Xu Dandan, Chen Xiao, Wu Mingyuan, Bi Jinfeng, Xue Hua, Chen Hong
Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Geriatric Respiratory Medicine, Heilongjiang Provincial Hospital, Harbin, China.
Heliyon. 2024 Mar 21;10(7):e28278. doi: 10.1016/j.heliyon.2024.e28278. eCollection 2024 Apr 15.
Globally, lung carcinoma remains the leading cause of death, with its associated morbidity and mortality rates remaining elevated. Despite the slow advancement of treatment, the outlook remains bleak. Cellular senescence represents a halt in the cell cycle, encompassing a range of physiological and pathological activities, along with diverse phenotypic alterations, including variations in secretory phenotype, macromolecular harm, and metabolic disturbances. Research has revealed its vital function in the formation and growth of tumors. This study aimed to examine cellular senescence-related mRNAs linked to the outlook of non-small cell lung cancer (NSCLC) and to formulate a predictive risk framework for NSCLC.
We acquired the NSCLC expression data from The Cancer Genome Atlas (TCGA) to examine mRNAs linked to cellular senescence. Both single-variable and multiple-variable cox proportion risk assessments were utilized to determine the traits of cellular senescence-related mRNAs linked to NSCLC prognosis. Subsequently, the prognostic model for cellular senescence-related mRNAs was integrated with clinical-pathological characteristics to create a prognostic nomogram. Furthermore, the study delved into the risk-oriented predictive model, examining immune infiltration and responses to immunotherapy among both high and low-risk categories.
Utilizing both univariate and multivariate Cox proportion risk assessments, a risk model comprising 12 mRNAs associated with cellular aging was ultimately developed: . Univariate analysis and multivariate analysis illustrated that the risk score served as a standalone indicator for prognosis, and the hazard ratio (HR) of the risk score were 1.182 (1.139-1.226) (p < 0.001) and 1.162 (1.119 - 1.206) (p < 0.001), respectively. Individual prognoses were forecasted using nomogram, c-index, and principal component analysis (PCA). Furthermore, the risk-oriented model revealed notable statistical variances in immune infiltration and response to immunotherapy among the high and low risk categories.
This study shows that mRNAs related to cell senescence associated with prognosis are reliable predictors of NSCLC immunotherapy reaction and prognosis.
在全球范围内，肺癌仍然是主要的死亡原因，其相关的发病率和死亡率居高不下。尽管治疗进展缓慢，但前景依然黯淡。细胞衰老代表细胞周期的停滞，涵盖一系列生理和病理活动，以及多种表型改变，包括分泌表型的变化、大分子损伤和代谢紊乱。研究表明其在肿瘤的形成和生长中起着至关重要的作用。本研究旨在检测与非小细胞肺癌（NSCLC）预后相关的细胞衰老相关mRNA，并构建NSCLC的预测风险框架。
我们从癌症基因组图谱（TCGA）获取NSCLC表达数据，以检测与细胞衰老相关的mRNA。采用单变量和多变量cox比例风险评估来确定与NSCLC预后相关的细胞衰老相关mRNA的特征。随后，将细胞衰老相关mRNA的预后模型与临床病理特征相结合，创建一个预后列线图。此外，该研究深入探讨了以风险为导向的预测模型，研究了高风险和低风险类别中的免疫浸润和免疫治疗反应。
通过单变量和多变量Cox比例风险评估，最终建立了一个包含12个与细胞衰老相关的mRNA的风险模型：。单变量分析和多变量分析表明，风险评分是预后的独立指标，风险评分的风险比（HR）分别为1.182（1.139 - 1.226）（p < 0.001）和1.162（1.119 - 1.206）（p < 0.001）。使用列线图、c指数和主成分分析（PCA）预测个体预后。此外，以风险为导向的模型显示，高风险和低风险类别在免疫浸润和免疫治疗反应方面存在显著的统计学差异。
本研究表明，与预后相关的细胞衰老相关mRNA是NSCLC免疫治疗反应和预后的可靠预测指标。
