Involvement of Kallikrein-Related Peptidases in Normal and Pathologic Processes

Table 1

Kallikrein-related peptidases. Gene expression pattern, SNPs, and promoter methylation related to cancer and other diseases. CSF = cerebrospinal fluid.

Disease	Kallikrein	Factor	Observation	Reference
Alzheimer’s disease	KLKs 6 (CSF), 10	Increased expression		[39–42]
	KLKs 6 (brain, blood), 7	Decreased expression
Amelogenesis imperfecta	KLK4	Mutation	Disease-causing mutation	[43–45]
Aneurism	KLK6	Decreased expression	Suggestion of unfavorable prognosis	[46, 47]
	KLK8	SNP	Suggestion of unfavorable prognosis
Asthma	KLK3	SNP		[48]
Atopic dermatitis	KLK5	Decreased expression		[49, 50]
Bipolar disease	KLK8	SNP	Suggestion of unfavorable prognosis	[51]
Coronary artery disease	KLK1	SNP	Controversial prognosis	[52, 53]
	KLK1	Increased expression	Predictor of disease
Kidney disease
Lupus nephritis	KLK1	SNP	Disease-associated SNP
Acute kidney injury	KLK1	SNP	Suggestion of unfavorable prognosis	[54–56]
Diabetic nephropathy	KLK1	Increased expression	Tubular inflammation
Multiple sclerosis	KLK6	Increased expression	Advanced disease	[57–59]
Dementia with Lewy bodies	KLK6	Decreased expression	Suggestion of diagnostic marker	[60]
Other neurodegenerative diseases	KLKs 1, 5, 6, 7, and 9	Increased expression	Suggestion of disease-associated marker	[61–63]
Other skin diseases	KLKs 5–8, 10–13, and 15	Increased expression	Suggestion of unfavorable prognosis	[64–73]
Netherton syndrome	KLK5	Increased expression	Suggestion of unfavorable prognosis
Psoriasis	KLK8	Increased expression	Suggestion of unfavorable prognosis	[74, 75]
	KLKs 6, 8, 10, and 13	Increased expression	Severity of skin lesions
Parkinson’s disease	KLK6	Increased expression	Disease-associated marker	[76]
Sjogren disease	KLK11	Increased expression	Suggestion of disease-associated marker	[77]
Breast cancer	KLKs 2, 4	SNP	Breast cancer risk
	KLK3	SNP	Association with less aggressiveness
	KLKs 5, 10, and 14	Increased expression	Potential diagnostic biomarkers
	KLKs 6, 12 variant 3, and 15	Increased expression	Suggestion of favorable prognosis	[4, 47, 78–83]
	KLKs 3, 8, and 12	Decreased expression	Suggestion of favorable prognosis
	KLKs 5, 7	Increased expression	Suggestion of unfavorable prognosis
	KLK10	Methylation	Suggestion of favorable prognosis
Cervix cancer	KLK7	Increased expression	Controversial prognosis	[84, 85]
Colorectal cancer	KLKs 4, 6, 7, and 10	Increased expression	Suggestion of unfavorable prognosis	[86–90]
Gastric cancer	KLKs 6, 7, and 10	Increased expression	Suggestion of unfavorable prognosis
	KLK13	Increased expression	Suggestion of favorable prognosis	[90–95]
	KLK11	Decreased expression	Suggestion of unfavorable prognosis
Head and neck cancer	KLK10	Methylation	Suggestion of unfavorable prognosis	[96–99]
	KLKs 4–8, 10	Increased expression	Suggestion of unfavorable prognosis
Intracranial tumor	KLKs 6–8	Increased expression	Controversial prognosis	[100, 101]
Lung cancer	KLK10	Methylation		[102–106]
	KLKs 5–7	Increased expression	Suggestion of unfavorable prognosis
	KLKs 11, 13, and 14	Increased expression	Diagnostic marker
	KLKs 8, 12	Decreased expression	Suggestion of unfavorable prognosis
Melanoma	KLKs 6, 8, and 13	Increased expression		[107, 108]
	KLK7	Increased expression	Suggestion of favorable prognosis
Ovarian cancer	KLKs 4, 6	Increased expression	Advanced stage
	KLKs 8–10, 11, 13, and 14	Increased expression	Suggestion of favorable prognosis
	KLKs 5, 7	Increased expression	Suggestion of unfavorable prognosis	[47, 78, 109–125]
	KLK10, KLKP1	SNP
	KLKs 3, 15	SNP	Suggestion of unfavorable prognosis
Pancreatic cancer	KLK7	Increased expression	Controversial prognosis	[126]
Prostate cancer	KLK3	Increased expression	Disease monitoring and recurrent prediction	[47, 78, 127–147]
	KLKs 1, 2, 4, and 15	Increased expression
	KLKP1	Decreased expression
	KLK7	Increased expression	Controversial prognosis
	KLK11	Decreased expression	Suggestion of unfavorable prognosis
	KLKs 2, 3, 4, and 10	SNP	Suggestion of unfavorable prognosis
	KLK12	SNP	Cancer predisposition
	KLKs 4, 14, and 15	SNP	Suggestion of unfavorable prognosis