Investigating the diagnostic performance of HOTTIP, PVT1, and UCA1 long noncoding RNAs as a predictive panel for the screening of colorectal cancer patients with lymph node metastasis

• Published in: Journal of cellular biochemistry 2019-09, Vol.120 (9), p.14780-14790
• Main Authors: Gharib, Ehsan, Anaraki, Fakhrosadat, Baghdar, Kaveh, Ghavidel, Pegah, Sadeghi, Hossein, Nasrabadi, Parinaz Nasri, Peyravian, Noshad, Aghdaei, Hamid Asadzadeh, Zali, Mohammad Reza, Mojarad, Ehsan Nazemalhosseini
• Format: Article
• Language: English
• Subjects: biomarker; Biomarkers; Bladder cancer; Cancer; Colorectal cancer; Colorectal carcinoma; Confidence intervals; Diagnostic systems; HOTTIP; lymph node metastasis; Lymph nodes; Lymphatic system; Metastases; Metastasis; Plasmacytoma; PVT1; Screening; Survival; Survival analysis; Training; Transcription; Translocation; UCA1; Urothelial carcinoma
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.28739

Like other noncoding RNAs (ncRNAs), dysregulation of long ncRNAs (lncRNAs) has been associated with various clinicopathological features of colorectal cancer (CRC) patients such as lymph node metastasis (LNM). Recently, three aberrant expressed oncogenic lncRNA (onco‐lncRNAs), including HOXA transcript at the distal tip (HOTTIP), plasmacytoma variant translocation 1 (PVT1), and urothelial carcinoma associated 1 (UCA1) have been reported in LNM. Herein, we compared the diagnostic performance of these lncRNAs as individual biomarkers and as a discriminating panel between LNM CRC patients, nonmetastatic lymph nodes (NLN) and normal healthy subjects. The lncRNAs expression level was measured by quantitative real‐time PCR and analyzed by the Mann‐Whitney U test. The receiver operating characteristic (ROC) curve analysis was applied to evaluate the diagnostic power. The Kaplan‐Meier survival analysis was performed to outline the overall survival (OS) of CRC patients with an abnormal level of lncRNAs. The area under the ROC curve (AUC) of the overexpressed HOTTIP (0.7817; 95% CI, 0.6809‐0.8824), PVT1 (0.8559; 95% CI, 0.7737‐0.9382), and UCA1 (0.8135; 95% CI, 0.722‐0.9051) introduced them as individual CRC biomarkers. As a predictive panel, the AUC values of the HOTTIP, PVT1, and UCA1 for training set were 0.9256 (95% CI, 0.8634‐0.9879; all CRCs), 0.8708 (95% CI, 0.7709‐0.9378; NLN) and 0.9804 (95% CI, 0.9585‐0.9998; LNM), and for validation set were 0.9286 (95% CI, 0.8752‐0.9820; all CRCs), 0.8911 (95% CI, 0.8238‐0.9585; NLN), and 0.9833 (95% CI, 0.9642‐1.002; LNM), respectively. Also, HOTTIP/PVT1/UCA1 panel dysregulation had a marked correlation with patient's OS in training set (logrank test P = 0.0121; hazard ratio [HR], 0.1225; 95% confidence interval [CI], 0.02376‐0.6312), and in validation set (logrank test P < 0.0001, HR, 0.2003; 95% CI, 0.08942‐0.4486). These data showed that the combination of HOTTIP, PVT1, and UCA1 as a predictive panel, has a better diagnostic performance than each of these lncRNAs individually, and could be used for the screening of patients with advanced CRC.