Integrated analysis reveals SMARCD1 is a potential biomarker and therapeutic target in skin cutaneous melanoma

• Published in: Journal of cancer research and clinical oncology 2023-10, Vol.149 (13), p.11619-11634
• Main Authors: Chen, Jiaoquan, Yu, Nanji, Ou, Shanshan, Wang, Xue, Li, Huaping, Zhu, Huilan
• Format: Article
• Language: English
• Subjects: Antitumor agents; Apoptosis; Biomarkers; Cancer; Cancer Research; Cell cycle; Cell migration; Cell proliferation; Chromatin remodeling; Chromosomal Proteins, Non-Histone; Drug development; Hematology; Humans; Immunosuppressive agents; Infiltration; Internal Medicine; Medical prognosis; Medicine; Medicine & Public Health; Melanoma; Melanoma - drug therapy; Melanoma - genetics; Melanoma, Cutaneous Malignant; Metastases; Microsatellite instability; Oncology; Risk factors; Skin; Skin Neoplasms - drug therapy; Skin Neoplasms - genetics; Therapeutic targets; Transcription factors; Tumor microenvironment; Tumor Microenvironment - genetics; Tumors
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-023-05064-8

Objective SMARCD1 is a part of the SWI/SNF chromatin remodeling complex family, which consists of transcription factors that are implicated in various types of cancer. Examining SMARCD1 expression in human cancers can provide valuable insights into the development and progression of skin cutaneous melanoma (SKCM). Methods Our study comprehensively examined the association between SMARCD1 expression and numerous factors, including prognosis, tumor microenvironment (TME), immune infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI) in SKCM. Then we utilized immunohistochemical staining to measure the SMARCD1 expression in both SKCM tissues and normal skin tissues. Furthermore, we conducted in vitro experimentation to evaluate the effects of SMARCD1 knockdown on SKCM cells. Results We found that aberrant expression of SMARCD1 across 16 cancers was strongly correlated with overall survival (OS) and progression-free survival (PFS). In addition, our research revealed that SMARCD1 expression is associated with multiple factors in different types of cancer, including immune infiltration, TME, immune-related genes, MSI, TMB, and sensitivity to anti-cancer drugs. SMARCD1 is likely involved in various SKCM signaling pathways and biological processes. Additionally, our research revealed that an SMARCD1-based risk factor model accurately predicted OS in SKCM patients. Furthermore, the downregulation of SMARCD1 expression demonstrated a significant inhibition of SKCM cell proliferation and migration, as well as an increase in apoptosis and cell cycle arrest. Conclusion We conclude that SMARCD1 is a promising diagnostic, prognostic, and therapeutic biomarker for SKCM, and its expression has significant clinical implications for the development of novel treatment strategies.