Development and Clinical Validation of Novel 8-Gene Prognostic Signature Associated With the Proportion of Regulatory T Cells by Weighted Gene Co-Expression Network Analysis in Uterine Corpus Endometrial Carcinoma

Abstract

BackgroundUterine corpus endometrial carcinoma (UCEC) is a gynecological malignant tumor with low survival rate and poor prognosis. The traditional clinicopathological staging is insufficient to estimate the prognosis of UCEC. It is necessary to select a more effective prognostic signature of UCEC to predict the prognosis and immunotherapy effect of UCEC.MethodsCIBERSORT and weighted correlation network analysis (WGCNA) algorithms were combined to screen modules related to regulatory T (Treg) cells. Subsequently, univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses were used to identify the genes in key modules. The difference in overall survival (OS) between high- and low-risk patients was analyzed by Kaplan–Meier analysis. The Tregs-related risk signature (TRRS) was screened by uni- and multivariate Cox analyses. Afterward, we analyzed the expression difference of TRRS and verified its ability to predict the prognosis of UCEC and the effect of immunotherapy.ResultsRed module has the highest correlation with Tregs among all clustered modules. Pathways enrichment indicated that the related processes of UCEC were primarily associated to the immune system. Eight genes (ZSWIM1, NPRL3, GOLGA7, ST6GALNAC4, CDC16, ITPK1, PCSK4, and CORO1B) were selected to construct TRRS. We found that this TRRS is a significantly independent prognostic factor of UCEC. Low-risk patients have higher overall survival than high-risk patients. The immune status of different groups was different, and tumor-related pathways were enriched in patients with higher risk score. Low-risk patients are more likely take higher tumor mutation burden (TMB). Meanwhile, they are more sensitive to chemotherapy than patients with high-risk score, which indicated a superior prognosis. Immune checkpoints such as PD-1, CTLA4, PD-L1, and PD-L2 all had a higher expression level in low-risk group. TRRS expression really has a relevance with the sensitivity of UCEC patients to chemotherapeutic drugs.ConclusionWe developed and validated a TRRS to estimate the prognosis and reflect the immune status of UCEC, which could accurately assess the prognosis of patients with UCEC and supply personalized treatments for them.

The Modifying Effect of Obesity on the Association of Matrix Metalloproteinase Gene Polymorphisms with Breast Cancer Risk

“…Importantly, the aforementioned adipose-specifically-expressed genes are impactful for cancer biology. For example, the important clinical and pathobiological significance of the ZSWIM1 gene ( SWIM-type zinc finger protein 1 ) was shown in uterine endometrial carcinoma: the expression of this gene in the tumor was lower than in normal tissue, but the high expression of this gene negatively correlated with overall survival; the ZSWIM1 methylation level was downregulated in cancer [ 61 ]. Pawar et al showed upregulation of the ZSWIM1 gene in ovarian cancer [ 62 ].…”

ZSWIM1 Promotes the Proliferation and Metastasis of Lung Adenocarcinoma Cells through the STK38/MEKK2/ERK1/2 Axis

“…In this study, we characterized the function of the uPE1 protein ZSWIM1 (C20orf162) in LUAD as an oncogene, which promoted the proliferation and metastasis phenotype (Figures and ). This has never been reported, as this protein was reported to function in T cells in the literature. , Other information about ZSWIM1 is shown in the Human Protein Atlas (). For example, ZSWIM1 exhibits low immune cell specificity.…”

“…Currently, there are 35 uPE1 proteins on chromosome 20 (, October 13, 2022). ZSWIM1 ( C20orf162 ), the zinc finger, swim-type containing 1 gene, an important paralog of ZSWIM3, binds to a zinc ion, locates on chromosome 20 and is an uPE1 with only two related papers in PubMed. , The ZSWIM1 gene encodes a protein of 485 amino acids and was shown to participate in the development or function of T helper cells. The other study reported that ZSWIM1 along with other seven proteins were used to construct the Tregs-related risk signature (TRRS) to estimate the prognosis and the immune status of uterine corpus endometrial carcinoma .…”

Analysis of the Prognostic Significance and Immune Infiltration of the Amino Acid Metabolism-Related Genes in Colon Adenocarcinoma

“…Growing evidence suggests that interactions between immune cells and metabolites might be significant in regulating immunity and tumor immunoevasion ( DePeaux and Delgoffe, 2021 ). Meanwhile, the screening of immune targets plays a key role in the immunotherapy of MSI-H colorectal cancer ( Liu J. et al, 2021 ; Liu et al, 2022 ). In our study, the group scoring lower had more immune cell infiltration, the cause of which can be explained as follows.…”