Metastatic adenocarcinomas of left colon and rectum: differences in clinical outcome and gene expression

Background: There are relatively well-substantiated concepts regarding the differences in the clinical course of metastatic colorectal cancer depending on the primary tumor localization: right- and left-sided (including rectal). However, many clinical trials demonstrate clear differences in the selected efficacy of adjuvant chemotherapy in the treatment of rectal versus colon cancer. We hypothesize that there are significant differences in long-term outcomes between patients with metastatic rectal cancer (RC) and those with left-sided colon cancer (LSCC) that may depend on the genetic profile of the primary tumor. Methods: 155 patients with synchronous metastases of LSCC and 96 patients with RC were selected for clinical analysis. The TCGA database was used to obtain information on mRNA expression from the "Comprehensive molecular characterization of human colon and rectal cancer" study. 153 patients with LSCC and 41 patients with RC were included in this analysis. Results: Clinical analysis characterized by a significantly more favorable course of the disease after I and I+II lines of chemotherapy for RC group, which may be associated with a higher expression of EBI3, IL-17A, and SOCS1 in the primary tumor. Also, the RC group is characterized by a higher sensitivity to anti-VEGF therapy, which can be explained by a higher expression of VEGF-A, VEGF-D, and KDR-VEGFR2 compared to the LSCC group. Conclusion: Our study shows that when analyzing the effectiveness of antitumor therapy in patients with colorectal cancer, it is necessary to distinguish not only between groups with cancer of the right and left colon, but also to consider rectal cancer as a third independent group.