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

Kobayashi, Takashi; Honda, Kazufumi

doi:10.1080/14737159.2019.1643718

Cited by 6 publications

(8 citation statements)

References 30 publications

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“…Screening the general population for PC is not advisable, because the overall lifetime risk of developing PC is relatively low (approximately 1%). Indeed, PC screening does not meet some of the criteria set by the World Health Organization [ 4 , 23 ]. Information about the accuracy, acceptability, cost and availability of screening tests for PC, and agreement on who should be treated on the basis of the results of such tests are required.…”

Section: Discussionmentioning

confidence: 99%

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

Sato

Kobayashi

Nishiumi

et al. 2020

Cancers

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Apolipoprotein A2-ATQ/AT (apoA2-ATQ/AT) has been identified as a minimally invasive biomarker for detecting pancreatic cancer (PC) and high-risk (HR) individuals for PC. To establish an efficient enrichment strategy for HR, we carried out a plasma apoA2-ATQ/AT level-based prospective screening study among the general population. The subjects for the screening study were recruited at six medical check-up facilities in Japan between October 2015 and January 2017. We evaluated the positive predictive value (PPV) of the plasma apoA2-ATQ/AT level of ≤35 μg/mL for detecting PC and HR. Furthermore, we prospectively confirmed its diagnostic accuracy with another post-diagnosis population in a cross-sectional study. We enrolled 5120 subjects in experimental screening, with 84 subjects (1.3%) showing positive results for apoA2-ATQ/AT. Pancreatic abnormalities were recognized in 26 of the 84 subjects from imaging examinations. Pancreatic abnormalities detected included 1 PC and 15 HR abnormalities, such as cystic lesions including intraductal papillary mucinous neoplasm. The PPV of apoA2-ATQ/AT for detecting PC and HR was 33.3%. Moreover, a combination study with another cross-sectional study revealed that the area under the curve for apoA2-ATQ/AT to distinguish PC from healthy controls was 0.903. ApoA2-ATQ/AT has the potential to enrich PC and HR by increasing the diagnostic probability before imaging examinations.

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Section: Discussionmentioning

confidence: 99%

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

Sato

Kobayashi

Nishiumi

et al. 2020

Cancers

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“…-ATQ/-ATQ Autoimmune pancreatitis ↑ protein expression [56] Seemingly healthy subjects [59] Autoimmune pancreatitis ↓ protein expression [56] T2D ↑ degree of oxidation [61] Seemingly healthy subjects [59] -ATQ/-AT Autoimmune pancreatitis chronic pancreatitis; pancreatic cancer ↓ protein expression [59] T2D ↑ degree of oxidation [61] Seemingly healthy subjects [56,57,59]…”

Section: Isoform Associated Pathology Effect Of Amino Acid Change Ref...mentioning

confidence: 99%

“…ApoA-II has a major isoform with pI 5 and several minor isoforms that are either more basic or more acidic than the major isoform [ 39 ]. The five circulating apoA-II dimeric isoforms are -ATQ/-ATQ (apoA-II-1, 17.380 Da), -ATQ/-AT (apoA-II-2, 17.252 Da), -AT/-AT (apoA-II-3, 17.124 Da), -AT/-A (apoA-II-4, 17.023 Da), and -A/-A (apoA-II-5, 16.922 Da), and they are identified both in healthy individuals and in individuals with various pathologies [ 56 , 57 , 58 , 59 , 60 ] ( Table 2 ). For example, -ATQ/-AT isoform has a low level of expression in patients with autoimmune pancreatitis, chronic pancreatitis, or pancreatic cancer [ 56 , 57 , 59 ], while -ATQ/-ATQ isoform has an elevated level in patients with autoimmune pancreatitis [ 56 ].…”

Section: Apoa-ii Expression and Structural-functional Propertiesmentioning

confidence: 99%

Apolipoprotein A-II, a Player in Multiple Processes and Diseases

et al. 2022

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Apolipoprotein A-II (apoA-II) is the second most abundant apolipoprotein in high-density lipoprotein (HDL) particles, playing an important role in lipid metabolism. Human and murine apoA-II proteins have dissimilar properties, partially because human apoA-II is dimeric whereas the murine homolog is a monomer, suggesting that the role of apoA-II may be quite different in humans and mice. As a component of HDL, apoA-II influences lipid metabolism, being directly or indirectly involved in vascular diseases. Clinical and epidemiological studies resulted in conflicting findings regarding the proatherogenic or atheroprotective role of apoA-II. Human apoA-II deficiency has little influence on lipoprotein levels with no obvious clinical consequences, while murine apoA-II deficiency causes HDL deficit in mice. In humans, an increased plasma apoA-II concentration causes hypertriglyceridemia and lowers HDL levels. This dyslipidemia leads to glucose intolerance, and the ensuing high blood glucose enhances apoA-II transcription, generating a vicious circle that may cause type 2 diabetes (T2D). ApoA-II is also used as a biomarker in various diseases, such as pancreatic cancer. Herein, we provide a review of the most recent findings regarding the roles of apoA-II and its functions in various physiological processes and disease states, such as cardiovascular disease, cancer, amyloidosis, hepatitis, insulin resistance, obesity, and T2D.

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“…In the last two decades, we identified unique alterations of processing patterns in C-terminal amino acids of circulating apoA2-homodimer [apoA2-isoforms (apoA2-i)] in patients with pancreatic cancer and in HRIs, and we have continued to develop efficient screening methods for pancreatic cancer with a blood test for apoA2-i [ 6 , 11 , 12 ]. The possibility of developing efficient pancreatic cancer screening with the apoA2-i blood test is reviewed in this report.…”

Section: Introductionmentioning

confidence: 99%

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

Honda

2022

CBM

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Though pancreatic cancer is uncommon, with an age-adjusted annual incidence of 12.9 cases per 100,000 person-years, it is considered a refractory cancer due to the mortality of 11.0 per 100,000 person-years. To efficiently identify patients with potentially surgically-curable pancreatic cancer, high-risk individuals (HRIs) for pancreatic cancer should be identified by easily and minimally invasive methods from the general population. We have identified unique processing patterns in the C-terminal amino acids of apolipoprotein A2 homodimer in the blood of patients with pancreatic cancer and in HRIs, and we called them apoA2-isoforms (apoA2-i). We then established an enzyme-linked immunosorbent assay (ELISA) to measure circulating apoA2-i in the blood stream. The diagnostic accuracy of apoA2-i to distinguish pancreatic cancer HRIs was verified by several retrospective studies, blind testing with the National Cancer Institute (NCI) Early Detection Research Network (EDRN), a prospective study with prediagnostic samples organized by the European Prospective Investigation into Cancer and Nutrition (EPIC) study, and the prospective screening study of pancreatic cancer in Kobe. The apoA2-i blood test is a potential biomarker to identify HRIs and the curative stage of pancreatic cancer in the general population.

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

Cited by 6 publications

References 30 publications

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

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

Apolipoprotein A-II, a Player in Multiple Processes and Diseases

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

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