Key biomarkers for early diagnosis of pancreatic cancer identified

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 panel of serum proteins to identify protein biomarkers for

pancreatic cancer at an early stage. They used a Mendelian randomization approach to evaluate the potential causal effects of these proteins in the development of pancreatic cancer.

Pancreatic cancer is the third leading cancer cause of death, and when diagnosed late, the five-year survival rate is only 10%. However, detecting cancer in its early stages 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 its early detection.

Traditional cancer biomarkers such as carcinoembryonic antigen and carbohydrate antigens 19-9, 125 and 242 have shown varying specificities for pancreatic cancer. Inflammatory proteins such as tumor necrosis factor (TNF), C-reactive protein (CRP), and interleukin-6 (IL-6) also did not show significant associations with pancreatic cancer.

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, researchers analyzed a prospective cohort to identify and evaluate serum protein biomarkers that can be used to detect pancreatic cancer. Participants included 44 pairs of older adults with pancreatic cancer and their healthy controls, matched by age, sex, date of blood draw, and hospital. The average age of the participants was 68.48 years and 45% were male. The observational data covered 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 normalized protein expression (NPX) values. Various baseline characteristics such as smoking status, alcohol consumption level, educational 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 was used to examine the gene expression profile of each protein in 54 tissues. Sensitivity analyzes were also performed after stratifying data by sex and adjusting for type 2 diabetes.

Data from the U.K. Biobank Pharma Proteomics Project were used to analyze the replication of key protein biomarkers. Additionally, a Mendelian randomization approach was used to evaluate the potential causal effects of the identified proteins in the development of pancreatic cancer.

The study identified four proteins associated with pancreatic cancer: phospholipase A2 group IB (PLA2G1B), tumor necrosis factor (TNF) and regenerating protein family (REG) family members 1A and 1B. Of these, REG1A and REG1B proteins were confirmed using data from UK Biobank. In addition, Mendelian randomization analyzes using genome-wide association data and quantitative trait loci 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 causative variant. Moreover, 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.

Researchers hypothesized that tumors or lesions in the pancreas stimulate β-cell proliferation, which leads to abnormal secretion of REG1 proteins. In addition, the C-type lectin domain present on REG1 proteins can bind to carbohydrates on the surface of tumor cells and promote malignant growth.

In this study, researchers examined circulating proteins to identify potential biomarkers for pancreatic cancer. Two proteins, REG1A and REG1B, have been identified that have causative effects in the development of pancreatic cancer and are also elevated in lung and esophageal cancer. These results highlight the potential of REG1A and REG1B proteins for use in early detection and large-scale screening of pancreatic cancer.