One of the limitations of this study is the

One of the limitations of this study is the differences in the patient populations between the two CRC patient cohorts. As shown in Table 1 and 2, there were differences in the number of patients with stage IV CRC between cohort 1 and cohort 2. At first, we validated the clinical significance of SNORA21 purchase FH535 in cohort 1 to determine the cut-off value of SNORA21 expression based on the comparison of cancerous and matched adjacent normal tissues. Since cohort 1 had a smaller population of patients with stage IV disease, we also validated the SNORA21 expression levels in cohort 2 by including 47 patients with stage IV CRC. In spite of the differences in the populations of two independent cohorts, SNORA21 expression consistently increased according to tumor invasion, distant metastasis and vascular invasion, indicating that SNORA21 may be involved in tumor progression.
Acknowledgements
Introduction Gastric cancer (GC) is the fourth most common human malignant disease and the second leading cause of cancer-related deaths worldwide. (Torre et al., 2015) In recent years, significantly improved outcomes have been reported for patients with GC, largely thanks to improved drug therapy. (Noh et al., 2014) According to new guidelines, 5-fluorouracil/oxaliplatin chemotherapy is recommended as the standard postoperative chemotherapy regimen for advanced GC. (Noh et al., 2014) Significant survival benefits of 5-fluorouracil/oxaliplatin chemotherapy have been reported in patients with metastatic gastric cancer as well as those who have undergone surgery. (Longley et al., 2003; McLean and El-Omar, 2014; Noh et al., 2014; Razzak, 2014) However, the efficacy of 5-fluorouracil/oxaliplatin chemotherapy greatly differs among individuals, with local recurrence or distant metastasis occurring in approxiamately 40% of GC patients during the course of the disease. (McLean and El-Omar, 2014; Razzak, 2014) Therefore, the accurate prediction of chemotherapy efficacy is clinically important to guide individualized regimens and improve treatment outcomes.(Jiang et al., 2016; McLean and El-Omar, 2014) Several potential molecular predictors (e.g., p53, cyclooxygenase 2 (COX2), p21, Ki-67, excision repair cross-complementing gene 1 (ERCC1), thymidylate synthase (TS), and thymidine phosphorylase (TP)) of chemosensitivity have been investigated in colon cancer, breast cancer and GC,(Kwon et al., 2007; Metzger et al., 1998; Sulzyc-Bielicka et al., 2011; Xu et al., 2016) but these biomarkers still require validation and are not a part of the standard clinical practice in GC evaluations. Therefore, prognostic and predictive tools are urgently required to identify those patients likely to benefit from 5-fluorouracil/oxaliplatin chemotherapy.(Longley et al., 2003). The PAKs (p21-activated kinases) belong to a highly conserved family of serine/threonine protein kinases that are important mediators of Rac and Cdc42 function.(Radu et al., 2014) PAKs have been implicated in the regulation of multiple cellular functions, including cell motility, actin reorganization, gene transcription, cell transformation, and apoptotic signaling, and more recently in radiotherapy and chemotherapy resistance signaling.(Radu et al., 2014; Zhang et al., 2010) PAK6 is the most recently identified and the least well known member of the PAK family. Recent studies have reported that PAK6 expression is increased and indicated poor prognosis in hepatocellular carcinoma (HCC), colorectal cancer (CRC) and prostate cancer (PCa).(Chen et al., 2015; Wen et al., 2009) Furthermore, PAK6 may be a good predictor of 5-FU response in colon cancer.(Chen et al., 2015) Knockdown of PAK6 expression inhibits PCa growth and enhances chemosensitivity to docetaxel (Wen et al., 2009). When combined with irradiation, inhibition of PAK6 leads to significantly decreased PCa cell survival.(Zhang et al., 2010) Another study reported that PAK6 expression was reduced and associated with good prognosis in clear cell renal cell carcinoma (ccRCC).(Liu et al., 2014) However, the molecular and prediction (prognosis and chemosensitivity) functions of PAK6 in GC are not yet well known.