Long non-coding RNA C20orf56 as a predictor of response to neoadjuvant CCRT and survival rates of rectal cancers

Colorectal cancer is the third most prevalent malignancy and the second leading cause of cancer mortality worldwide. Neoadjuvant concurrent chemoradiotherapy (CCRT) improves survival and increases curative surgery rates in rectal cancer. C20orf56, a long non-coding RNA (lncRNA), plays diverse roles in cancer, but its association with neoadjuvant CCRT response and prognosis in rectal cancer remains unexplored.

Tumor samples from 343 rectal cancer patients who received neoadjuvant CCRT followed by surgery were analyzed for C20orf56 expression via in situ hybridization. Associations between C20orf56 expression and clinicopathological parameters were evaluated with the χ² test. Survival outcomes were assessed using the Kaplan-Meier method and compared by log-rank tests, while multivariate analysis was conducted using a Cox proportional hazards model. Additionally, an independent cohort of responders and non-responders (n=8 per group) was used to validate C20orf56 transcript levels by real-time RT-PCR.

A transcriptomic analysis (GSE35452) identified C20orf56 as differentially expressed between responders and non-responders. Decreased expression of C20orf56 showed significant correlations with less advanced post-treatment tumor invasiveness, negative post-treatment nodal metastasis, absence of vascular invasion and perineural invasion, and improved response to neoadjuvant CCRT (all p≤0.024). Diminished expression of C20orf56 was associated not only with favorable disease-specific survival (DSS), local recurrence-free survival (LRFS), and metastasis-free survival (MeFS) (all p<0.0001) in univariate analysis but also functioned as an independent predictor signifying enhanced clinical outcomes, including DSS, LRFS, and MeFS (all p<0.001). In the real-time RT-PCR analysis, the transcriptomic levels were significantly lower in the responder group compared with the non-responder group (p=0.007).

C20orf56 may play a significant role in rectal cancer progression and response to neoadjuvant CCRT, serving as a novel prognostic factor.