Claudin-4 Expression is Associated with Survival in Ovarian Cancer but Not with Chemotherapy Response

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title = "Claudin-4 Expression is Associated with Survival in Ovarian Cancer but Not with Chemotherapy Response",
abstract = "The tight junction protein claudin-4 has been reported to be overexpressed in advanced ovarian cancer. We investigated the prognostic significance of claudin-4 overexpression and whether claudin-4 expression could predict platinum response in primary ovarian carcinoma (OC). Claudin-4 expression was evaluated by immunohistochemistry in a tissue microarray of 140 OCs. Multivariable Cox-regression models were used to assess the effect of claudin-4 overexpression on progression-free survival and overall survival (OS). Kaplan-Meier survival analyses and the logrank test were performed comparing claudin-4 high and low groups. The association between claudin-4 expression and platinum resistance was assessed using risk ratios and the Pearson χ 2 test. A dataset of >1500 epithelial ovarian cancers was used to study the association between CLDN4 mRNA and survival. Of 140 evaluable cases, 71 (51{\%}) displayed high claudin-4 expression. Claudin-4 overexpression predicted shorter 5-yr progression-free survival and OS in univariable analyses [hazard ratio (HR)=1.6 (1.1-2.5), P=0.020 and HR=1.6 (1.0-2.4), P=0.041, respectively]. Hazard of relapse was similar [HR=1.5 (1.0-2.4)] after adjustment for age, stage, type, and BRCA1/2 status in a multivariable analysis, but the evidence was slightly weaker (P=0.076). Validation in an external cohort confirmed the association between high expression of CLDN4 and poor 10-yr OS [HR=1.3 (1.1-1.5), P<0.001]. However, no confident association between claudin-4 and platinum sensitivity was found in our cohort [risk ratio=1.2 (0.7-2.0), P=0.3]. These findings suggest that high expression of claudin-4 may have a prognostic value in OC. The role of claudin-4 in the development of platinum resistance remains unclear.",
keywords = "Claudin-4, Ovarian carcinoma, Platinum resistance, Prognostic factor",
author = "{Mart{\'i}n De La Fuente}, Laura and Susanne Malander and Linda Hartman and J{\"o}nsson, {Jenny Maria} and Anna Ebbesson and Mef Nilbert and Anna M{\aa}sb{\"a}ck and Ingrid Hedenfalk",
year = "2018",
doi = "10.1097/PGP.0000000000000394",
language = "English",
volume = "37",
pages = "101--109",
journal = "International Journal of Gynecological Pathology",
issn = "0277-1691",
publisher = "Lippincott Williams and Wilkins",
number = "2",