Analysis of Single-Cell RNA Sequencing Data Unveils Novel Immune Prognostic Biomarkers

The immune system plays a central role in recognizing and eliminating cancerous cells. The activity and functionality of immune cells within the tumor microenvironment can significantly impact the prognosis of cancer patients. Leveraging single-cell RNA sequencing technology, we conducted an in-depth investigation into single-cell-based gene signatures for predicting cancer patient survival. The study utilized single-cell RNA sequencing data from breast cancer patients, encompassing over 14,875 immune cells. Gene signatures from major innate immune cell types, including Natural Killer (NK) cells, Macrophages, and Neutrophils, as well as adaptive immune cells, including Cytotoxic T Lymphocytes (T cells) and B lymphocytes (B cells), were identified. To elucidate their relationship in breast cancer patients, we constructed Cox proportional hazard regression models for predicting patient survival, utilizing the concordance index as a measure of prediction model performance. The evaluation incorporated three independent breast cancer patient cohorts: TCGA (The Cancer Genome Atlas Program), METABRIC (Molecular Taxonomy of Breast Cancer International Consortium), and UK breast cancer data. Our results showed that the T cell-based signature model outperformed the NK cell-based and Neutrophil-based prediction models. Moreover, the
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cell-based signature model exhibited robust performance across independent patient datasets. These findings suggest that gene signatures derived from cells of the adaptive immune system have a better survival prediction value than those derived from the innate immune system, underscoring the potential clinical relevance of harnessing the adaptive immune response for refining prognostic assessments in breast cancer. These insights contribute to advancing our understanding of the complex interplay between immune cells and cancer prognosis, paving the way for more tailored and effective therapeutic interventions.