Related Experiment Video
Updated: May 24, 2025
Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Unveiling ac4C modification pattern: a prospective target for improving the response to immunotherapeutic strategies
Jianlan Liu1, Pengpeng Zhang2, Chaoqin Wu1
1Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Abstract:
Emerging evidence has confirmed the inextricable connection between N4-acetylcytidine (ac4C) mRNA modification and the clinical characteristics of malignancies. Nonetheless, it is uncertain whether and how ac4C mRNA modification patterns affect clinical outcomes in melanoma patients. This research integrated single-cell sequencing data and transcriptomics to pinpoint ac4C-related genes (acRG) linked to melanoma progression and evaluate their clinical implications. Cells with elevated acRG score were predominantly located within the melanocytes cluster. Intercellular communications between melanocytes and other cell subtypes were markedly strengthened in the acRG-high group. We developed and confirmed an excellent acRG-related signature (acRGS) utilizing a comprehensive set of 101 algorithm combinations derived from 10 machine learning algorithms. Hereby, the acRGS, including MYO10, ZNF667, MRAS, SCO2, MAPK10, PNMA6A, KPNA2, NT5DC2, BAIAP2L2 and NDST3, delineated ac4C-associated mRNA modification patterns in melanoma. The acRGS possesses distinctly superior performance to 120 previously reported signatures in melanoma and could predict the overall survival of melanoma patients across four external datasets. The substantial associations among immune checkpoint genes, immune cell infiltration, and tumor mutation burden with acRGS indicate that acRGS is helpful in identifying melanoma patients who are sensitive to immunotherapy. Besides, we confirmed that MYO10 was mainly overexpressed in melanoma tissues, and elevated MYO10 was positively correlated with malignant phenotypes and unfavorable prognosis in melanoma patients. Silencing MYO10 expression inhibited melanoma cell proliferation, migration and invasion in vitro as well as tumor growth in vivo. Taken together, the acRGS could function as a reliable and prospective tool to improve the clinical prognosis for melanoma individuals.
Insights
This study identifies N4-acetylcytidine (ac4C) mRNA modification patterns and related genes (acRG) that impact melanoma patient outcomes. The developed ac4C-related signature (acRGS) predicts survival and immunotherapy response in melanoma.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- N4-acetylcytidine (ac4C) mRNA modification is linked to cancer, but its role in melanoma clinical outcomes remains unclear.
- Understanding ac4C patterns can reveal new biomarkers for melanoma progression and treatment response.
Purpose of the Study:
- To investigate the association between ac4C mRNA modification patterns and clinical characteristics in melanoma.
- To identify ac4C-related genes (acRG) and develop a predictive signature (acRGS) for melanoma patient prognosis and immunotherapy sensitivity.
Main Methods:
- Integrated single-cell sequencing and transcriptomics data to identify acRG in melanoma.
- Developed and validated an acRG-related signature (acRGS) using machine learning algorithms.
- Analyzed associations between acRGS, immune checkpoints, immune cell infiltration, tumor mutation burden, and MYO10 expression.
Main Results:
- Elevated acRG scores were associated with melanocyte clusters and enhanced intercellular communication.
- The 10-gene acRGS accurately predicted overall survival in melanoma patients across multiple datasets.
- acRGS showed strong correlations with immune biomarkers, suggesting potential for predicting immunotherapy response.
- MYO10 overexpression was linked to aggressive melanoma phenotypes and poor prognosis; its silencing inhibited tumor growth.
Conclusions:
- The acRG signature (acRGS) serves as a robust biomarker for predicting melanoma patient prognosis and response to immunotherapy.
- MYO10 is a potential therapeutic target for melanoma, as its inhibition affects tumor progression.
- ac4C modification patterns offer a novel avenue for improving clinical management of melanoma.
More Related Videos
09:53Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens
Published on: February 6, 2017
12:55Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care
Published on: February 16, 2015
Related Concept Videos
01:27Tumor Immunotherapy
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
01:30Cancer Vaccines
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...
01:27Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...