Prognostic Value of a Long Non-coding RNA Signature in Localized Clear Cell Renal Cell Carcinoma.

Long non-coding RNAs (lncRNAs) can be used as prognostic biomarkers in many types of cancer. We sought to establish an lncRNA signature to improve postoperative risk stratification for patients with localized clear cell renal cell carcinoma (ccRCC). Based on the RNA-seq data of 444 stage I-III ccRCC tumours from The Cancer Genome Atlas project, we built a four-lncRNA-based classifier using the least absolute shrinkage and selection operation (LASSO) Cox regression model in 222 randomly selected samples (training set) and validated the classifier in the remaining 222 samples (internal validation set). We confirmed this classifier in an external validation set of 88 patients with stage I-III ccRCC from a Japan cohort and using quantitative reverse transcription polymerase chain reaction (RT-PCR) in another three independent sets that included 1869 patients from China with stage I-III ccRCC. Univariable and multivariable Cox regression, Harrell's concordance index (c-index), and time-dependent receiver operating characteristic curves were used to evaluate the association of the classifier with overall survival, disease-specific survival, and disease-free survival. Using the LASSO Cox regression model, we built a classifier named RCClnc4 based on four lncRNAs: ENSG00000255774, ENSG00000248323, ENSG00000260911, and ENSG00000231666. In the RNA-seq and RT-PCR data sets, the RCClnc4 signature significantly stratified patients into high-risk versus low-risk groups in terms of clinical outcome across and within subpopulations and remained as an independent prognostic factor in multivariate analyses (hazard ratio range, 1.34 [95% confidence interval {CI}: 1.03-1.75; p=0.028] to 1.89 [95% CI, 1.55-2.31; p<0.001]) after adjusting for clinical and pathologic factors. The RCClnc4 signature achieved a higher accuracy (mean c-index, 0.72) than clinical staging systems such as TNM (mean c-index, 0.62) and the stage, size, grade, and necrosis (SSIGN) score (mean c-index, 0.64), currently reported prognostic signatures and biomarkers for the estimation of survival. When integrated with clinical characteristics, the composite clinical and lncRNA signature showed improved prognostic accuracy in all data sets (TNM + RCClnc4 mean c-index, 0.75; SSIGN + RCClnc4 score mean c-index, 0.75). The RCClnc4 classifier was able to identify a clinically significant number of both high-risk stage I and low-risk stage II-III patients. The RCClnc4 classifier is a promising and potential prognostic tool in predicting the survival of patients with stage I-III ccRCC. Combining the lncRNA classifier with clinical and pathological parameters allows for accurate risk assessment in guiding clinical management. The RCClnc4 classifier could facilitate patient management and treatment decisions.

Qu L ，Wang ZL ，Chen Q ，Li YM ，He HW ，Hsieh JJ ，Xue S ，Wu ZJ ，Liu B ，Tang H ，Xu XF ，Xu F ，Wang J ，Bao Y ，Wang AB ，Wang D ，Yi XM ，Zhou ZK ，Shi CJ ，Zhong K ，Sheng ZC ，Zhou YL ，Jiang J ，Chu XY ，He J ，Ge JP ，Zhang ZY ，Zhou WQ ，Chen C ，Yang JH ，Sun YH ，Wang LH ... -  《-》

Identification of a glycolysis-related lncRNA prognostic signature for clear cell renal cell carcinoma.

The present study investigated the independent prognostic value of glycolysis-related long noncoding (lnc)RNAs in clear cell renal cell carcinoma (ccRCC). A coexpression analysis of glycolysis-related mRNAs-long noncoding RNAs (lncRNAs) in ccRCC from The Cancer Genome Atlas (TCGA) was carried out. Clinical samples were randomly divided into training and validation sets. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to establish a glycolysis risk model with prognostic value for ccRCC, which was validated in the training and validation sets and in the whole cohort by Kaplan-Meier, univariate and multivariate Cox regression, and receiver operating characteristic (ROC) curve analyses. Principal component analysis (PCA) and functional annotation by gene set enrichment analysis (GSEA) were performed to evaluate the risk model. We identified 297 glycolysis-associated lncRNAs in ccRCC; of these, 7 were found to have prognostic value in ccRCC patients by Kaplan-Meier, univariate and multivariate Cox regression, and ROC curve analyses. The results of the GSEA suggested a close association between the 7-lncRNA signature and glycolysis-related biological processes and pathways. The seven identified glycolysis-related lncRNAs constitute an lncRNA signature with prognostic value for ccRCC and provide potential therapeutic targets for the treatment of ccRCC patients.

Ma W ，Zhong M ，Liu X 《-》

Comprehensive analysis of a novel lncRNA profile reveals potential prognostic biomarkers in clear cell renal cell carcinoma.

Liu T ，Sui J ，Zhang Y ，Zhang XM ，Wu WJ ，Yang S ，Xu SY ，Hong WW ，Peng H ，Yin LH ，Pu YP ，Liang GY ... -  《-》

External validation of the Mayo Clinic stage, size, grade, and necrosis (SSIGN) score for clear-cell renal cell carcinoma in a single European centre applying routine pathology.

Zigeuner R ，Hutterer G ，Chromecki T ，Imamovic A ，Kampel-Kettner K ，Rehak P ，Langner C ，Pummer K ... -  《-》

A long non-coding RNA signature to improve prognostic prediction in clear cell renal cell carcinoma.

Accumulating research reports have indicated that long non-coding RNAs (lncRNAs) are abnormally expressed in many types of cancers. However, few lncRNA signatures for predicting cancer prognosis have been established. Our goal is to establish a lncRNA signature for predicting the prognosis of clear cell renal cell carcinoma (ccRCC). We downloaded KIRC lncRNA FPKM (Fragments Per Kilobase of transcript per Million Fragments) standardized expression data from The Cancer Genome Atlas (TCGA) by using the TANRIC tool. We established an 11-lncRNA signature that was clearly linked to the overall survival (OS) rates in the training and test sets. The training set was divided into the high-risk and low-risk subgroups, between which the OS was disparate (HR = 1.51, 95%CI = 1.39-1.64, P < 0.0001). The accuracy of the 11-lncRNA signature for predicting prognosis was confirmed in the test set. Further analysis revealed that the prognostic value of this signature was independent of the neoplasm grade and TNM stage. Gene set enrichment analysis (GSEA) was performed, and a summary of 4 gene sets related to canonical pathway, biological process, molecular function and cellular component was obtained. We demonstrated the biological function of these lncRNAs in ccRCC cell lines and found that LINC00488 and HOTTIP promoted tumour proliferation and inhibited apoptosis. However, LINC-PINT had the opposite effect. The establishment of the 11-lncRNA signature indicated the underlying biochemical functional roles of the selected lncRNAs in ccRCC. Our results may provide a reliable theoretical basis for clinical evaluation of ccRCC prognosis.

Zhang J ，Zhang X ，Piao C ，Bi J ，Zhang Z ，Li Z ，Kong C ... -  《-》