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Human blood cell transcriptomics unveils dynamic systemic immune modulation along colorectal cancer progression. | LitMetric

AI Article Synopsis

  • Colorectal cancer (CRC) is a major cause of cancer deaths, but early detection can reduce mortality; traditional methods like liquid biopsies have limitations in sensitivity during early stages of CRC.
  • This study analyzes blood samples to discover new RNA biomarkers related to CRC, revealing changes in immune cell activity that occur even before cancer develops.
  • The findings highlight a potential new approach for early CRC screening using a blood test that measures 226 biomarkers linked to immune response changes during CRC progression.

Article Abstract

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. CRC deaths can be reduced with prevention and early diagnosis. Circulating tumor DNA-based liquid biopsies, are emerging tools for cancer detection. However, the tumor-signal-dependent nature of this approach results in low sensitivity in precancerous and early CRC stages. Here we propose the host immune response to the onset of cancer as an alternative approach for early detection of CRC.

Methods: We perform whole transcriptome analysis of peripheral blood mononuclear cells (PBMCs) isolated from individuals with CRC, precancerous lesions or negative colonoscopy in two independent cohorts using next-generation sequencing.

Results: We discover and validate novel early CRC RNA biomarkers. Taking into account, and adjusting for, the sensitivity of PBMCs transcriptomes to processing times, we report distinct transcriptomic changes in the periphery related to specific CRC stages. Activation of innate immunity is already detectable in the peripheral blood of individuals with pre-malignant advanced adenomas. This immune response is followed by signs of transient B-cell activation and sustained inhibition of T-cell responses along CRC progression, whereby at late stages, protumoral myeloid cells, wound healing and coagulation processes prevail. Moreover, some biomarkers show similar dysregulation in tumors and are implicated in known pathways of CRC pathophysiology.

Conclusions: The strong systemic immune modulation triggered during CRC progression leads to previously unnoticed alterations detectable in PBMCs, paving the way for the development of an early CRC screening blood test, incorporating 226 validated biomarkers identified through immunotranscriptomics.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590809PMC
http://dx.doi.org/10.1136/jitc-2024-009888DOI Listing

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