An Observational Study on the Molecular Profiling of Primary Melanomas Reveals a Progression Dependence on Mitochondrial Activation

Cancers

Melinda Rezeli¹  Kun-Hsing Yu²  István Balázs Németh³  Nga Nguyen⁴  Yevgeniy R. Semenov⁴  Guihong Wan⁴  Elmar G. Lutz⁵  Sarolta Kárpáti⁵  Lajos V. Kemény⁵  Jeovanis Gil⁶  Yutaka Sugihara⁶  György Marko-Varga⁶  Yonghyo Kim⁶  Johan Malm⁷ 

[1] Clinical Protein Science & Imaging, Biomedical Centre, Department of Biomedical Engineering, Lund University, 222 42 Lund, Sweden;Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA;Department of Dermatology and Allergology, University of Szeged, 6720 Szeged, Hungary;Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02110, USA;Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, 1085 Budapest, Hungary;Division of Oncology, Department of Clinical Sciences, Lund University, 222 42 Lund, Sweden;Section for Clinical Chemistry, Department of Translational Medicine, Lund University, Skåne University Hospital Malmö, 205 02 Malmö, Sweden;

关键词: primary melanoma;    proteogenomics;    PTMs;    malignant melanoma;    mitochondria;    mitochondrial translation;   

DOI  :  10.3390/cancers13236066

来源: DOAJ

【 摘 要 】

Melanoma in advanced stages is one of the most aggressive tumors and the deadliest of skin cancers. To date, the histopathological staging focuses on tumor thickness, and clinical staging is a major estimate of the clinical behavior of primary melanoma. Here we report on an observational study with in-depth molecular profiling at the protein level including post-translational modifications (PTMs) on eleven primary tumors from melanoma patients. Global proteomics, phosphoproteomics, and acetylomics were performed on each sample. We observed an up-regulation of key mitochondrial functions, including the mitochondrial translation machinery and the down-regulation of structural proteins involved in cell adhesion, the cytoskeleton organization, and epidermis development, which dictates the progression of the disease. Additionally, the PTM level pathways related to RNA processing and transport, as well as chromatin organization, were dysregulated in relation to the progression of melanoma. Most of the pathways dysregulated in this cohort were enriched in genes differentially expressed at the transcript level when similar groups are compared or metastasis to primary melanomas. At the genome level, we found significant differences in the mutation profiles between metastatic and primary melanomas. Our findings also highlighted sex-related differences in the molecular profiles. Remarkably, primary melanomas in women showed higher levels of antigen processing and presentation, and activation of the immune system response. Our results provide novel insights, relevant for developing personalized precision treatments for melanoma patients.

【 授权许可】

Unknown