Molecular risk stratification of colorectal cancer can improve patient outcome. A panel of lncRNAs (H19, HOTTIP, HULC and MALAT1) derived from serum exosomes of patients with non-metastatic CRC and healthy donors was analyzed. Exosomes from healthy donors carried significantly more H19, HULC and HOTTIP transcripts in comparison to CRC patients. Correlation analysis between lncRNAs and clinical data revealed a statistical significance between low levels of exosomal HOTTIP and poor overall survival. This was confirmed by multivariate analysis that HOTTIP is an independent prognostic marker for overall survival (HR: 4.5, CI: 1.69-11.98, p = 0.0027). Here, HOTTIP poses to be a valid biomarker for patients with a CRC to predict post-surgical survival time.

Biomarkers may help predict the efficacy of neoadjuvant chemoradiation in patients with rectal cancer. We hypothesized that the expression of topoisomerase I (Topo I) and thymidylate synthase (TS) may help predict the treatment response in patients undergoing irinotecan and capecitabine-based chemoradiation. Patients with rectal cancer (cT3/4Nx or Tx/N+) received neoadjuvant chemoradiotherapy within clinical studies with irinotecan and capecitabine. Samples of normal and tumour tissues were collected before the start of the treatment and during surgical resection. Topo I and TS were measured using real-time PCR. The results of gene expression levels were compared between responders (defined as ypT0-2 ypN0) and nonresponders (ypT3-4 or ypN1/2). A total of 38 patients were analysed, 18 of them were responders. The biopsies of the untreated tumour tissue of responding patients showed a significant higher expression of Topo I compared with nonresponding patients (P = 0.015). Normal tissue did not show this difference (P = 0.126). During chemoradiation, the Topo I expression in tumour tissue of responders decreased significantly. TS did not show any differences between responders and nonresponders before treatment, but a significant decrease in the tumour tissue of responders was noted at the end of the treatment. Our data suggest that Topo I expression in rectal tumour mucosa might serve as a predictor of response to the neoadjuvant irinotecan-based chemoradiation, and hence might be a factor contributing to the development of individualized treatment.

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