Zhao Fangchao, Li Yishuai, Dong Zefang, Zhang Dengfeng, Guo Pengfei, Li Zhirong, Li Shujun
Department of Thoracic Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Thoracic Surgery, Hebei Chest Hospital, Shijiazhuang, China.
Front Cell Dev Biol. 2022 May 12;10:845293. doi: 10.3389/fcell.2022.845293. eCollection 2022.
Lactic acid, formerly thought of as a byproduct of glycolysis or a metabolic waste produced, has now been identified as a key regulator of cancer growth, maintenance, and progression. However, the results of investigations on lactic acid metabolism-related long non-coding RNAs (LRLs) in esophageal squamous cell carcinoma (ESCC) remain inconclusive. In this study, univariate Cox regression analysis was carried out in the TCGA cohort, and 9 lncRNAs were shown to be significantly associated with prognosis. Least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate Cox regression analysis were then used in the GEO cohort. 6 LRLs were identified as independent prognostic factors for ESCC patients used to construct a prognostic risk-related signature subsequently. Two groups were formed based on the middle value of risk scores: a low-risk group and a high-risk group. Following that, we conducted Kaplan-Meier survival analysis, which revealed that the high-risk group had a lower survival probability than the low-risk group in both GEO and TCGA cohorts. On multivariate Cox regression analysis, the prognostic signature was shown to be independent prognostic factor, and it was found to be a better predictor of the prognosis of ESCC patients than the currently widely used grading and staging approaches. The established nomogram can be conveniently applied in the clinic to predict the 1-, 3-, and 5- year survival rates of patients. There was a significant link found between the 6 LRLs-based prognostic signature and immune-cell infiltration, tumor microenvironment (TME), tumor somatic mutational status, and chemotherapeutic treatment sensitivity in the study population. Finally, we used GTEx RNA-seq data and qRT-PCR experiments to verify the expression levels of 6 LRLs. In conclusion, we constructed a prognostic signature which could predict the prognosis and immunotherapy response of ESCC patients.
乳酸，以前被认为是糖酵解的副产物或产生的代谢废物，现在已被确定为癌症生长、维持和进展的关键调节因子。然而，关于食管鳞状细胞癌（ESCC）中乳酸代谢相关长链非编码RNA（LRL）的研究结果仍无定论。在本研究中，对TCGA队列进行了单变量Cox回归分析，结果显示9种lncRNA与预后显著相关。随后在GEO队列中使用最小绝对收缩和选择算子（LASSO）回归分析和多变量Cox回归分析。6种LRL被确定为ESCC患者的独立预后因素，随后用于构建预后风险相关特征。根据风险评分的中位数分为两组：低风险组和高风险组。随后，我们进行了Kaplan-Meier生存分析，结果显示在GEO和TCGA队列中，高风险组的生存概率均低于低风险组。多变量Cox回归分析显示，预后特征是独立的预后因素，并且发现它比目前广泛使用的分级和分期方法更能预测ESCC患者的预后。所建立的列线图可方便地应用于临床，以预测患者的1年、3年和5年生存率。在研究人群中，基于6种LRL的预后特征与免疫细胞浸润、肿瘤微环境（TME）、肿瘤体细胞突变状态和化疗敏感性之间存在显著关联。最后，我们使用GTEx RNA-seq数据和qRT-PCR实验验证了6种LRL的表达水平。总之，我们构建了一个可以预测ESCC患者预后和免疫治疗反应的预后特征。
