Assessment of circulating microRNA specific for patients with familial adenomatous polyposis.

Circulating microRNAs (miRNAs) are considered promising biomarkers for diagnosis, prognosis, and treatment efficacy of diseases. However, usefulness of circulating miRNAs as biomarkers for hereditary gastrointestinal diseases have not been confirmed yet. We explored circulating miRNAs specific for patients with familial adenomatous polyposis (FAP) as a representative hereditary gastrointestinal disease. Next-generation sequencing (NGS) indicated that plasma miR-143-3p, miR-183-5p, and miR-885-5p were candidate biomarkers for five FAP patients compared to three healthy donors due to moderate copy number and significant difference. MiR-16-5p was considered as an internal control due to minimum difference in expression across FAP patients and healthy donors. Validation studies by real-time PCR showed that mean ratios of maximum expression and minimum expression were 2.2 for miR-143-3p/miR-16-5p, 3.4 for miR-143-3p/miR-103a-3p, 5.1 for miR-183-5p/miR-16-5p, and 4.9 for miR-885-5p/miR-16-5p by using the samples collected at different time points of eight FAP patients. MiR-143-3p/16-5p was further assessed using specimens from 16 FAP patients and 7 healthy donors. MiR-143-3p was upregulated in FAP patients compared to healthy donors (P = 0.04), but not significantly influenced by clinicopathological features. However, miR-143-3p expression in colonic tumors was rare for upregulation, although there was a significant difference by existence of desmoid tumors. MiR-143-3p transfection significantly inhibited colorectal cancer cell proliferation compared to control microRNA transfection. Our data suggested regulation of miR-143-3p expression differed by samples (plasma or colonic tumors) in most FAP patients. Upregulation of plasma miR-143-3p expression may be helpful for diagnosis of FAP, although suppressive effect on tumorigenesis seemed insufficient in FAP patients.

Combination of preoperative tumour markers and lymphovascular invasion with TNM staging as a cost and labour efficient subtyping of colorectal cancer.

Tumour-Node-Metastasis (TNM) staging of colorectal cancer (CRC) needs further classification for better treatment because of disease heterogeneity. Although molecular classifications which are expensive and laborious are under study, cost and labour efficient subtyping is desirable. We assessed the combinations of preoperative tumour marker (TM) elevation and tumour lymphovascular invasion (LVI) as a solution. We used the pooled data of 7151 colon cancer (CC) patients and 4620 rectal cancer (RC) patients who received curative surgery between 2004 and 2008 in Japan. The best-matched subtyping for predicting relapse-free survival (RFS) was statistically selected using the c-index and Akaike's information criterion. This subtyping (TM-LVI), which consisted of three categories by TM elevation status and severity of LVI status, was an independent prognostic factor for RFS of CC (stage IIa, IIIb, and IIIc) and RC (stage I, IIa, IIb, IIIa, and IIIb) and also for disease specific survival of CC (stage IIa, IIb, IIIb, and IIIc) and RC (all stage except for IIc). Although TM-LVI classified CRC patients into low and high recurrence risk groups, the application of adjuvant therapy was not accordance with the TM-LVI status. TM-LVI may be a cost and labour efficient subtyping of colorectal cancer for better treatment strategy.