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Background: Epithelial-mesenchymal transition (EMT) plays a vital role in tumor metastasis and drug resistance. It has been reported that EMT is regulated by several long noncoding RNAs (lncRNAs). We aimed to identify EMT-related lncRNAs and develop an EMT-related lncRNA prognostic signature in kidney renal clear cell carcinoma (KIRC)., Materials and Methods: In total, 530 ccRCC patients with 611 transcriptome profiles were included in this study. We first identified differentially expressed EMT-related lncRNAs. Then, all the samples with transcriptional data and clinical survival information were randomly split into training/test sets at a ratio of 1 : 1. Accordingly, we further developed a twelve differentially expressed EMT-related lncRNA prognostic signature in the training set. Following this, risk analysis, survival analysis, subgroup analysis, and the construction of the ROC curves were applied to verify the efficacy of the signature in the training set, test set, and all patients. Besides, we further investigated the differential immune infiltration, immune checkpoint expression, and immune-related functions between high-risk patients. Finally, we explored the different drug responses to targeted therapy (sunitinib and sorafenib) and immunotherapy (anti-PD1 and anti-CTLA4)., Results: A twelve differentially expressed EMT-related lncRNA prognostic signature performed superior in predicting the overall survival of KIRC patients. High-risk patients were observed with a significantly higher immune checkpoint expression and showed better responses to the targeted therapy and immunotherapy., Conclusions: Our study demonstrates that the twelve differentially expressed EMT-related lncRNA prognostic signature could act as an efficient prognostic indicator for KIRC, which also contributes to the decision-making of the further treatment., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Qi-Dong Xia et al.)

Background: Renal cell carcinoma (RCC) is one of the most common aggressive malignant tumors in the urinary system, among which the clear cell renal cell carcinoma (ccRCC) is the most common subtype. The immune-related long noncoding ribonucleic acids (irlncRNAs) which are abundant in immune cells and immune microenvironment (IME) have potential significance in evaluating the prognosis and effects of immunotherapy. The signature based on irlncRNA pairs and independent of the exact expression level seems to have a latent predictive significance for the prognosis of patients with malignant tumors but has not been applied in ccRCC yet., Method: In this article, we retrieved The Cancer Genome Atlas (TCGA) database for the transcriptome profiling data of the ccRCC and performed coexpression analysis between known immune-related genes (ir-genes) and lncRNAs to find differently expressed irlncRNA (DEirlncRNA). Then, we adopted a single-factor test and a modified LASSO regression analysis to screen out ideal DEirlncRNAs and constructed a Cox proportional hazard model. We have sifted 28 DEirlncRNA pairs, 12 of which were included in this model. Next, we compared the area under the curve (AUC), found the cutoff point by using the Akaike information criterion (AIC) value, and distinguished the patients with ccRCC into a high-risk group and a low-risk group using this value. Finally, we tested this model by investigating the relationship between risk score and survival, clinical pathological characteristics, cells in tumor immune microenvironment, chemotherapy, and targeted checkpoint biomarkers., Results: A novel immune-related lncRNA pair signature consisting of 12 DEirlncRNA pairs was successfully constructed and tightly associated with overall survival, clinical pathological characteristics, cells in tumor immune microenvironment, and reactiveness to immunotherapy and chemotherapy in patients with ccRCC. Besides, the efficacy of this signature was verified in some commonly used clinicopathological subgroups and could serve as an independent prognostic factor in patients with ccRCC., Conclusions: This signature was proven to have a potential predictive significance for the prognosis of patients with ccRCC and the efficacy of immunotherapy., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Jian-Xuan Sun et al.)

Background: Redox plays an essential role in the pathogeneses and progression of tumors, which could be regulated by long noncoding RNA (lncRNA). We aimed to develop and verify a novel redox-related lncRNA-based prognostic signature for clear cell renal cell carcinoma (ccRCC)., Materials and Methods: A total of 530 ccRCC patients from The Cancer Genome Atlas (TCGA) were included in this study. All the samples were randomly split into training and test group at a 1 : 1 ratio. Then, we screened differentially expressed redox-related lncRNAs and constructed a novel prognostic signature from the training group using the least absolute shrinkage and selection operation (LASSO) and COX regression. Next, to verify the accuracy of the signature, we conducted risk and survival analysis, as well as the construction of ROC curve, nomogram, and calibration curves in the training group, test group, and all samples. Finally, the redox gene-redox-related lncRNA interaction network was constructed, and gene set enrichment analysis (GSEA) was performed to investigate the status of redox-related functions between high/low-risk groups., Results: A nine-redox-related lncRNA signature consisted of AC025580.3 , COLCA1 , AC027601.2 , DLEU2 , AC004918.3 , AP006621.2 , AL031670.1 , SPINT1-AS1 , and LAMA5-AS1 was significantly associated with overall survival in ccRCC patients. The signature proved efficient, and thus, a nomogram was successfully assembled. In addition, the GSEA results demonstrated that two major redox-related functions were enhanced in the high-risk group ccRCC patients., Conclusions: Our findings robustly demonstrate that the nine-redox-related lncRNA signature could serve as an efficient prognostic indicator for ccRCC., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Xia Qi-Dong et al.)