Proteins in the blood could warn people of cancer more than seven years before it is diagnosed

In a recent study published in Nature communication researchers from the United Kingdom (UK) investigated associations between 1,463 plasma proteins and 19 cancers, using observational and genetic approaches in participants of the UK Biobank. They found 618 protein-cancer associations and 317 cancer biomarkers, which included 107 cases detected over seven years before the diagnosis of cancer.

Background

Proteins are pivotal in most biological processes, including the development of cancer, with some serving as known cancer risk factors or biomarkers. While previous studies have identified individual cancer-related proteins, new multiplex proteomics techniques allow for simultaneous assessment of proteins at a high-scale, especially those that remain unexplored in the cancer risk context.

Prospective studies face challenges owing to confounding and biases, but genetic variations that affect protein levels offer complementary evidence. Genetic predictors, especially cis-pQTLs (short for cis protein quantitative trait loci), provide robust insights into protein-cancer associations. Integrating observational and genetic approaches enhances the identification of proteins potentially causally linked to cancer development and progression.

This combined methodology aids in understanding cancer biology, identifying therapeutic targets and discovering diagnostic biomarkers. Therefore, in the present study, researchers employed an integrated multi-omics strategy merging prospective cohort and exome-variant studies to reveal the proteins potentially implicated in the etiology of cancer.

About the study

The present study utilized data from the UK Biobank, a prospective cohort comprising 44,645 adults (post-exclusion) aged 39 to 73 years, followed up for a median of 12 years. Participants underwent assessments, including a questionnaire, anthropometric measurements, and blood sample collection. Plasma samples were analyzed using the Olink Proximity Extension Assay to quantify 1463 proteins. Cancer registration and death data were obtained through record linkage to national registries. Exome sequencing data were used to explore genetic associations with protein levels.

Results and discussion

Observational analyses showed 4921 incident cancer cases at a median age of 66.9 years. Individuals who developed cancer were found to be older, had higher rates of addictions, and family history of cancer compared to the total analysis sample. Women with cancer tended to have fewer children, earlier menarche, higher rates of postmenopausal status, hormone replacement therapy use, and no oral contraceptive pill use.

A total of 371 proteins showed significant associations with the risk of at least one cancer, resulting in 618 protein-cancer associations. A total of 304 of these associations were linked to proteins enriched in messenger ribonucleic acid (mRNA) expression in tissues or candidate cells of cancer origin. While many associations were observed for proteins related to hematological cancers with high mRNA expression in B-cells or T-cells, associations were also found for proteins with high mRNA expression in various other tissues such as the liver, kidneys, brain, stomach, lung, colorectum, esophagus, and endometrium.

Written by

Dr. Sushama R. Chaphalkar

Dr. Sushama R. Chaphalkar is a senior researcher and academician based in Pune, India. She holds a PhD in Microbiology and comes with vast experience in research and education in Biotechnology. In her illustrious career spanning three decades and a half, she held prominent leadership positions in academia and industry. As the Founder-Director of a renowned Biotechnology institute, she worked extensively on high-end research projects of industrial significance, fostering a stronger bond between industry and academia.