Sporadic colorectal cancer: Studying ways to an end

Abstract

Introduction: Although colorectal cancer (CRC) has often been regarded as a single entity, different pathways may lead to macroscopically similar cancers. These pathways may evolve into a patchy colonic field defect that we aimed to study in consecutive CRC patients. Methods: In a single-center, observational, prospective study, consecutive CRC patients were included if surgery and a perioperative colonoscopy were planned. Personal and familial history data were collected. Tumors were studied for microsatellite instability (MSI) status, DNA repair protein expression (DRPE) and presence of BRAF and/or APC mutations.Macroscopically normal mucosa samples were tested for APC mutations. Presence and location of synchronous and metachronous adenomas and patient follow-up were analyzed. The association of two categorical variables was tested through the Fisher's exact test (SPSS 19). Results: Twenty-four patients (12 male, mean age 69 years) were studied. High-grade MSI (MSI-H) was found in eight tumors-these were significantly more common in the right colon (p ¼ 0.047) and more likely to have an altered DRPE (p ¼ 0.007). BRAF mutation was found in two of six tested MSI-H tumors. APC gene mutations were found in nine of 16 non-MSI-H tumors and absent in normal mucosa samples. There was a nonsignificant co-localization of CRC and synchronous adenomas and a significant co-localization (p ¼ 0.05) of synchronous and metachronous adenomas. Discussion: Sporadic CRCs evolve through distinct pathways, evidenced only by pathological and molecular analysis, but clinically relevant both for patients and their families. In non-MSI-H tumors, the expected APC gene mutations were not detected by the most commonly used techniques in a high number of cases. More studies are needed to fully characterize these tumors and to search for common early events in normal mucosa patches, which might explain the indirect evidence found here for a field defect in the colon.

Comprehensive analysis of expression profiles of long non‑coding RNAs with associated ceRNA�network involved in gastric cancer progression

“…PART1 expression has also been shown to be markedly decreased in the glioma tissues compared with normal brain tissues and its low expression was negatively associated with overall patient survival (42,43). PART1 is located in chromosome 5q, which is deleted in prostate cancer patients and cell lines and potentially contains cancer suppressor genes for prostate cancer, suggesting its crucial role in inhibiting prostate carcinogenesis (44,45). The downregulation of PART1 has been shown to inhibit the cell proliferation of prostate cancer and to promote cell apoptosis by modulating the Toll-like receptor pathway (46).…”