Human kallikrein-related peptidase 12 (KLK12) splice variants expression in breast cancer and their clinical impact

Abstract

Kallikrein-related peptidases (KLKs) are a group of 15 serine proteases, hormonally regulated, and localized on chromosome 19q13.4. Alternative splicing is a process that plays significant role in the development, physiology, and different diseases, like cancer. Kallikrein family numbers more than 82 alternative transcripts. Understanding the role that those gene transcripts play in various cancer types, could lead to the discovery of diagnostic markers or drug targets. The present study was designed to analyze the expression profile of the splice variants of kallikrein-related peptidase 12 (KLK12) in breast cancer patients and to evaluate their clinical significance. KLK12 splice variants (KLK12sv3 and KLK12sv1/KLK12sv2) were examined in 69 tissue samples of breast cancer using quantitative real-time PCR as well as semi-quantitative PCR. Relative quantitative expression of KLK12 was statistically associated to clinicopathological parameters. From the splice variants examined, statistical associations with clinicopathological parameters were obtained only from KLK12sv3 variant. KLK12sv3 is more frequently expressed in tumors of lower grade (p = 0.040), early patient TNM stage (p = 0.024), and smaller tumor size (p = 0.023). Positive KLK12sv3 expression is associated with longer patient disease-free survival (DFS) (p = 0.042) and higher progesterone receptor concentration (p = 0.008). KLK12sv1/KLK12sv2 expression is statistically associated with KLK12sv3 expression (p = 0.001). KLK12sv3 can be regarded as a marker of good prognosis in breast cancer.

The diagnostic and prognostic value of serum human kallikrein-related peptidases 11 in non-small cell lung cancer

“…In contrast, KLK8 and KLK9 expression have been reported to be favorable prognosis in ovarian cancer [19,20]. In addition, KLK12 is reported to be an independent and favorable prognostic marker for breast cancer [21]. Sasaki et al [11] have indicated that there is a significant correlation between decreased KLK11 mRNA expression level and poor prognosis in lung cancer.…”

Transcriptome changes upon in vitro challenge with Mycobacterium bovis in monocyte-derived macrophages from bovine tuberculosis-infected and healthy cows

“…Since the probe sequences were quite different, the KLK family may also participate in long-term infection. KLK12 and KLK11 are believed to have diverse functions and may be used as biomarkers for certain kinds of cancers (Lose et al, 2011;Talieri et al, 2012). Downregulated expression of the KLK family may be caused by high levels of tissue factor pathway inhibitor 2 (TFPI2) expression, encoding a serine proteinase inhibitor that may inhibit many serine proteases and plasma kallikrein.…”

KLK14 (kallikrein-related peptidase 14)

“…Note KLK12 mRNA expression is downregulated in breast cancer tissues and is upregulated by steroid hormones in breast and prostate cancer cell lines (Talieri et al, 2012;Yousef et al, 2000). Prognosis KLK12 variant 3 expression is downregulated in breast tumors of small size, high grade, and advanced TNM stage.…”

“…Prognosis KLK12 variant 3 expression is downregulated in breast tumors of small size, high grade, and advanced TNM stage. Moreover, KLK12 variant 3 overexpression is associated with superior diseasefree survival (DFS) rates for breast cancer patients, as well as with elevated progesterone receptor (PR) concentration (Talieri et al, 2012). (Zhao et al, 2012).…”