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Key biomarkers for early diagnosis of pancreatic cancer identified
Last reviewed: 02.07.2025
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In a recent study published in the journal Cell Genomics, a team of researchers from China conducted a case-control study to analyze a large set of serum proteins to identify protein biomarkers for early-stage pancreatic cancer. They used a Mendelian randomization approach to assess the potential causal effects of these proteins in the development of pancreatic cancer.
Pancreatic cancer is the third leading cause of cancer death, and when diagnosed late, the five-year survival rate is only 10%. However, detecting the cancer early can increase survival rates to 24%-37%. Given that pancreatic cancer progresses slowly, with an average of 11.7 years between the initial and invasive stages, there is ample time for early detection.
Traditional cancer biomarkers such as carcinoembryonic antigen and carbohydrate antigens 19-9, 125 and 242 showed different specificities for pancreatic cancer. Inflammatory proteins such as tumor necrosis factor (TNF), C-reactive protein (CRP) and interleukin-6 (IL-6) also showed no significant associations with pancreatic cancer incidence.
A blood test that includes all circulating proteins secreted by normal and damaged cells and tissues is a promising method for detecting cancer, since abnormalities in circulating proteins often indicate the development of tumors in the body.
In this study, the researchers analyzed a prospective cohort to identify and evaluate serum protein biomarkers that could be used to detect pancreatic cancer. Participants included 44 pairs of older adults with pancreatic cancer and their healthy controls, matched for age, sex, blood draw date, and hospital. The average age of participants was 68.48 years, and 45% were men. The follow-up data spanned approximately 5.7 years.
Circulating proteins were measured from fasting serum samples using a proximity extension assay. About 1500 proteins were measured and quantified using the normalized protein expression (NPX) value. Various baseline characteristics such as smoking status, alcohol consumption level, education level, glycemic indices, and body mass index were compared between pancreatic cancer cases and their healthy controls to identify categorical variables.
Protein expression values were standardized and odds ratios were calculated for each protein. Additionally, ribonucleic acid (RNA) data from the GTEx project were used to examine the gene expression profile of each protein in 54 tissues. Sensitivity analyses were also performed after stratifying data by sex and adjusting for type 2 diabetes.
Data from the UK Biobank Pharma Proteomics Project were used to analyse the replication of key protein biomarkers. Additionally, a Mendelian randomisation approach was used to assess potential causal effects of the identified proteins in pancreatic cancer development.
The study identified four proteins associated with pancreatic cancer: phospholipase A2 group IB (PLA2G1B), tumor necrosis factor (TNF), and regenerating protein (REG) family members 1A and 1B. Of these, REG1A and REG1B were validated using data from the UK Biobank. In addition, Mendelian randomization analysis using genome-wide association studies and quantitative trait loci data showed causal effects of REG1A and REG1B in pancreatic cancer development.
Colocalization analysis for REG1 proteins revealed moderate evidence that pancreatic cancer and REG1 proteins share a common causal variant. Furthermore, Mendelian randomization analysis found no evidence of other causal variants influencing the association between REG1 proteins and pancreatic cancer.
REG1 proteins have also been found at elevated levels in lung and esophageal cancers. These proteins are synthesized in the β-cells of the islets of Langerhans in the pancreas and are involved in the development of diabetes and islet cell regeneration.
The researchers hypothesized that tumors or lesions in the pancreas stimulate β-cell proliferation, leading to abnormal secretion of REG1 proteins. In addition, the C-type lectin domain present on REG1 proteins may bind to carbohydrates on the surface of tumor cells and promote malignant growth.
In this study, the researchers examined circulating proteins to identify potential biomarkers for pancreatic cancer. They identified two proteins, REG1A and REG1B, that have causal effects in the development of pancreatic cancer and are also elevated in lung and esophageal cancer. These findings highlight the potential of REG1A and REG1B proteins for use in early detection and large-scale screening of pancreatic cancer.