The identification of a PTEN-associated gene signature for the prediction of prognosis and planning of therapeutic strategy in endometrial cancer.

Autor:	Zhang Y; Department of General Surgery, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, China.; Department of Obstetrics, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China., Li L; Department of Obstetrics and Gynaecology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, China., Ke XP; Department of Obstetrics and Gynaecology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, China., Liu P; Department of Obstetrics and Gynaecology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, China.
Jazyk:	angličtina
Zdroj:	Translational cancer research [Transl Cancer Res] 2023 Dec 31; Vol. 12 (12), pp. 3409-3424. Date of Electronic Publication: 2023 Dec 10.
DOI:	10.21037/tcr-23-1436
Abstrakt:	Background: Endometrial cancer (EC) is one of the most common malignancies among women. To improve the prognosis and treatment of EC, finding out a phosphatase and tensin homolog deleted on chromosome 10 (PTEN)-associated prognostic signature would be beneficial. Methods: EC clinical data, genetic mutation data, and transcriptome data were downloaded from The Cancer Genome Atlas (TCGA) database. To clarify the specific PTEN-associated signature, cox regression analyses were performed. The clinical value of the selected signature on the overall survival (OS) and the secretoglobin family 2A member 1 (SCGB2A1)-independent analysis, immune and functional analysis were investigated respectively. Results: Five hundred and fourteen EC samples were screened and PTEN mutation occupied 57%. Enrichment analysis indicated that mutant-type PTEN was enriched for pathways related to the upregulated human T-cell leukemia virus-1 (HTLV-1) infection and estrogen signaling pathway. SCGB2A1 was identified by cox regression analysis. Immune analysis exhibited significant immune infiltration with higher expression of T cells, B cells, and macrophage groups. Immune-checkpoint transcripts CD274 molecule (CD274), and cytotoxic T-lymphocyte associated protein 4 (CTLA4), hepatitis A virus cellular receptor 2 (HAVCR2), lymphocyte activation gene 3 (LAG3), programmed cell death 1 (PDCD1), PDCD1 ligand 2 (PDCD1LG2), T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), and sialic acid binding immunoglobulin like lectin 15 (SIGLEC15) were discovered statistically different. In addition, the low-SCGB2A1 group had worse OS than the high-SCGB2A1 group. SCGB2A1 showed significant area under the curve (AUC) values in a time-dependent receiver operating characteristic (ROC) analysis. Prevalence of microsatellite instability (MSI) was detected and SCGB2A1 showed a negative correlation with EC. Immune checkpoint blockade (ICB) response indicated a worse immune response in the low-SCGB2A1 group. The distribution of one-class linear regression (OCLR) scores reflected the negative correlation between messenger RNA expression-based stemness index (mRNAsi) and prognostic gene expression. Furthermore, several SCGB2A1-related signaling pathways in EC were identified. Conclusions: SCGB2A1 is a prognostic immunometabolic signature for patients with EC, which may help improve the prognosis and therapeutic effect. Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-1436/coif). The authors have no conflicts of interest to declare. (2023 Translational Cancer Research. All rights reserved.)
Databáze:	MEDLINE
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