Lysosomal Cathepsins B and L and Stef in A Blood Levels in Patients with Hepatocellular Carcinoma and/or Liver Cirrhosis: Potential Clinical Implications

Abstract

The serum levels of lysosomal cathepsin B and L and Stefin A, an intracellular inhibitor of these proteolytic enzymes, were determined in patients with hepatocellular carcinoma (HCC) and/or liver cirrhosis (LC) and correlated with some clinical and biochemical parameters of these diseases. Cathepsin B serum levels were increased in HCC and in LC patients as compared to normal subjects (p < 0.001). However no difference was observed between HCC and LC groups. Interestingly, a significant relationship was evidenced between cathepsin B serum content and the grade of severity of cirrhosis (r = 0.41; p < 0.001). Cathepsin L was significantly elevated only in sera of cancer patients as compared to normal subjects or LC patients (p < 0.001) and significantly correlated with the number of malignant lesions (r = 0.49; p = 0.001). Stefin A serum levels were increased in HCC and LC patients as compared to healthy subjects (p < 0.02). However, these levels were significantly higher in the LC group as compared to the HCC group (p < 0.05). In cancer patients, a significant relationship was observed between Stefin A serum content and tumor size (r = 0.35; p < 0.05), number of neoplastic lesions (r = 0.556; p < 0.001) and serum a-fetoprotein (r = 0.38; p < 0.01). These data suggest that cathepsin B and L and Stefin A may be potentially useful as additional biochemical parameters to monitor the therapeutic response of these diseases to clinical treatments and to identify patients with cirrhosis developing precancerous lesions.

Identification of Cystatin B as a Potential Serum Marker in Hepatocellular Carcinoma

“…However, the cystatin A serum levels were significantly higher in liver cirrhosis patients than in the HCC patients. The cystatin A serum levels correlated with the tumor size, number of neoplastic lesions, and serum AFP level in HCC patients (29). This study found that the serum CSTB levels seemed to increase according to the stepwise progression of liver disease (i.e., from chronic hepatitis to HCC).…”

“…AGC1 is the major proteoglycan of the cartilage extracellular matrix and seems to be involved in the fibrogenic process in rat (28). The serum levels of the cysteine proteinase inhibitor cystatins as well as lysosomal proteases cathepsins have been reported to be higher in patients with various types of tumors (29,30). However, the levels of CSTB in HCC have not been determined yet.…”

Gene expression profile of DNA binding protein A transgenic mice

“…CTSL (cathepsin L) is significantly elevated in the sera of cancer patients as compared to normal subjects or liver cirrhosis patients and correlates with the number of malignant lesions (27).…”

Subcloning and Expression of Functional Human Cathepsin B and K in E. coli: Characterization and Inhibition by Flavonoids

“…and have been linked to many types of cancer including melanoma (Matarrese et al, 2010;Quintanilla-Dieck et al, 2008), hepatocellular carcinoma (Leto et al, 1997;Leto et al, 1996), breast cancer (Foekens et al, 1998;Laurent-Matha et al, 1998;Masson et al, 2011;Vashishta et al, 2007), lung cancer (Ledakis et al, 1996;Schweiger et al, 2000), prostate cancer (Brubaker et al, 2003;Kishore Kumar et al, 2010;Podgorski et al, 2009;Podgorski et al, 2007;Steffan et al, 2010), nasopharyngeal cancer (Cheng et al, 2008;Xu et al, 2009), thyroid cancer (Mikosch et al, 2008;Tedelind et al, 2010), bone cancer Podgorski et al, 2007) as well as osteoporosis (Bone et al, 2010;Deal, 2009;Stoch and Wagner, 2007;Yasuda et al, 2005), rheumatoid arthritis (Skoumal et al, 2005;Skoumal et al, 2008), Alzheimer's Disease (Hook et al, 2007;Hook et al, 2009;Urbanelli et al, 2008), cardiovascular disease (Bengtsson et al, 2008;Lutgens et al, 2007), and obesity (Li et al, 2010;Naour et al, 2010;Podgorski et al, 2007;Yang et al, 2008).…”