Down-regulation of hK7 in the sera of breast cancer and benign breast disease patients
HELIYON
Authors: Ejaz, Samina; Nasim, Faiz-ul-Hassan; Ashraf, Muhammad; Ahmad, Gulzar
Abstract
Introduction: Breast cancer is known as a leading cause of cancer-related death among women all over the world. Biomarkers facilitate diagnosis at the earliest possible stage and better prognosis of the disease. Hence, may help to improve the overall survival rate among breast cancer patients. To find a better diagnostic/prognostic marker we evaluated human tissue kallikrein 7 (hK7) as biomarker of breast cancer. hK7 is a secreted serine protease having chymotrypsin like activity. Serum hK7 is known to have aberrant expression in ovarian and prostate cancer but has not been yet studied in breast cancer. However, the expression level of KLK7 mRNA in breast cancer tissues has been indicated as a better prognostic marker for the unfavorable prognosis of breast carcinoma. Materials and methods: In this study a time-resolved immunofluorometric indirect back titration ELISA (bt-ELISA) was employed for the quantification of hK7 in serum of breast cancer patients (n = 47), benign breast disease patients (n = 13) alongwith the gender and age group specific controls (n = 99). Results: hK7 was significantly down-regulated in the sera of female breast cancer patients (p < 0.0001; Mean 0.704 +/- 0.533 mu g/L) and benign breast disease patients (p = 0.0008; Mean 0.651 +/- 0.584) as compared to normal controls (Mean 1.665 +/- 1.174 mu g/L). Conclusions: Down regulation of hK7 suggests the possible role of this protein in natural course of breast cancer and benign breast diseases. Study should be
Prognostic significance of multiple kallikreins in high-grade astrocytoma
BMC CANCER
Authors: Drucker, Kristen L.; Gianinni, Caterina; Decker, Paul A.; Diamandis, Eleftherios P.; Scarisbrick, Isobel A.
Abstract
Background: Kallikreins have clinical value as prognostic markers in a subset of malignancies examined to date, including kallikrein 3 (prostate specific antigen) in prostate cancer. We previously demonstrated that kallikrein 6 is expressed at higher levels in grade IV compared to grade III astrocytoma and is associated with reduced survival of GBM patients. Methods: In this study we determined KLK1, KLK6, KLK7, KLK8, KLK9 and KLK10 protein expression in two independent tissue microarrays containing 60 grade IV and 8 grade III astrocytoma samples. Scores for staining intensity, percent of tumor stained and immunoreactivity scores (IR, product of intensity and percent) were determined and analyzed for correlation with patient survival. Results: Grade IV glioma was associated with higher levels of kallikrein-immunostaining compared to grade III specimens. Univariable Cox proportional hazards regression analysis demonstrated that elevated KLK6-or KLK7-IR was associated with poor patient prognosis. In addition, an increased percent of tumor immunoreactive for KLK6 or KLK9 was associated with decreased survival in grade IV patients. Kaplan-Meier survival analysis indicated that patients with KLK6-IR < 10, KLK6 percent tumor core stained < 3, or KLK7-IR < 9 had a significantly improved survival. Multivariable analysis indicated that the significance of these parameters was maintained even after adjusting for gender and performance score. Conclusions: These data suggest that elevations in glioblastoma KLK6, KLK7 and KLK9 protein have utility as prognostic markers of patient survival.