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A pan-cancer analysis of STAT3 expression and genetic alterations in human tumors
1Department of Oncology, Guigang People's Hospital of Guangxi/The Eighth Affiliated Hospital of Guangxi Medical University, Guigang, Guangxi, China.
Abstract:
Combined cancer immunotherapy and targeted therapy have proven to be effective against various cancers and therefore have recently become the focus of cancer research. Signal transducer and activator of transcription 3 (STAT3) is a member of the STAT protein family of transcription factors. Several studies have shown that STAT3 can affect the prognosis of cancer patients by regulating immune microenvironment (IME). Therefore, STAT3 may have high research value for the development of combined immunotherapy/targeted therapy approaches for the treatment of cancer patients. We found differences in STAT3 expression between tumor and normal tissues. Kaplan-Meier survival and Cox regression analyses showed that high expression of STAT3 is associated with poor prognosis in low-grade glioma (LGG) patients. The results of the analysis of the area under the curve of the receiver operating characteristic curve further suggested that the expression of STAT3 is an effective way to evaluate the prognosis of patients with glioma. The results of the IME analysis revealed that the immune and matrix scores of LGGs were positively correlated with the expression of STAT3 (P < 0.05). The results of immune cell infiltration analysis showed that STAT3 was positively correlated with resting dendritic cells, eosinophils, neutrophils, M0 macrophages, M1 macrophages, CD4 memory resting T cells, and CD8 T cells in LGG patients, but negatively correlated with activated mast cells and M2 macrophages (P < 0.05). Our gene set enrichment analysis identified 384 enriched pathways. According to the enrichment scores, the top ten most significantly upregulated pathways were related to immune response. The top ten most significantly downregulated pathways were related to cell signal transduction and the regulation of cell survival, proliferation, and metabolism. Genetic alteration analysis showed that missense mutations in STAT3 account for the majority of mutations, and STAT3 mutations mostly occur in the Src homology domain. In conclusion overexpression of STAT3 can promote the development and growth of tumors by regulating IME, which is significantly related to the poor prognosis of cancer patients. Therefore, targeted inhibition of STAT3 expression may have high research value for the development of combined immunotherapy/targeted therapy approaches for the treatment of cancer patients.
Insights
Signal transducer and activator of transcription 3 (STAT3) overexpression promotes tumor growth by altering the immune microenvironment, correlating with poor prognosis in low-grade glioma. Targeted STAT3 inhibition shows promise for combined cancer therapies.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Combined cancer immunotherapy and targeted therapy are emerging as effective treatments.
- Signal transducer and activator of transcription 3 (STAT3) influences cancer prognosis by regulating the immune microenvironment (IME).
Purpose of the Study:
- To investigate the role of STAT3 in low-grade glioma (LGG) and its association with prognosis and the IME.
- To explore STAT3 as a potential target for combined immunotherapy and targeted therapy.
Main Methods:
- Kaplan-Meier survival and Cox regression analyses were used to assess prognosis.
- Immune microenvironment (IME) and immune cell infiltration analyses were performed.
- Gene set enrichment analysis and genetic alteration analysis were conducted.
Main Results:
- High STAT3 expression was linked to poor prognosis in LGG patients and served as an effective prognostic indicator.
- STAT3 expression positively correlated with immune and matrix scores and infiltration of various immune cells, while negatively correlating with others.
- Enrichment analysis revealed STAT3's significant role in immune response, cell signaling, and metabolism pathways. STAT3 mutations predominantly occurred in the Src homology domain.
Conclusions:
- STAT3 overexpression promotes tumor development by regulating the IME, leading to poor prognosis in cancer patients.
- Targeted inhibition of STAT3 presents a promising strategy for developing combined immunotherapy and targeted therapy approaches for cancer treatment.
