Clinical Significance of Plasma Apolipoprotein-AII Isoforms as a Marker of Pancreatic Exocrine Disorder for Patients with Pancreatic Adenocarcinoma Undergoing Chemoradiotherapy, Paying Attention to Pancreatic Morphological Changes

Abstract

Background. Circulating apolipoprotein-AII (apoAII-) ATQ/AT is a potential useful biomarker for early stage pancreatic ductal adenocarcinoma (PDAC), but its clinical significance in PDAC patients remains uncertain. The aim of the current study was to assess the usefulness of apoAII-ATQ/AT as a surrogate for the effect of chemoradiotherapy (CRT) and its association with pancreatic exocrine disorder, paying attention to morphological changes of the pancreas. Methods. In the 264 PDAC patients who were enrolled in our CRT protocol, the following parameters were measured at specified time points before and after CRT: serum levels of albumin, total cholesterol, and amylase as indices of pancreatic exocrine function, serum levels of CA19-9, and the pancreatic morphology including tumor size (TS), main pancreatic duct diameter (MPDD), and pancreatic parenchymal volume excluding tumor volume (PPV) by using computed tomography (CT) images. Plasma apoAII-ATQ/AT levels were simultaneously measured with enzyme-linked immunosorbent assay in 4 healthy volunteers and the 44 PDAC patients before and after CRT. Plasma apoAII-ATQ/AT levels after CRT were analyzed according to small/large-MPDD and small/large-PPV groups based on their median values after CRT. Plasma samples after CRT were measured after incubation with human pancreatic juice (PJ) to examine the relevance between apoAII isoforms and circulating pancreatic enzymes. Results. The serum levels of albumin, amylase, CA19-9, TS, MPDD, and PPV after CRT were significantly lower than those before CRT (median, before vs. after: 3.9 g/dl, 74 U/l, 180.2 U/ml, 58.1 mm, 4.0 mm, and 34.8 ml vs. 3.8, 59, 43.5, 55.6, 3.6, and 25.2). ApoAII-ATQ/AT levels (median, μg/ml) of PDAC patients before CRT were significantly lower than those in healthy volunteers: 32.9 vs. 61.2, and unexpectedly those after CRT significantly decreased: 14.7. The reduction rate of apoAII-ATQ/AT was not correlated with those of CA19-9 and TS, indicating that apoAII-ATQ/AT is not a tumor-specific marker. On the other hand, the patient group with large MPDD and small PV exhibited higher apoAII-ATQ levels than those with small MPDD and large PPV. The incubation of plasma samples after CRT with PJ did not alter apoAII-ATQ/AT and apoAII-AT levels but significantly decreased apoAII-ATQ levels, suggesting that circulating pancreatic enzymes markedly influenced apoAII-ATQ levels. Conclusions. ApoAII-ATQ/AT levels are not useful for evaluation of clinical effect of CRT for PDAC, but apoAII isoforms are very useful to assess pancreatic exocrine disorder because pancreatic atrophy and insufficient secretion of circulating pancreatic enzymes are considered likely to influence apoAII-ATQ levels.

Prospective Study Using Plasma Apolipoprotein A2-Isoforms to Screen for High-Risk Status of Pancreatic Cancer

“…These processing patterns might be useful for distinguishing PC from CP or AIP, and might also be key to elucidating why the plasma apoA2-ATQ/AT level is useful as a biomarker of PC [ 26 ]. Hayasaki et al [ 27 ] recently reported that pancreatic atrophy and insufficient secretion of circulating pancreatic enzymes might influence apoA2-ATQ levels, and suggested that apoA2-ATQ levels could offer a useful biomarker for assessing pancreatic exocrine disorders. As a hypothesis, this abnormal hyper-processing of the C-terminal end of the apoA2 homodimer was anticipated to be caused by the activity of circulating pancreatic enzymes due to minor pancreatitis with pancreatic cancer or other pancreatic disorders, and the abnormal hypo-processing pattern was presumed to occur by reducing the circulating pancreatic enzymes due to pancreatic atrophy and insufficiency.…”

Trends in biomarker discoveries for the early detection and risk stratification of pancreatic cancer using omics studies

“…Although the mechanisms underlying these findings are still unknown, we have previously reported that specific abnormal processing patterns of amino acid in the C-terminal ends of apoA2 homodimer were observed in PDAC or autoimmune pancreatitis (AIP) [27,28]. Hayasaki et al recently reported that apoA2-ATQ levels seem to reflect pancreatic atrophy and insufficient secretion of circulating pancreatic enzymes, and could provide a biomarker to assess pancreatic exocrine disorder [29].…”

Risk stratification of pancreatic cancer by a blood test for apolipoprotein A2-isoforms

“…Thus, a hypo-processing pattern of apoA2-i is a unique finding in AIP, and a significant decrease of apoA2-AT/AT may be associated with the reduction of the exocrine function of the pancreas that occurs in AIP. In addition, Hayasaki et al identified that apoA2-ATQ/ATQ was significantly increased in patients who underwent radiation for pancreatic cancer with neoadjuvant therapy before surgery, in comparison with the patients before undergoing radiation therapy [ 18 ]. This finding is also consistent with the reduction of the exocrine function of the pancreas with exposure to radiation.…”