Chen, Y.; Wu, W.; Jin, C.; Cui, J.; Diao, Y.; Wang, R.; Xu, R.; Yao, Z.; Li, X. Integrating Single-Cell RNA-Seq and Bulk RNA-Seq Data to Explore the Key Role of Fatty Acid Metabolism in Breast Cancer. Int. J. Mol. Sci.2023, 24, 13209.
Chen, Y.; Wu, W.; Jin, C.; Cui, J.; Diao, Y.; Wang, R.; Xu, R.; Yao, Z.; Li, X. Integrating Single-Cell RNA-Seq and Bulk RNA-Seq Data to Explore the Key Role of Fatty Acid Metabolism in Breast Cancer. Int. J. Mol. Sci. 2023, 24, 13209.
Chen, Y.; Wu, W.; Jin, C.; Cui, J.; Diao, Y.; Wang, R.; Xu, R.; Yao, Z.; Li, X. Integrating Single-Cell RNA-Seq and Bulk RNA-Seq Data to Explore the Key Role of Fatty Acid Metabolism in Breast Cancer. Int. J. Mol. Sci.2023, 24, 13209.
Chen, Y.; Wu, W.; Jin, C.; Cui, J.; Diao, Y.; Wang, R.; Xu, R.; Yao, Z.; Li, X. Integrating Single-Cell RNA-Seq and Bulk RNA-Seq Data to Explore the Key Role of Fatty Acid Metabolism in Breast Cancer. Int. J. Mol. Sci. 2023, 24, 13209.
Abstract
Abstract: (1) Background: Cancer immune escape is associated with the metabolic reprogramming of TME, and combining metabolic targets with immunotherapy has great potential to improve clinical outcomes. Among all metabolic processes, lipid metabolism, especially fatty acid (FA) metabolism, has a huge role in cancer cell survival, migration, and proliferation, but its mechanism and role in the tumor immune microenvironment remain to be investigated. (2) Methods: We comprehensively analyzed 309 fatty acid-related genes, screened 121 different genes, and used one-way COX regression to select 15 genes with prognostic impact. Systematically evaluated the correlation between FMGs modification patterns and Tumor Microenvironment Infiltration, prognosis, and Immunotherapy. The FMGs-Score was constructed to quantify the FMGs modification patterns using principal component analysis. (3) Results: Three clusters based on FMGs-related genes were demonstrated in breast cancer, with three patterns of distinct immune cell infiltration and biological behavior. An FMGsScore signature was constructed to reveal that patients with a low FMGsScore had higher immune checkpoint expression, higher immune checkpoint inhibitor (ICI) scores, increased immune microenvironment infiltration, better survival advantage, and were more sensitive to immunotherapy than those with a high FMGsScore. Finally, the expression and function of the signature key gene NDUFAB1 were examined by in vitro experiments. (4) Conclusions: This study significantly demonstrates the non-negligible role of FMGs in the immune microenvironment of breast cancer, and that FMGsScores can be used to guide the prediction of immunotherapy in breast cancer patients. In in vitro experiments, knockdown of the NDUFAB1 gene resulted in reduced proliferation and migration of MCF-7 cell lines.
Keywords
Fatty Acid Metabolism; Immunotherapy; Breast cancer; Tumor microenvironment; Single-cell sequencing
Subject
Biology and Life Sciences, Biology and Biotechnology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
