Abstract

<div>Abstract<p><b>Background:</b> Germline genetic variants in <i>PLCE1</i> (10q23) have demonstrated consistent associations with risk of esophageal squamous cell carcinoma (ESCC) and gastric cancer among Chinese. We evaluated PLCE1 mRNA and protein expression in paired tumor-normal tissues, and their relationship with survival.</p><p><b>Methods:</b><i>PLCE1</i> mRNA was profiled using three probes in the Affymetrix GeneChip U133 for paired tumor-normal tissues of ESCC (<i>n</i> = 132), gastric cardia adenocarcinoma (GCA, <i>n</i> = 62), and gastric noncardia adenocarcinoma (GNCA, <i>n</i> = 72). We used immunohistochemistry to detect PLCE1 protein on slides from tissue microarrays in paired tumor-normal tissues of ESCC (<i>n</i> = 303), and tumors of GCA (<i>n</i> = 298) and GNCA (<i>n</i> = 124).</p><p><b>Results:</b> Compared with normal tissues, <i>PLCE1</i> mRNA expression was significantly reduced in ESCC tumors (<i>P</i> = 0.03, probe_205112_at), as well as in GCA and GNCA tumors (<i>P</i> < 0.0001, each probe). Protein expression was nonsignificantly reduced in ESCC tumors (<i>P</i> = 0.51). Increased tumor-normal mRNA fold change (probe_205112_at) was associated with longer survival in ESCC (9.6 months for highest vs. lowest quartile; <i>P</i><sub>trend</sub> = 0.02). Increased mRNA tumor-normal fold change (probe_205111_at) was associated with longer survival for GCA (10.7 months for highest quartile; <i>P</i><sub>trend</sub> = 0.04), but not for GNCA cases (<i>P</i> = 0.72). Similar to mRNA, elevated tumor-normal fold change for protein in ESCC was also associated with improved survival (8.1 months for highest quartile; <i>P</i><sub>trend</sub> = 0.04).</p><p><b>Conclusions:</b> Dysregulated PLCE1 mRNA expression was observed for both ESCC (one probe only) and GCA tumors, and the altered PLCE1 expression seems to be associated with cancer prognosis.</p><p><b>Impact:</b> A potential role for PLCE1 in the early detection and/or therapy of ESCC and GCA warrants further investigation. <i>Cancer Epidemiol Biomarkers Prev; 23(8); 1579–88. ©2014 AACR</i>.</p></div>

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