颈内膜腺癌(CESC)患者的长链非编码RNA(lncRNA)表达矩阵,并通过单样本基因集富集分析(ssGSEA)方法鉴定高度相关的失巢凋亡相关lncRNA(ARL)。基于与预后相关的ARL识别出ARL相关的分子亚型。计算ARL相关的预后风险评分(APR_Score),并使用LASSO COX和COX模型构建风险模型。此外,我们还评估了两种亚型和APR_Score组在免疫微环境(TME)中的免疫细胞活性。使用列线图预测改善的临床结果。最后,本研究还讨论了ARL相关特征在预测免疫治疗和小分子药物反应方面的潜力。从TCGA-CESC中鉴定出三种ARL相关亚型(AC1、AC2和AC3),AC3患者的ARL评分最高,血管生成评分更高,预后最差。AC3在TME中的免疫细胞评分较低,但免疫检查点基因表达较高,免疫逃逸潜力较大。接下来,我们构建了一个由7个ARL组成的预后风险模型。APR_Score作为预测预后的独立预后指标表现出更大的稳健性,列线图是生存预测的有价值工具。ARL相关特征成为免疫治疗和小分子药物选择的潜在新指标。我们首先构建了能够预测预后的新型ARL相关特征,并为CC患者的治疗反应提供了新思路。