Observational Study
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World J Gastroenterol. Dec 14, 2014; 20(46): 17532-17540
Published online Dec 14, 2014. doi: 10.3748/wjg.v20.i46.17532
Plasma cathepsin L: A prognostic marker for pancreatic cancer
Nidhi Singh, Prasenjit Das, Surabhi Gupta, Vikas Sachdev, Siddhartha Srivasatava, Siddhartha Datta Gupta, Ravindra Mohan Pandey, Peush Sahni, Shyam S Chauhan, Anoop Saraya
Nidhi Singh, Surabhi Gupta, Vikas Sachdev, Siddhartha Srivasatava, Anoop Saraya, Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi 110029, India
Prasenjit Das, Siddhartha Datta Gupta, Deparment of Pathology, All India Institute of Medical Sciences, New Delhi 110029, India
Ravindra Mohan Pandey, Department of Biostatistics, All India Institute of Medical Sciences, New Delhi 110029, India
Peush Sahni, Department of GI Surgery, All India Institute of Medical Sciences, New Delhi 110029, India
Shyam S Chauhan, Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, 110029, India
Author contributions: Singh N, Pandey RM, Sahni P, Chauhan SS and Saraya A designed the research; Singh N and Das P performed the research; Singh N, Sachdeva V, Srivastava S and Sahni P contributed new reagents/analytic tools; Singh N, Das P, Gupta S, Datta Gupta S, Pandey RM, Chauhan SS and Saraya A analyzed the data; and Singh N, Das P, Gupta S, Datta Gupta S, Chauhan SS and Saraya A wrote the paper.
Supported by Grants from Indian Council of Medical Research, New Delhi and Council of Scientific and Industrial Research, New Delhi
Correspondence to: Anoop Saraya, Professor, Department of Gastroenterology and Human Nutrition, 3rd Floor, Teaching Block, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India. ansaraya@yahoo.com
Telephone: +91-11-26593359 Fax: +91-11-26588663
Received: February 11, 2014
Revised: May 12, 2014
Accepted: July 15, 2014
Published online: December 14, 2014
Processing time: 310 Days and 14.6 Hours
Abstract

AIM: To assess the prognostic significance of cathepsin L, a cysteine protease that degrades the peri-tumoral tissue, in patients with pancreatic cancer.

METHODS: Plasma samples from 127 pancreatic cancer patients were analyzed for cathepsin L levels by ELISA. Out of these patients, 25 underwent surgery and their paraffin-embedded tissue was analyzed for cathepsin L expression by immunohistochemistry. Survival of patients and clinicopathological parameters was correlated with cathepsin L expression in plasma and tissue using appropriate statistical analysis.

RESULTS: The mean (± SD) cathepsin L in plasma samples of pancreatic cancer patients was 5.98 ± 2.5 ng/mL that was significantly higher compared to the levels in healthy controls (3.83 ± 0.45) or chronic pancreatitis patients (3.97 ± 1.06). Using ROC curve, a cut-off level of 5.0 ng/mL was decided for survival analysis. Elevated plasma levels of cathepsin L were found to be associated with poor prognosis (P = 0.01) in multivariate analysis. The plasma levels of the protease decreased after surgery. Though no significant correlation was seen between plasma and tissue expression of this protease, a trend did emerge that high cathepsin L expression in tissue correlated with its high levels in plasma.

CONCLUSION: Cathepsin L levels in plasma of pancreatic cancer patients may be used as a potential prognostic marker for the disease.

Keywords: Cathepsin L; Pancreatic cancer; Overall median survival; Plasma

Core tip: Cathepsin L is a lysosomal cysteine protease, which degrades extracellular matrix during cancer cell invasion. It has been shown to have prognostic value in pancreatic tumor tissue. But blood based markers can be more useful. Elevated levels of cathepsin L in plasma have been reported but no study has exhibited prognostic significance of cathepsin L levels in blood. This study for the first time reported that elevated levels of cathepsin L in plasma predict poor prognosis in pancreatic cancer and these levels decrease after surgery.