lncRNA pair as candidate diagnostic signature for colorectal cancer based on the within-sample relative expression levels

Abstract

BackgroundEarly diagnosis of colorectal cancer could significantly improve the prognosis and reduce mortality. However, indeterminate diagnosis is often met in pathology diagnosis in biopsy samples. Abnormal expression of long non-coding RNA (lncRNA) is associated with the initiation and progression of colorectal cancer. It is of great value and clinical significance to explore lncRNAs as candidate diagnostic biomarkers in colorectal cancer.MethodsBased on the within-sample relative expression levels of lncRNA pairs, we identified a group of candidate diagnostic biomarkers for colorectal cancer. In addition, we validated it in independent datasets produced by different laboratories and different platforms. We also tested it in colorectal cancer tissue samples using quantitative real-time polymerase chain reaction (RT-qPCR).ResultsA biomarker consisting of six lncRNA pairs including nine lncRNAs was identified for the diagnosis of colorectal cancer. For a total of 950 cancer samples and 247 non-cancer samples, both of the sensitivity and specificity could achieve approximately 90%. For adenoma samples, the accuracy could achieve 73%. For normal tissues from inflammatory bowel disease patients, 93% (14/15) were correctly classified as non-cancer. Furthermore, the lncRNA pair biomarker showed excellent performance in all clinical stages; even in the early stage, the accuracy could achieve 87% and 82% in stage I and II. Meanwhile, the biomarker was also robust to the microsatellite instability status. More importantly, we measured the biomarker in 35 colorectal cancer and 30 cancer-adjacent tissue samples using quantitative real-time polymerase chain reaction (RT-qPCR). The accuracy could achieve 93.3% (70/75). Specially, even in early-stage tumors (I and II), the accuracy could also achieve 90.9% (30/33). The enrichment analysis revealed that these lncRNAs were involved in highly associated cancer pathways and immune-related pathways. Immune analysis showed that these marker lncRNAs were associated with multiple immune cells, implying that they might be involved in the regulation of immune cell functions in colorectal cancer. Most of the biomarker lncRNAs were also differentially expressed between the mutant group and wild-type group of colorectal cancer driver genes.ConclusionWe identified and validated six lncRNA pairs including nine lncRNAs as a biomarker for assisting in the diagnosis of colorectal cancer.