Clinical Significance of Human Kallikrein Gene 6 Messenger RNA Expression in Colorectal Cancer

Abstract

Purpose: Human kallikrein gene 6 (KLK6) is a member of the human kallikrein gene family, and recent studies have found that many kallikreins have altered expression patterns in various malignancies.The purpose of the current study was to quantify the expressionof KLK6 inmalignant and benign colorectal tissues and to statistically analyze whether KLK6 expression levels correlate with clinicopathologic variables and prognosis in patients with colorectal cancer. Experimental Designs: Paired colorectal tissue samples from cancerous and corresponding noncancerous tissues were obtained from 63 patients with colorectal cancer who underwent surgical resection. Quantitative analyses of KLK6 mRNA expression were done using real-time quantitative reverse transcription-PCR. Results: KLK6 mRNA overexpression in cancerous tissues compared with normal counterparts was observed in 57 of 63 (90%) patients.The mean expression level of KLK6 mRNA in cancerous tissues was significantly higher than that in noncancerous tissues (P < 0.0001). Elevated KLK6 expression was significantly correlated with serosal invasion (P < 0.05), liver metastasis (P < 0.05), and advanced Duke's stage (P < 0.01). Furthermore, patients with high KLK6 expression had a significantly poorer actuarial overall survival than patients with low KLK6 expression (5-year overall survival rates: 54% and 73%, respectively, P < 0.05). Conclusions:The results of this study indicated that KLK6 mRNA expression was significantly higher in cancerous than in noncancerous colorectal tissues, and high expression of KLK6 mRNA correlated with serosal invasion, liver metastasis, advanced Duke's stage, and a poor prognosis for patients with colorectal cancer.

Kallikrein 6 is a mediator of K-RAS-dependent migration of colon carcinoma cells

“…Patients with ovarian carcinoma also had significantly higher levels of serum KLK6, about twice the concentration of normal or benign tumor patients (Diamandis et al, 2003). In both gastric and colon cancer, KLK6 mRNA was observed to be more highly expressed as compared to normal mucosa Ogawa et al, 2005). In each previously mentioned study, above average expression of KLK6 correlated with a poor prognosis (Diamandis et al, 2003;Nagahara et al, 2005;Ogawa et al, 2005;Santin et al, 2005).…”

Kallikrein-Related Peptidase 14 Acts on Proteinase-Activated Receptor 2 to Induce Signaling Pathway in Colon Cancer Cells

“…Nevertheless, using a multivariate statistical analysis, elevated KLK14 levels were found to be associated with an unfavorable survival prognosis in patients with colon cancer. 36 Other studies using an in silico analysis 19 and real-time PCR quantification [37][38][39] did not report differences in KLK14 expression between colonic tumors and their paired normal mucosa. This discrepancy in KLK14 expression between previously published data and the present findings are most likely due to specimen selection and to differences in the KLK14 detection methods used (eg, in silico, quantitative RT-PCR, and ELISA rather than IHC analysis).…”

Fatty Acid Binding Protein 6 Is Overexpressed in Colorectal Cancer

“…The following primers were used to amplify genes: FABP6 (sense primer, 5 ¶-ACTACTCCGGGGGCCACACCAT-3 ¶ and antisense primer, 5 ¶-GTCTCTTGCTCACGCGCTCATAGG-3 ¶) and GAPDH (sense primer, 5 ¶-TTGGTATCGTGGAAGGACTCA-3 ¶ and antisense primer, 5 ¶-TGTCAT-CATATTTGGCAGGTTT-3 ¶). The reaction was done in a LightCycler system (Roche Applied Science, Indianapolis, IN) using the LightCyclerFastStart DNA Master SYBR Green I kit (Roche Applied Science) as described previously (7). In brief, thermal cycling for all genes was initiated with a denaturation step of 95jC for 10 minutes, followed by 40 cycles at 95jC for 10 seconds, 64jC (60jC for GAPDH) for 10 seconds, and 72jC for each optimal length (s/25 bp).…”