Serum apolipoprotein C-II is prognostic for survival after pancreatic resection for adenocarcinoma

Abstract

Background:Pancreaticoduodenectomy remains a major undertaking. A preoperative blood test, which could confidently predict the benefits of surgery would improve the selection of pancreatic cancer patients for surgery. This study aimed to identify protein biomarkers prognostic for long-term survival and to validate them with clinico-pathological information.Methods:Serum from 40 preoperative patients was used to train for predictive biomarkers using surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI), and the results were verified on 21 independent samples. Two predictive proteins were identified by tryptic peptide mass fingerprinting and sequencing, and validated on serum from another 57 patients by enzyme-linked immunosorbent assay (ELISA). The influence of these proteins on growth and invasion of two cancer cell lines was tested in-vitro.Results:The SELDI panel of m/z 3700, 8222 and 11 522 peaks predicted <12 months' survival (ROC AUC: 0.79, 0.64–0.90; P<0.039). When CA19-9 was added, the ROC AUC increased to 0.95 (0.84–0.99; P<0.0001). The six subjects in the verification group who died within 12 months were correctly classified. The m/z 8222 and 11 522 proteins were identified as Serum ApoC-II and SAA-1, respectively. In the validation samples, ELISA results confirmed that ApoC-II was predictive of survival (Kaplan–Meier P<0.009), but not SAA-I. ApoC-II, CA19-9 and major-vessel involvement independently predicted survival. ApoC-II and SAA-1 increased cell growth and invasion of both cancer cell lines.Conclusion:Serum ApoC-II, CA19-9 and major-vessel invasion independently predict survival and improves selection of patients for pancreaticoduodenectomy.

Potential prognostic significance of a new proteomic profile in patients with advanced pancreatic adenocarcinoma

“…Recent advances have shown that various proteomic values are proposed as prognostic factors for pancreatic adenocarcinoma; e.g., transthyretin [32], desmocollin 2 [33], Xb130 [34], heat shock protein 27 [35], extracellular high morbidity group box-1 [25], and apolipoprotein C-II [36]. In the current study, the seven-signal proteomic value showed unique characteristics compared with previously reported proteomics.…”

Apolipoproteins and cancer

“…47 Serum levels of APOC2 were elevated in pancreatic cancer patients compared to controls and had prognostic value for surgery. 48…”

miR‐4510 acts as a tumor suppressor in gastrointestinal stromal tumor by targeting APOC2

“…APOC2 acts as an important component of low‐density lipoproteins, very low‐density lipoproteins, and high‐density lipoproteins, where it assists to hydrolyze triglycerides associated with lipoproteins by activating lipoprotein lipase (LaRosa, Levy, Herbert, Lux, & Fredrickson, 1970). APOC2 has been demonstrated to be closely associated with survival of patients with pancreatic cancer (Xue et al, 2012). Elevated APOC2 promotes pancreatic cancer cell growth, migration, and invasion.…”

“…APOC2 has been demonstrated to be closely associated with survival of patients with pancreatic cancer (Xue et al, 2012). Elevated APOC2 promotes pancreatic cancer cell growth, migration, and invasion.…”