RIPK3 expression as a potential predictive and prognostic marker in metastatic colon cancer

Colorectal cancer is one of the primary causes of cancer-related deaths and 5-fluorouracil (5-FU) therapy remains the cornerstone of treatment in these patients. Resistance to 5-FU represents a major obstacle; therefore, finding new predictive and prognostic markers is crucial for improvement of pat...

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Published in:	Clinical and investigative medicine Vol. 42; no. 1; pp. E31 - E38
Main Authors:	Conev, Nikolay V, Dimitrova, Eleonora G, Bogdanova, Margarita K, Kashlov, Yavor K, Chaushev, Borislav G, Radanova, Maria A, Petrov, Dilyan P, Georgiev, Kaloyan D, Bachvarov, Chavdar H, Todorov, George N, Kalchev, Kalin P, Popov, Hristo B, Manev, Rostislav R, Donev, Ivan S
Format:	Journal Article
Language:	English
Published:	Canada Canadian Society for Clinical Investigation 23-03-2019
Subjects:	Apoptosis Apoptosis - drug effects Biomarkers Cancer therapies Chemotherapy Clinical outcomes Colonic Neoplasms - genetics Colonic Neoplasms - metabolism Colonic Neoplasms - pathology Colorectal cancer Colorectal Neoplasms - genetics Colorectal Neoplasms - metabolism Female Fluorouracil - pharmacology Humans Kinases Male Medical prognosis Metastasis Patients Prognosis Proteins Receptor-Interacting Protein Serine-Threonine Kinases - genetics Receptor-Interacting Protein Serine-Threonine Kinases - metabolism Retrospective Studies Stains & staining Systematic review Tomography Tumor necrosis factor-TNF Tumors
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Summary:	Colorectal cancer is one of the primary causes of cancer-related deaths and 5-fluorouracil (5-FU) therapy remains the cornerstone of treatment in these patients. Resistance to 5-FU represents a major obstacle; therefore, finding new predictive and prognostic markers is crucial for improvement of patient outcomes. Recently a new type of programmed cell death was discovered-necroptosis, which depends on receptor interacting protein 3 (RIPK3). Preclinical data showed that necroptotic cell death is an important effector mechanism of 5-FU-mediated anticancer activity. To investigate the predictive and prognostic performance of RIPK3 expression in primary tumors. Colon cancer patients (n=74) with metastatic stage were included in this retrospective study and all were treated with first-line 5-FU based chemotherapy. Immunohistochemical staining was performed. The progression free survival for the low expression group of RIPK3 was 5.6 months (95% CI, 4.4-6.8) vs 8.4 months (95% CI, 6.4-10.3) of the group with high expression (p=0.02). Moreover, patients with high expression of RIPK3 were associated with lower risk of disease progression HR 0.61 (95% CI, 0.38-0.97; p=0.044). Patients with high expression levels of RIPK3 also had significantly longer mean overall survival (OS) of 29.3 months (95% CI, 20.8-37.8) as compared with those with low expression: 18.5 months (95% CI, 15.06-21.9) (p= 0.036). In addition, univariate analysis showed that high level of RIPK3 expression was associated with a longer OS HR 0.59 (95% CI, 0.35-0.98; p=0.044). This study suggests that expression of RIPK3 in primary tumors of metastatic colon cancer patients should be further investigated for its potential as a promising predictive and prognostic marker.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1488-2353 1488-2353
DOI:	10.25011/cim.v42i1.32390