Does Alpha-2-macroglobulin (α2M) predicts breast cancer development or progression? (ISSN 2753-8176 (online))

1. Ana Pedro

1.Gwyntwr1386 Health & Social Care, Harold Tomlin Day Centre, 24 Grosvenor Street, Chester, CH1 2DD, info@gwyntwr1386.com

Introduction, Results and Discussion

Alpha-2-macroglobulin (α2M) is a large protein found in the blood which is mainly produced by the liver. α2M is the largest major non-immunoglobulin protein in human plasma (1).

It functions as a broad-spectrum protease inhibitor which are involved in various biological processes such as inflammation, cell growth, and blood clotting (2). α2M can also bind to and regulate cytokines and growth factors, thus influencing the immune system response (3). α2M also may play a role in various cancers and has been implicated in the development of some cancers and also as a tumor suppressor in other cancer types (4).

α2M may act as an anticancer agent by inhibiting proteases, which are enzymes that can promote tumor growth and metastasis. It can also bind to and neutralize growth factors and cytokines, potentially slowing down cancer cell proliferation (5). However, α2M may also promote tumor growth and metastasis by interacting with other molecules like LRP1 (Low Density Lipoprotein Receptor-related Protein 1) (6). Studies suggest that α2M levels might be altered in various cancer types, potentially making it a useful biomarker for diagnosis and prognosis (7).

Here we investigate if plasma-derived could predict breast cancer development or progression. We analyzed plasma samples derived from breast cancer patients (table 1) and and control individuals by proteomics analysis and FunRich analysis (figs. 1 and 2). By FunRich Venn diagram analysis, we found out that control samples, female 1, female 2 and male 2 had a good percentage of common proteins with cancer patient plasma sample CF110 (fig 1, green circles). We further analyze these samples by FunRich Venn diagram analysis and found a group of 150 proteins was common between control samples, female 1, female 2 and male 2 and cancer patient CF110 sample (fig.2, green arrow).

By analyzing the previously selected 150 proteins, we found out α2M had an huge score in female 2, 1, male 1 and CF110 samples (table 2). By comparing controls samples, female 1, female 2 and male 2 with early cancer patient CF5 and CF27 samples, we can see that these control samples have much bigger α2M scores than the mentioned cancer samples, while male 1 control sample seems to have a smaller score than all the control and cancer samples except for samples CF5 and CF1. This suggests that high levels of α2M in controls might be related with cancer development. Also, sample CF110 has a bigger α2M score than samples CF37 and CF5, suggesting than cancer progression might be related with higher α2M levels. Finally, samples CF1, CF25, CF27 and CF33 show progressive bigger α2M scores suggesting once again bigger α2M might be related with cancer progression. Further studies with much bigger number of samples are needed to ascertain if these preliminary results are correct.

Materials and methods

As per Pedro and Tucker (2018) (8). You can consult all proteomics data in this article.

References

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2. Armstrong PB, Quigley JP (1999). "Alpha2-macroglobulin: an evolutionarily conserved arm of the innate immune system". Developmental and Comparative Immunology. 23 (4–5): 375–390.

3. Van Leuven F, Cassiman JJ, Van den Berghe H (December 1986). "Human pregnancy zone protein and alpha 2-macroglobulin. High-affinity binding of complexes to the same receptor on fibroblasts and characterization by monoclonal antibodies". Journal of Biological Chemistry. 261 (35): 16622–16625.

4. Kontomanolis et al (2020). Role of Oncogenes and Tumor-suppressor Genes in Carcinogenesis: A Review.Anticancer Research November 2020, 40 (11) 6009-6015; DOI: https://doi.org/10.21873/anticanres.14622

5. Yang et al. (2020). The role of tumor-associated macrophages (TAMs) in tumor progression and relevant advance in targeted therapy.Acta Pharm Sin B. 2020 Apr 19;10(11):2156–2170.

6. Xing et al, 2016. Roles of low-density lipoprotein receptor-related protein 1 in tumors.Chin J Cancer. 2016 Jan 6;35:6.

7. Lee et al, 2022. Alpha-2-macroglobulin as a novel diagnostic biomarker for human bladder cancer in urinary extracellular vesicles. Front. Oncol., 13 September 2022 Sec. Genitourinary Oncology Volume 12 - 2022 |

8. Tucker and Pedro (2018).Blood-derived non-extracellular vesicle proteins as potential biomarkers for the diagnosis of early ER+ breast cancer and detection of lymph node involvement. F1000Research 2018, 7:283 (https://doi.org/10.12688/f1000research.14129.3)