Putative breast cancer metastatic biomarkers in melanoma – short report (ISSN 2753-8176 (online))

1.Ana Pedro

1.Gwyntwr1386 CIC, U.K.

info@gwyntwr1386.com

We found out several putative plasma biomarkers for metastatic ER+ breast cancer prediction and diagnosis (1) and we decided to evaluate the presence of these biomarkers in lympathic fluid (LF) melanoma patient samples. We analyzed proteomic profiles of LF samples derived from control and melanoma patients detailed in table 1. We analyzed Mascot scores of specific proteins in each of these samples.

We found out that Serum Amyloid A-1 protein (P0DJI8, SAA1)), inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3, Q06033-2), ceruloplasmin (P00450) and complement C4 β chain (B0UZ83) maybe relevant in melanoma progression.

In table 2, are depicted our findings. SAA1 is not present in controls, but is significantly present in two of the no metastatic and two of the metastatic LF melanoma samples. Elevated circulating levels of SAA correlate with advanced tumor stages, high tumor load, and shorter overall or progression-free survival in melanoma patients. Moreover, melanoma and other cancer cells sometimes produce SAA. SAA interacts with the tumor microenvironment, induces cytokine release and stimulates immunosuppressive cells helping tumor cells evade T-cell immunity (2).

ITH3 also is not expressed in controls and is also expressed, significantly in two of the no metastatic and two of the metastatic LF melanoma samples. ITIH3 is linked to extracellular matrix (ECM) organization and tumor progression in melanoma (3) . Studies evaluating plasma and serum in melanoma have identified ITIH3 among protein signatures associated with melanoma progression or discrimination of progressive disease from stable or no evident disease (4).

Ceruloplasmin is significantly expressed in controls, no metastatic samples and shows a highly increased Mascot score in samples 2 (subcutaneous metastasis) and 5 (brain metastasis).Ceruloplasmin levels are often significantly elevated in patients with melanoma, serving as a potential marker for disease presence, tumor burden, and progression (5). Melanoma patients exhibit significantly higher mean serum ceruloplasmin levels (approx. 29.85 mg/dL) compared to healthy individuals (approx. 26.10 mg/dL) (6).

Finally, complement C4 β chain is significantly expressed in one of the controls and one of the non-metastatic samples, showing a hugely increased Mascot score in sample 5. Melanoma cells can actively synthesize and secrete complement components, including C4. Rather than destroying the cancer, local activation of these proteins can be hijacked by the tumor. Helpin to produce an immunosuppressive zone. This blocks local T-cell and natural killer (NK) cell activity, allowing melanoma cells to evade the immune system, enter vascular pathways, and metastasize (7,8).

Materials and Methods

Proteomic analysis was performed at the Rockefeller University, Proteomics Center as described in Hamidi et al., 2017 (1). Only proteins with Mascot scores of approximately 90 or >90 were considered (9). The proteomic analysis excel files and each correspondent sample details were generously and kindly shared and donated by Dr. David Lyden, Weill Cornell Medical College, New York, USA. Original data files can be found at https://zenodo.org/record/6635906#.YqX5JnbMLIU

References

1.Hamidi et al. (2017) Identification of potential blood-derived extracellular vesicles biomarkers to diagnose and predict distant metastases in ER+ breast cancer patients, bioRxiv preprint doi: https://doi.org/10.1101/202291

2. https://www.frontiersin.org/10.3389/conf.fimmu.2013.02.00912/event_abstract

3.https://isevjournals.onlinelibrary.wiley.com/doi/10.1002/jev2.12063

4. https://aacrjournals.org/clincancerres/article-abstract/30/1/159/732088/Proteomic-Profiling-of-Advanced-Melanoma-Patients?redirectedFrom=fulltext

5.https://pubmed.ncbi.nlm.nih.gov/11299817/

6.https://pubmed.ncbi.nlm.nih.gov/11299817/

7.https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.931273/full

8.https://pubmed.ncbi.nlm.nih.gov/39732132/