Abstract
PurposeThe aim of this study was to compare and contrast the expression of all members of the Kallikrein (KLK) family of genes across 15 cancer types and to evaluate their utility as diagnostic and prognostic biomarkers.ResultsSevere alterations were found in the expression of different Kallikrein genes across various cancers. Interestingly, renal clear cell and papillary carcinomas have similar kallikrein expression profiles, whereas, chromophobe renal cell carcinoma has a unique expression profile. Several KLK genes have excellent biomarker potential (AUC > 0.90) for chromophobe renal cell carcinoma (KLK2, KLK3, KLK4, KLK7, KLK15), renal papillary carcinoma (KLK1, KLK6, KLK7), clear cell renal cell carcinoma (KLK1, KLK6), thyroid carcinoma (KLK2, KLK4, KLK13, KLK15) and colon adenocarcinoma (KLK6, KLK7, KLK8, KLK10). Several KLK genes were significantly associated with mortality in clear cell renal cell carcinoma (KLK2: HR = 1.69; KLK4: HR = 1.63; KLK8: HR = 1.71; KLK10: HR = 2.12; KLK11: HR = 1.76; KLK14: HR = 1.86), papillary renal cell carcinoma (KLK6: HR = 3.38, KLK7: HR = 2.50), urothelial bladder carcinoma (KLK5: HR = 1.89, KLK6: HR = 1.71, KLK8: HR = 1.60), and hepatocellular carcinoma (KLK13: HR = 1.75).MethodsThe RNA-seq gene expression data were downloaded from The Cancer Genome Atlas (TCGA). Statistical analyses, including differential expression analysis, receiver operating characteristic curves and survival analysis (Cox proportional-hazards regression models) were performed.ConclusionsA comprehensive analysis revealed the changes in the expression of different KLK genes associated with specific cancers and highlighted their potential as a diagnostic and prognostic tool.
Highlights
The human kallikrein (KLK) gene family is the largest contiguous cluster of serine proteases within the human genome [1]
All fifteen members of the kallikrein family (KLK115) had their expression analyzed in fifteen different cancer types using the gene expression data from The Cancer Genome Atlas (TCGA)
Our analysis explored the expression of every member of the kallikrein family in 15 cancer types, yielding a comprehensive overview of KLK expression in these cancers
Summary
The human kallikrein (KLK) gene family is the largest contiguous cluster of serine proteases within the human genome [1]. The 15 members of the kallikrein gene family are located on chromosome 19q13.4 [2]. Members of the kallikrein family are often expressed in a tissue-specific manner and are regulated by transcriptional and post-transcriptional mechanisms such as steroid hormones (androgen response elements) and serpins, respectively [5,6,7,8]. Kallikreins are first secreted as zymogens in both intra and extracellular environments and are activated via other serine proteases or auto-activation [6, 9]. There is huge variability in the expression of each kallikrein in different tissue types throughout the body [5, 6, 10]
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