A Retrospective Study in Colorectal Adenocarcinoma Uncovers the Potential of Circ-CCT3 as a Predictor of Tumor...

Background/Objectives: Colorectal cancer (CRC) is one of the most prevalent malignancies; this issue underlines the need for accurate molecular biomarkers for early detection and accurate prognosis. Circular RNAs (circRNAs) have recently emerged as very promising cancer biomarkers. The circular transcript of the chaperonin-containing TCP1 subunit 3 (CCT3) gene, namely circ-CCT3, is a significant oncogenic driver. In gastrointestinal malignancies, circ-CCT3 promotes tumor growth by sponging tumor-suppressor miRNAs. In this study, we examined whether circ-CCT3 expression can predict the prognosis of patients diagnosed with colorectal adenocarcinoma, the most frequent type of CRC. Methods: Total RNA was extracted from pulverized, fresh frozen colorectal tissues and reverse-transcribed. A previously developed, highly sensitive quantitative PCR (qPCR) assay was applied to determine circ-CCT3 expression in 216 primary colorectal adenocarcinoma tissue specimens and 86 paired normal colorectal tissues. Results: circ-CCT3 was significantly upregulated in colorectal adenocarcinoma tissues, in comparison to their non-cancerous tissue counterparts. Higher circ-CCT3 expression was associated with a poorer disease-free (DFS) and overall survival (OS) of colorectal adenocarcinoma patients. Interestingly, multivariate Cox regression showed that the prognostic value of circ-CCT3 expression regarding DFS was independent of other established prognosticators used in clinical practice, including TNM staging. Furthermore, the stratification of patients based on the TNM classification of the tumors revealed that increased circ-CCT3 levels predicted shorter DFS and OS intervals, especially in the subgroup of TNM stage II or III patients. Conclusions: Our study provides evidence that circ-CCT3 overexpression constitutes a promising molecular biomarker of poor prognosis in colorectal adenocarcinoma, independently predicting tumor recurrence.