High-density and targeted glycoproteomic profiling of serum proteins in pancreatic cancer and intraductal papillary mucinous neoplasm

Abstract

Objective: Glycoproteomics is an emerging subfield of proteomics. Tumor-specific variations in protein glycosylation might be potential targets for the development of new cancer diagnostics. Here, we performed high-throughput screening and targeted verification of glycome alterations in serum samples from patients with pancreatic cancer and the precancerous lesion intraductal papillary mucinous neoplasm (IPMN). Material and methods: The glycosylation profile of 1000 proteins was mapped in a discovery cohort comprising serum samples from 16 individuals, including 8 patients with pancreatic cancer and 8 healthy controls. The top 10 glycoprotein biomarker candidates with the highest signal intensity difference in glycosylation levels were evaluated in a cohort consisting of 109 serum samples, including 49 patients with resectable pancreatic cancer, 13 patients with resectable noninvasive IPMN and 47 healthy controls, using a targeted assay. Results: Multivariable analysis defined sets of panels comprising CA19-9 and distinctively glycosylated proteins for discrimination between pancreatic cancer, IPMN and healthy controls. A panel including CA 19-9, IL.17E, B7.1 and DR6 gave an AUC of 0.988 at 100% sensitivity at 90% specificity for the discrimination of stage 1 pancreatic cancer and healthy controls. B7.1 was found to be a valuable biomarker for differentiating between IPMN and healthy controls, with better performance alone than CA 19-9. Conclusions: Measurement of protein glycosylation profiles in serum may aid in the early detection of pancreatic cancer and precursor lesions.

The molecular, immune features, and risk score construction of intraductal papillary mucinous neoplasm patients

“…Aberrant glycosylation is a universal feature of cancer cells, and it is well established that even small changes to the glycome can severely affect tumor cell biology (Costa et al, 2020). Consistent with our research results, numerous studies have suggested that glycosylated proteins such as CEA (You et al, 2016), CA19-9 (Ciprani et al, 2020, B7.1 (Aronsson et al, 2018), and MUC7 (Carrara et al, 2011) are related to IPMN progression, therefore supporting the idea of glycosylated proteins as early diagnostic indicators of IPMN. Following this, the epithelial cell proliferation ability was markedly enhanced (IPMC stage), which was consistent with the morphological observations and confirmed in the stem cell score analysis.…”

“…In recent years, the detection rate of IPMN has been increasing with the advancement of medical imaging technologies, such as magnetic resonance imaging (MRI), computed tomography (CT), and endoscopic ultrasound (EUS) (Klibansky et al, 2012). Current IPMN research mainly focuses on tissue genetics, tumor marker detection, and cyst fluid analysis, with encouraging results (Thornton et al, 2013;Aronsson et al, 2018;Carr et al, 2018). However, no studies have comprehensively dissected the molecular changes throughout IPMN carcinogenesis (from the normal duct to IPMA, IPMC and to invasive).…”

Early screening and diagnosis strategies of pancreatic cancer: a comprehensive review

“…More recently, glycoproteomics has emerged as a subfield of proteomics, and tumor-specific variations in protein glycosylation may also contribute to the early diagnosis of pancreatic cancer. Aronsson et al [76] identified ten glycoprotein biomarker candidates through mapping the glycosylation profile of 1000 proteins, and subsequently verified these in serum samples from patients with pancreatic cancer. The panel including CA19-9, IL.17E, B7.1, and DR6 showed an AUC of 0.988 at 100% sensitivity and 90% specificity for discriminating stage I pancreatic cancer from healthy controls, which was more effective than CA19-9.…”

Pancreatic Tumorigenesis: Precursors, Genetic Risk Factors and Screening

“…The tumor-specific alterations may involve protein glycosylation which may potentially mapped and therefore assessed in the early detection of PC. Aronsson et al [ 212 ] created a panel that included IL.17E, B7.1, and DR6, in addition to CA19-9, to identify PC. These biomarkers showed 100% and 90% sensitivity and specificity, respectively, in a patient with stage 1 PC.…”