Abstract
Background
Skin cutaneous melanoma (SKCM) is a highly aggressive disease with a poor prognosis for advanced tumors. Anoikis is a caspase-dependent cell death process triggered by extracellular matrix (ECM) detachment, rectifies detachment-induced metabolic defects that compromise cell survival, recent study revealed the crucial role of anoikis for cancer cells to survive during metastasis. However, limited research focused on the role of anoikis in SKCM.
Methods
Our study utilized the 27 anoikis-related genes (ARGs) to divide SKCM patients into two clusters, and obtain differentially expressed genes (DEGs) for each cluster. These DEGs were used in stepwise Cox regression analysis to develop a prediction model for SKCM patients consisting of nine ARGs, called the anoikis-related signature (ARS). Subsequently, we used the risk scores calculated from the ARS to divide SKCM patients into two groups and explored differences in immune microenvironment, immune checkpoint reactivity, and drug sensitivity between the groups.
Results
Nine ARGs were identified to stratify SKCM patients into two risk groups, patients in the high-risk group had a poor prognosis and suppressed immune cell infiltration. Moreover, higher expression of immune checkpoint molecules and a greater sensitivity to immunotherapy and chemotherapy drugs were observed in the low-risk group. Finally, all of the ARS hub genes were found to be upregulated in SKCM tissues and cell lines.
Conclusion
A novel ARGs signature was identified for predicting the prognosis of SKCM. Based on the immune landscape associated with ARS discovered in our study, targeting ARS hub genes may be a promising treatment for SKCM.
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Availability of data and materials
No sequencing was performed in this study, the datasets generated during and/or analyzed during the current study are available in the TCGA database (https://www.cancer.gov/ccg/research/genome-sequencing/tcga) and GEO database (https://www.ncbi.nlm.nih.gov/geo/).
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Funding
The Wisdom Accumulation and Talent Cultivation Project of the Third Xiangya Hospital of Central South University (YX202201); Outstanding Youth Project of Hunan Provincial Natural Science Foundation (2022JJ20093); Youth Project of National Natural Science Foundation of China (82202391). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by ZY and DW. The first and revised draft of the manuscript was written by XL and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Central South University (Date2023.03.06/No快23128). And informed consent has been obtained from all subjects and/or their legal guardians.
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Yue, Z., Wang, D. & Li, X. A promising anoikis-related prognostic signature predicts prognosis of skin cutaneous melanoma. J Cancer Res Clin Oncol 149, 17757–17770 (2023). https://doi.org/10.1007/s00432-023-05468-6
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DOI: https://doi.org/10.1007/s00432-023-05468-6