Variable Levels of Long Noncoding RNA Expression in DNA Mismatch Repair-Proficient Early-Stage Colon Cancer

Abstract

Background: Long noncoding RNAs (lncRNAs) have been suggested to be biomarkers for diagnosis and prognosis of sporadic colorectal cancer.

Aims: This study aimed to characterize the expression profile of lncRNAs in DNA mismatch repair-proficient (pMMR) early-stage colon cancer (CC).

Methods: The microsatellite instability (MSI) status was examined by a multiplex PCR. The expression of lncRNA and mRNA was analyzed by microarrays. The differentially expressed lncRNAs and mRNAs were determined by bioinformatic analyses and validated in 44 CC samples and 32 non-tumor colonic specimens by quantitative real-time polymerase chain reaction (qRT-PCR).

Results: We found that 16 out of 67 CC had MSI-L CC and 7 with MSI-H. In comparison with that in five non-tumor colonic samples, microarray indicated that 1492 lncRNAs and 1639 mRNAs were upregulated while 1804 lncRNAs and 1073 mRNAs downregulated in four pMMR early-stage CC. Bioinformatic analyses revealed that the differentially expressed mRNAs were involved in the process of cell division, angiogenesis, apoptotic, differentiation, the PI3K-Akt/p53/TNF pathways and others. The co-expression lncRNA and mRNA networks indicated five hot spots with significantly high co-expression degrees. Further quantitative RT-PCR revealed that 4 out of 6 lncRNAs were significantly upregulated while the other 2 lncRNAs were downregulated in the CC. Stratification analysis demonstrated that 5 out of 6 lncRNAs were significantly associated with TNM stage and/or distant metastasis in this population.

Conclusion: Differentially expressed lncRNAs were significantly associated with clinical features of patients with pMMR CC and may participate in the tumorigenesis of pMMR CC.

Keywords: Colon cancer; LncRNA; MMR; Microarray.