Circulating proteins and risk of pancreatic cancer: a case-subcohort study among Chinese adults

Abstract

Background Pancreatic cancer has a very poor prognosis. Biomarkers that may help predict or diagnose pancreatic cancer may lead to earlier diagnosis and improved survival. Methods The prospective China Kadoorie Biobank (CKB) recruited 512 891 adults aged 30–79 years during 2004–08, recording 702 incident cases of pancreatic cancer during 9 years of follow-up. We conducted a case-subcohort study measuring 92 proteins in 610 cases and a subcohort of 623 individuals, using the OLINK immuno-oncology panel in stored baseline plasma samples. Cox regression with the Prentice pseudo-partial likelihood was used to estimate adjusted hazard ratios (HRs) for risk of pancreatic cancer by protein levels. Results Among 1233 individuals (including 610 cases), several chemokines, interleukins, growth factors and membrane proteins were associated with risk of pancreatic cancer, with adjusted HRs per 1 standard deviation (SD) of 0.86 to 1.86, including monocyte chemotactic protein 3 (MCP3/CCL7) {1.29 [95% CI (confidence interval) (1.10, 1.51)]}, angiopoietin-2 (ANGPT2) [1.27 (1.10, 1.48)], interleukin-18 (IL18) [1.24 (1.07, 1.43)] and interleukin-6 (IL6) [1.21 (1.06, 1.38)]. Associations between some proteins [e.g. matrix metalloproteinase-7 (MMP7), hepatocyte growth factor (HGF) and tumour necrosis factor receptor superfamily member 9 [TNFRSF9)] and risk of pancreatic cancer were time-varying, with higher levels associated with higher short-term risk. Within the first year, the discriminatory ability of a model with known risk factors (age, age squared, sex, region, smoking, alcohol, education, diabetes and family history of cancer) was increased when several proteins were incorporated (weighted C-statistic changed from 0.85 to 0.99; P for difference = 4.5 × 10–5), although only a small increase in discrimination (0.77 to 0.79, P = 0.04) was achieved for long-term risk. Conclusions Several plasma proteins were associated with subsequent diagnosis of pancreatic cancer. The potential clinical utility of these biomarkers warrants further investigation.

Circulating Protein Biomarkers for Prognostic Use in Patients with Advanced Pancreatic Ductal Adenocarcinoma Undergoing Chemotherapy

“…The main strength of our study is the inclusion of a relatively large number of patients with advanced PDAC, and the Olink PEA method used. Today, >800 articles have described this method, including more than 120 studies of patients with cancer, but only four studies of patients with PDAC [23,24,43,44]. With results from 737 samples from 363 patients, we confirmed IL-6 as a prognostic marker in PDAC; moreover, we described other proteins that had previously been reported in relation to PDAC to also have prognostic capabilities.…”

Deciphering the action mechanism of paeoniflorin in suppressing pancreatic cancer: A network pharmacology study and experimental validation

“…By activating MAPK pathways, RAS oncogenes may play a crucial role in the constitutive production of MMP1 in human pancreatic cancer cells ( Huang et al, 2018 , 1). MMP7 is involved in the injury response of mucosal epithelia and the degradation of extracellular matrix components, and it has been shown to be overexpressed in pancreatic ductal adenocarcinoma and its precursors, PanIN and intraductal papillary mucinous neoplasms, with MMP7 alterations evident even in intermediate-grade ( Kartsonaki et al, 2022 ). IL-17 stimulates MMP7 expression in prostate cancer to destroy the E-cadherin/β-catenin complex and release -catenin, hence promoting EMT and tumor cell invasion ( Zhang et al, 2017 ).…”

Clinical applications of plasma proteomics and peptidomics: Towards precision medicine

“…Using these platforms, researchers can detect more than 3000 protein markers from as little as 8 μl plasma or other body fluids, laying the foundation for proteomics‐driven precision medicine [6]. It has already been used for a number of cancers and COVID‐19 clinical studies [104–110]. An alternative approach is a combination of technologies to increase overall performance.…”

“…Typically, for the MS-based discovery and clinical translation of plasma biomarkers, a "pyramid strategy" is adopted, which first analyses a small number of samples as deeply as pos- Using these platforms, researchers can detect more than 3000 protein markers from as little as 8 μl plasma or other body fluids, laying the foundation for proteomics-driven precision medicine [6]. It has already been used for a number of cancers and COVID-19 clinical studies [104][105][106][107][108][109][110]. An alternative approach is a combination of technologies to increase overall performance.…”