NEW YORK – New research suggests protein markers found in blood serum can help identify individuals with pancreatic cancer before other suspicious symptoms arise.
The findings appeared in Cell Genomics on Wednesday.
"By utilizing prospective cohorts, we have identified circulating protein biomarkers that can predict [pancreatic cancer] incidence years before diagnosis," co-senior and co-corresponding authors Chaolong Wang and Jiang Chang, environmental health, epidemiology, and biostatistics researchers with Huazhong University of Science and Technology, and their colleagues wrote.
In addition, they noted that the study's findings "have important implications for [pancreatic cancer] screening and highlight the potential of these proteins as early diagnostic biomarkers and therapeutic targets."
Starting with a group of nearly 38,300 elderly individuals from China who were prospectively followed for almost six years, on average, researchers from the Huazhong University of Science and Technology and Fudan University's Greater Bay Area Institute of Precision Medicine identified 57 individuals who developed pancreatic cancer.
The team highlighted a handful of blood serum proteins — including REG1A, REG1B, TNF, and PLA2G1B — that appeared to coincide with future pancreatic cancer development in a subset of 40 matched case and control samples that were assessed across 1,463 blood serum proteins using the Olink Explore 1536 proximity extension assay panel.
When they brought in data for 52,705 UK Biobank Pharma Proteomics Project (UKB-PPP) participants, including 131 pancreatic cancer cases, the researchers were able to confirm associations for two of the four proteins, REG1A and REG1B, from a tandem cluster of REG1 family genes on chromosome 2.
The investigators saw further ties between REG1A and REG1B and pancreatic cancer when they performed a Mendelian randomization analysis that incorporated published protein quantitative trait locus data from UKB-PPP with dbGAP insights on pancreatic cancer risk variants found by genome-wide association in individuals of European ancestry.
"Our study, for the first time, showed that REG1A and REG1B proteins were elevated in the blood several years before the incidence of [pancreatic cancer], even after adjustment of the status of [type 2 diabetes], suggesting that REG1 proteins can signal the onset of [pancreatic cancer] before it progresses to an invasive stage," the authors reported.
That, in turn, points to the possibility of using such blood serum markers to identify individuals who would benefit from computed tomography (CT)-based screening and earlier-than-usual diagnostic biopsies, they suggested, arguing that pancreatic cancer survival may be improved by these and other screening and intervention strategies.
Because REG1 proteins are synthesized in the islet beta cells and are involved in islet cell regeneration and diabetogenesis, the researchers hypothesized that pancreatic lesions causing islet cell damage would stimulate the cytothesis cell repair process and proliferation of islet beta cells and thus activate the secretion of REG1 proteins.
Even so, they noted additional research will be needed to assess the mechanism behind the elevated REG1A and REG1B protein levels found in blood samples from individuals who go on to develop pancreatic cancer. Likewise, they explained, questions remain about the specificity of these markers, since higher-than-usual REG1 protein levels have been described in individuals with other cancer types, including lung and esophageal cancer.
"In general," the authors suggested, "the screening specificity can be improved by a combination of multiple biomarkers, including those from gastroscopy or CT scans."