The role of Cathepsin S as a marker of prognosis and predictor of chemotherapy benefit in adjuvant CRC: a pilot study

Gormley, Julie A.; Hegarty, Shauna; O’Grady, Anthony; Stevenson, Michael R.; Burden, Roberta E.; Barrett, Helen L.; Scott, Christopher J.; Johnston, James A.; Wilson, Robert H.; Kay, Elaine W.; Johnston, Patrick G.; Olwill, Shane A.

doi:10.1038/bjc.2011.408

Cited by 60 publications

(48 citation statements)

References 45 publications

(57 reference statements)

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“…Immunohistochemical scoring of cathepsin S in these samples revealed expression in more than 95% of the samples, with a 1.3-fold increase in cathepsin S in tumours vs. normal tissues. Survival analysis also revealed a correlation between survival and cathepsin S expression, with high cathepsin S expression being indicative of poorer prognosis (Gormley et al, 2011).…”

Section: Cathepsin S As a Diagnostic/ Prognostic Markermentioning

confidence: 99%

Cathepsin S: therapeutic, diagnostic, and prognostic potential

Wilkinson

Williams

Scott

et al. 2015

Biological Chemistry

161

137

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Cathepsin S is a member of the cysteine cathepsin protease family. It is a lysosomal protease which can promote degradation of damaged or unwanted proteins in the endo-lysosomal pathway. Additionally, it has more specific roles such as MHC class II antigen presentation, where it is important in the degradation of the invariant chain. Unsurprisingly, mis-regulation has implicated cathepsin S in a variety of pathological processes including arthritis, cancer, and cardiovascular disease, where it becomes secreted and can act on extracellular substrates. In comparison to many other cysteine cathepsin family members, cathepsin S has uniquely restricted tissue expression and is more stable at a neutral pH, which supports its involvement and importance in localised disease microenvironments. In this review, we examine the known involvement of cathepsin S in disease, particularly with respect to recent work indicating its role in mediating pain, diabetes, and cystic fibrosis. We provide an overview of current literature with regards cathepsin S as a therapeutic target, as well as its role and potential as a predictive diagnostic and/or prognostic marker in these diseases.

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Section: Cathepsin S As a Diagnostic/ Prognostic Markermentioning

confidence: 99%

Cathepsin S: therapeutic, diagnostic, and prognostic potential

Wilkinson

Williams

Scott

et al. 2015

Biological Chemistry

161

137

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“…Expression associated with reduced recurrence-free survival after surgery alone, and improved response to 5-FU therapy 175 Bax BAX Pro-apoptotic protein that facilitates cytochrome c release Expression associated with improved 5 y survival, 176 though also reduced response to irinotecan chemotherapy 176 MMP matrix metalloproteinase, TIMP tissue inhibitor of metalloproteinase, ROS reactive oxygen species, 5-FU 5-fluorouracil, MnSOD manganese superoxide dismutase, CD44 cluster of differentiation 44, TGF-b tumor growth factor b, PCNA proliferating cell nuclear antigen, 5-FU 5-fluorouracil…”

Section: Genome-wide Association Studies: Expanding On Heritable Riskmentioning

confidence: 97%

Prognostic and Predictive Biomarkers in Colorectal Cancer: Implications for the Clinical Surgeon

2015

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Colorectal cancer is a heterogeneous disease with a wide range of long-term outcomes and responses to treatment. Recent advances in the genetic and molecular characterization of tumors has yielded a set of prognostic and predictive biomarkers that aid the identification of patients at higher risk for disease recurrence and progression, and in some cases indicate the likelihood of response to a specific treatment. Increasingly, these biomarkers have become integral to the treatment algorithm for managing patients with colorectal cancer. Prognostic and predictive factors in colorectal cancer can broadly be categorized into treatment impact, clinicopathologic factors, and molecular markers. This review will focus primarily on molecular markers, which are foundational to the paradigmatic shift toward personalized cancer therapy.

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“…For this reason, other biomarkers and genetic predictors, such as p21, p53, Bax, Bcl2, COX2, VEGF, EGFR and thymidylate synthase [41][42][43], have been studied. Some newly predictive biomarkers are also reported, including Cathepsin S [44], expression of CD133 [45], methylation of long interspersed nuclear element-1(LINE-1) [46], and GRP78 the 78-kDa glucose-regulated protein [47], but some of them are contradictory. These new biomarkers may help predict which patients may respond, but they could not directly translate into widely and low-cost clinical use.…”

Section: Discussionmentioning

confidence: 99%