Identification of A Risk Signature Based on Lactic Acid Metabolism-Related LncRNAs in Patients With Esophageal Squamous Cell Carcinoma

Abstract

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.

Comprehensive Analysis of Molecular Clusters and Prognostic Signature Based on m7G-related LncRNAs in Esophageal Squamous Cell Carcinoma

“…2022-R241) and informed written consent was obtained from all patients. The specific experimental protocol comes from our previous research ( 10 , 11 ).…”

Focus on pattern recognition receptors to identify prognosis and immune microenvironment in colon cancer

“…The study has obtained the approval of The Ethics Committee of the Second Hospital of Hebei Medical University and obtained all patients' written consent. For specific experimental protocols, please refer to previous studies in our hospital (15,16).…”

Novel chemokine related LncRNA signature correlates with the prognosis, immune landscape, and therapeutic sensitivity of esophageal squamous cell cancer

“…Mounting evidence suggested that lncRNAs play an important role in prognosis prediction in ESCC. For example, prognostic signatures such as lactic acid metabolism, ferroptosis-related lncRNA, and m7G-related lncRNA were proved to have favorable prognosis prediction in ESCC [12][13][14]. In addition, lncRNA based model can be used as therapeutic target, which could forecast the effect of immunotherapy or chemotherapy [15,16].…”