Human Kallikrein 11 ELISA Kit

BACKGROUND: A relatively unexplored area for biomarker identification is alternative splice variants. We undertook this study to evaluate the usefulness of mRNA isoforms encoded by the KLK8 (kallikrein-related peptidase 8) gene as prognostic markers for lung cancer. METHODS: Real-time reverse-transcription PCR was used to analyze the mRNAs encoded by KLK8 (particularly 2 mRNA splice variants, KLK8-T3 and KLK8-T4) in 60 non-small-cell lung cancer (NSCLC) tumors and in paired unaffected tissues. The ratios of these mRNAs to those encoded by the KLK5, KLK6, KLK7, KLK10, KLK11, KLK13, and KLK14 genes were also determined and analyzed for correlations with various clinicopathologic variables. RESULTS: KLK8-T3 and KLK8-T4 were the most abundant of the 6 mRNA isoforms identified in lung tissues. The overall expression of the KLK8 gene and the amounts of the KLK8-T3 and KLK8-T4 mRNAs were significantly increased in lung tumor tissue (P < 0.0001). Univariate survival analysis revealed significant relationships of the relative concentrations of mRNA splice variants KLK8 (P = 0.043), KLK8-T3 (P = 0.037), and KLK8-T4 (P = 0.009) with overall survival (OS). Cox multivariate analysis indicated that the amount of KLK8-T4 mRNA was an independent prognostic factor for OS (relative risk = 3.90; P = 0.016) and that high KLK8-T4/KLK7, KLK8-T4/KLK10, and KLK8-T4/KLK11 mRNA ratios in NSCLC indicated increased risk of death. The increase was approximately 5-fold for the KLK8-T4/KLK7 and KLK8-T4/KLK10 ratios (P = 0.006, and P = 0.011, respectively) and 8-fold for the KLK8-T4/KLK11 ratio (P = 0.001). CONCLUSIONS: The KLK8-T4 alternative splice variant, alone or in combination, may be a new independent marker of unfavorable prognosis in lung cancer. (C) 2010 American Association for Clinical Chemistry

Several members of the KLK family have been proposed to modulate various tumor-relevant processes. Previously, we have shown that in advanced high-grade serous ovarian cancer tissue high KLK11 mRNA levels were significantly associated with prolonged overall and progression-free patients' survival. Furthermore, KLK11 mRNA expression positively correlated with KLK10 mRNA. In the present study, we examined the prognostic value for both KLK10 and KLK11 on the protein expression level by immunohistochemistry (IHC). A cohort encompassing 159 patient tumor samples afflicted with advanced high-grade (FIGO III/IV) serous ovarian cancer, present on tissue microarrays (TMA), was analyzed. For estimation of KLK10 and KLK11 immunoreactivity, an automated digital IHC image analysis algorithm was selected to quantify the antibody staining intensity in the tissues via an immunoreactive score (IRS). In line with the results obtained by mRNA analysis, KLK10 protein expression values were significantly and positively correlated with KLK11 protein expression values. In Kaplan-Meier analyses, both elevated KLK10, KLK11, and the combination of KLK10 and KLK11 protein levels were significantly linked with prolonged overall survival (OS). The addition of KLK10, KLK11 or the KLK10+KLK11 combination IRS to the base model in multivariate Cox analysis demonstrated that high KLK11 and KLK10+KLK11 protein expression levels, apart from clinical parameters, remained favorable independent predictive markers for OS. In conclusion, in the present study, we have validated the coordinate expression of KLK10 and KLK11 in advanced high-grade serous ovarian cancer. Furthermore, both increased KLK10 and KLK11 protein expression is associated with favorable prognosis in this major ovarian cancer subtype. The combined KLK10+ KLK11 marker performed even stronger than KLK10 or KLK11 alone.