Neoadjuvant chemoradiotherapy (CRT) is one of the standards of care in locally advanced rectal cancer (LARC). This retrospective study examines clinical, analytical, and pathological parameters collected from 77 patients with locally advanced (cT3-4 or cN+) rectal carcinoma diagnosed between 2007 and 2017 at our institution that were treated with preoperative CRT and surgery. In the prognosis analysis, lower hemoglobin levels (p = 0.008), lower lymphocyte/monocyte ratio (LMR) (p = 0.011), and higher platelet/lymphocyte ratio (PLR) (p = 0.029) in the second determination (Hb2, LMR2 and PLR2) were associated with the relapse group. The number of positive nodes after surgery (N+) showed a statistically significant association with relapse (p = 0.012). KRAS mutations were associated with a worse prognosis for 5 years progression-free and overall survival (p = 0.005 and 0.022; respectively). We propose a prognostic model based on four parameters (number of positive lymph nodes after surgery, hemoglobin levels, LMR, and PLR after neoadjuvant therapy) that can be a useful tool to estimate relapse risk. Moreover, bilirubin could be a useful parameter to predict the response to neoadjuvant CRT.

Non-coding RNAs provide new opportunities to identify biomarkers that properly classify cancer patients. Here, we study the biomarker status of the mitochondrial long non-coding RNAs, MDL1 and MDL1AS. Expression of these genes was studied in public transcriptomic databases. In addition, a cohort of 69 locally advanced rectal cancer (LARC) patients with a follow-up of more than 5 years was used to determine the prognostic value of these markers. Furthermore, cell lines of colorectal (HCT116) and breast (MDA-MB-231) carcinoma were employed to study the effects of downregulating MDL1AS in vitro. Expression of MDL1AS (but not MDL1) was significantly different in tumor cells than in the surrounding tissue in a tumor-type-specific context. Both MDL1 and MDL1AS were accurate biomarkers for the 5-year survival of LARC patients (p = 0.040 and p = 0.007, respectively) with promising areas under the curve in the ROC analyses (0.820 and 0.930, respectively). MDL1AS downregulation reduced mitochondrial respiration in both cell lines. Furthermore, this downregulation produced a decrease in growth and migration on colorectal cells, but the reverse effects on breast cancer cells. In summary, MDL1 and MDL1AS can be used as reliable prognostic biomarkers of LARC, and MDL1AS expression provides relevant information on the diagnosis of different cancers.