Potential usefulness of apolipoprotein A2 isoforms for screening and risk stratification of pancreatic cancer

Abstract

Given the low incidence of pancreatic cancer in the general population, screening of pancreatic cancer in the general population using invasive modalities is not feasible. Combination of invasive screening with noninvasive biomarkers for pancreatic cancer and its precancerous lesions has the potential to reduce mortality due to pancreatic cancer. In this review, we focus on biomarkers found in the blood that can indicate early-stage pancreatic cancer, and we discuss current strategies for screening for pancreatic cancer. We recently identified a unique alteration in apolipoprotein A2 isoforms in pancreatic cancer and its precancerous lesions, and we describe its clinical usefulness as a potential biomarker for the early detection and risk stratification of pancreatic cancer.

Keywords: NCI EDRN; National Cancer Institute Early Detection Research Network; apolipoprotein A2 isoforms; early detection for pancreatic cancer; plasma/serum biomarker.

Figure 1.. Amino acid sequences of the apolipoprotein A2 isoforms [36].

Apolipoprotein AII is comprised of 77 amino acids and forms a homodimer in humans via a disulfide bond involving Cys6. The theoretical molecular weights of the five isoforms of apolipoprotein A2 are shown at left [36].

Figure 2.. Unique processing patterns of the C-terminal ends of the apoA2 homodimer in pancreatic ductal adenocarcinoma and precancerous lesions of PDAC.

(A) Normal, hypo-processing and hyper-processing patterns; and (B) representative gel-mobility image of MS spectra. (A) The normal type of apoA2 isoforms were mainly distributed in healthy controls. However, the hypo-processing pattern, in which apoA2-ATQ/ATQ was predominantly expressed, and the hyper-processing pattern, in which apoA2-AT/AT was predominantly expressed were detected in PDAC or its risk diseases. In both the hyper- and hypo-processing patterns, because apoA2-ATQ/ATQ or apoA2-AT/AT was increased, apoA2-ATQ/AT consequently decreased in PDAC [36]. (B) MALDI-MS spectra were converted to gel-mobility images (16,500–17,500 m/z). The expression patterns were different in each case. Top blue: healthy controls; top red: PDAC; bottom green: normal pattern; bottom purple: hypo-processing pattern; bottom brown: hyper-processing pattern [36]. MS: Mass spectrometry; PDAC: Pancreatic ductal adenocarcinoma.

Figure 3.. ROC and AUC values of apoA2-ATQ/AT and CA19–9.

2D scatter graph of apoA2-ATQ/ATQ and apoA2-AT/AT in the multi-institutions study. (A & B) ROC curves and AUC values of apoA2 and CA19–9 to distinguish patients with PDAC from healthy controls. The patients with PDAC were classified into clinical stages according to the Union for International Cancer Control (red line, stage I; green line, stage II, orange line, stage III and purple line, stage IV) [36].(C & D) 2D scatter graphs of apoA2-ATQ/ATQ (y-axis) and apoA2-AT/AT (x-axis) in PDAC (orange letter Xs) versus healthy controls (blue circles) (C) and diseases of the pancreas other than PDAC (orange letter Xs) versus healthy controls (blue circles) (D). The representative hyper- or hypo-processing pattern was recognized in PDAC and risk diseases of pancreatic cancer [ 36]. PDAC: Pancreatic ductal adenocarcinoma; ROC: Receiver-operating characteristic.