Shotaro Fujita

Prognostic role of FUT8 expression in relation to p53 status in stage II and III colorectal cancer

The expression of fucosyltransferase 8, an enzyme responsible for core fucosylation encoded by FUT8, influences tumor biology and correlates with patient prognosis in several solid cancers. We hypothesized that p53 alteration modifies prognostic associations of FUT8 expression in colorectal cancer (CRC), since FUT8 has recently been identified as a direct transcriptional target of wild-type p53. Utilizing multiple datasets of microarray and RNA sequence of CRC, FUT8 mRNA was found to be highly expressed in wild-type p53 tumors (n = 382) compared to those of mutant p53 (n = 437). Prognostic values of FUT8 expression in conjunction with the p53 status for disease-free survival (DFS) were analyzed using two independent cohorts of stage II and III CRC after curative surgery, including the immunohistochemistry (IHC) cohort (n = 123) and the microarray cohort (n = 357). In both cohorts, neither FUT8 expression nor the p53 status was associated with DFS. Strikingly, positive expression of FUT8 protein was significantly associated with better DFS only in tumors with negative p53, while it had no prognostic impact in tumors with positive p53 in the IHC cohort. Although not statistically significant, a similar prognostic trend was observed in the microarray cohort when patients were stratified by the p53 status. Our results suggest that the prognostic values of FUT8 expression on DFS may be modified by the p53 status, and the expression of FUT8 protein can be a prognostic biomarker for patients with stage II and III CRC.

Prognostic impact of preoperative lymphocyte-to-monocyte ratio in patients with colorectal cancer with special reference to myeloid-derived suppressor cells

AIMS We aimed to investigate the relationship of colorectal cancer prognosis and inflammatory parameters, including neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR), with reference to circulating myeloid-derived suppressor cells (MDSCs) in the current study. PATIENTS AND METHODS Thirty-five patients who underwent curative-intent surgery were enrolled.　A receiver-operating characteristic curve (ROC) was used to assess the usefulness of candidates for prognostic factors. Recurrence-free survival (RFS) was calculated using the Kaplan-Meier method, and the candidates for prognostic factors were assessed by a Cox proportional hazard model. RESULTS ROC curve analyses determined cutoff values for NLR and LMR as 2.9 and 2.4, respectively. The percentage of MDSCs in patients with LMR ≤ 2.4 was statistically higher than in those with LMR > 2.4 (p = 0.012). The patients with LMR ≤ 2.4 exhibited a statistically lower RFS than those with LMR > 2.4 (p = 0.008). These results were also observed in patients with stage II + III disease. LMR was an independent prognostic factor of RFS in colorectal cancer patients (hazard ratio: 7.757, 95% confidence interval: 1.462-41.152, p = 0.016). CONCLUSION Lower LMR was associated with poor prognosis in colorectal cancer patients; whereas, higher circulating MDSCs were observed in patients with lower LMR.