Clinical impact of circulating LAPTM4B-35 in pancreatic ductal adenocarcinoma.

PURPOSE: LAPTM4B is upregulated in a wide range of cancers associated with poor prognosis. However, the clinical impact of LAPTM4B as diagnostic and prognostic marker in pancreatic ductal adenocarcinoma (PDAC) remains unknown. Thus, the aim of the present study was to investigate the expression of LAPTM4B as circulating marker in PDAC. METHODS: Expression analysis of LAPTM4B-35 in pancreatic tissue and preoperative blood serum samples of 169 patients with PDAC UICC Stages I-IV (n = 98), chronic pancreatitis (n = 41), and healthy controls (n = 30) by immunohistochemistry, Western blot, and ELISA. Descriptive and explorative statistical analyses of LAPTM4B-35's potential as diagnostic and prognostic marker in PDAC. RESULTS: Expression of LAPTM4B-35 was significantly increased in tumor tissue and corresponding blood serum samples of patients with PDAC (each p < 0.001) and it could well discriminate PDAC from healthy controls and chronic pancreatitis (p < 0.001; p = 0.0037). LAPTM4B-35 in combination with CA.19-9 outperforms the diagnostic accuracy with an AUC of 0.903 (p < 0.001), sensitivity of 82%, and specificity of 92%. Kaplan-Meier survival analysis revealed an improved overall survival in PDAC UICC I-IV with low expression of circulating LAPTM4B-35 (17 versus 10 months, p = 0.039) as well as an improved relapse-free survival in curatively treated PDAC UICC I-III (16 versus 10 months; p = 0.037). Multivariate overall and recurrence-free survival analyses identified LAPTM4B-35 as favorable prognostic factor in PDAC patients (HR 2.73, p = 0.021; HR 3.29, p = 0.003). CONCLUSION: LAPTM4B-35 is significantly deregulated in PDAC with high diagnostic and prognostic impact as circulating tumor marker.