Lymphoma is a common cancer that includes Hodgkin lymphoma (HL), among others. Excisional lymph node biopsy, immunohistochemistry, and in situ hybridization are used to diagnose and classify lymphoma. However, invasive biopsies have significant limitations and risks, and they do not take into account differences between and within tumors because they only take a sample from one spot inside a single tumor lesion.
This study, published in the Journal of Clinical Oncology for the 2022 ASCO Annual Meeting, was performed to evaluate if the standard protein marker CA125 could be used for lymphoma screening when combined with the genomic features copy number aberrations (CNA) and fragment size (FS) of cell-free DNA (cfDNA).
A total of 135 untreated stage I–IV lymphoma patients and 399 healthy people were included in the study. Following recruitment, each participant had 8 mL of peripheral blood drawn. Cell-free DNA (cfDNA) was collected and subjected to shallow whole-genome sequencing (sWGS), while plasma was employed in part to measure the expression of seven tumor serum protein markers.
The researchers created a new blood-based assay that combined the latest next-generation technology of sWGS of cfDNA and protein marker CA125 with artificial intelligence (AI). The cancer risk score (CRS) of each sample was determined using this multidimensional assay and was used for early diagnosis of lymphoma.
After each protein marker was compared between lymphoma and healthy groups, only CA125 could be utilized to screen for lymphoma with a sensitivity of 25.9% and a specificity of 98.0%.
In terms of cfDNA genomic features, CNA and FS were significantly different between lymphoma and healthy groups. Compared to CA125, both FS and CNA showed improved sensitivity, 36.3% and 67.4%, respectively. When the three signatures were incorporated into the CRS model, the best results were obtained: 95 lymphoma cases were diagnosed with a sensitivity of 70.4% and a specificity of 98%. The sensitivity was 40% in stage I/II lymphoma cases and 85.7% in stage III/IV lymphoma cases.
For each lymphoma subtype, lymphoma from B-cells demonstrated better sensitivity than lymphoma from NK/T cells (71.0 % vs. 64.3 %), especially in HL (91.7 %).
In closing, the protein marker CA125 could be used for lymphoma screening in general and HL screening in particular when combined with the genomic features CNA and FS of cfDNA [1].
Source:
[1] Chang, Y., Wang, X., Li, Z., Geng, S., Zhu, D., Li, S., Wu, W., Chang, F., Chang, Y., Zhang, M., & Mao, M. (2022, May). Non-invasive detection of lymphoma with circulating tumor DNA features and plasma protein marker. 2022 ASCO Annual Meeting, Chicago, IL. https://meetings.asco.org/abstracts-presentations/209311
