Tumor immune microenvironment in endometrial cancer of different molecular subtypes: evidence from a retrospective observational study

Dai, Yifei; Zhao, Lei; Hua, Dingchao; Cui, Lina; Zhang, Xiaobo; Kang, Nan; Liu, Qu; Li, Liwei; Li, He; Shen, Danhua; Wang, Zhiqi; Wang, Jianliu

doi:10.3389/fimmu.2022.1035616

Cited by 10 publications

(16 citation statements)

References 53 publications

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“…As we known, copy number high EC patients with the worst prognosis [48]. Previous studies have indicated that MSI type was observed relatively high percentages of CD8+T cells [49] and could benefit a lot from ICI [50,51], which was consistent with the results we have found. These findings confirm once again that EC patients in the low-risk group could be the potential ICI treatment candidates.…”

Section: Discussionsupporting

confidence: 91%

Identification of an immune-related metabolic gene signature to predict possible prognosis in endometrial cancer and reveals immune landscape feature

2023

European Journal of Gynaecological Oncology

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The immunotherapy of endometrial cancer (EC) has gradually attracted attention and metabolic reprogramming is associate with tumor immune infiltration. Our goal was to use proteome analysis to examine the role of immune-related metabolic genes (IRMGs) in EC. Data-independent acquisition mass spectrometry (DIA-MS) was performed on 20 EC patients, consisting of 10 high-grade and 10 low-grade cancer tissues. IRMGs were screened using Spearman correlation, and an immune-related metabolic prognosis signature (IRMPS) was constructed based on the Cancer Genome Atlas-Uterine Corpus Endometrioid Carcinoma (TCGA-UCEC) cohort using the least absolute shrinkage and selection operator (LASSO) regression analysis. We also investigated differences between different risk groups in terms of prognostic value, clinical potency, immune characteristics and therapy response. In total, 285 differentially expressed genes (DEGs) were acquired via DIA-MS. Subsequently, metabolic-DEGs and immune-DEGs were analyzed by Spearman correlation to identify 41 IRMGs. Finally, seven IRMGs, including NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 2 (NDUFA2), AMPK-alpha2 (PRKAA2), syntaxin binding protein 1 (STXBP1), NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 9 (NDUFB9), ribosomal protein S27-like (RPS27L), lysolecithin acyltransferase 2 (LPCAT2) and uridine monophosphate synthetase (UMPS) were identified to establish a prognosis signature. The risk score was determined as an independent prognostic indicator, and patients in the IRMPS-high group was strong linked with adverse prognosis for EC. Additionally, IRMPS was closely related with tumor immune infiltration. Notably, the IRMPS-low group had better immune checkpoint inhibitors (ICI) treatment response and more sensitive to chemotherapy drugs. In conclusion, IRMPS can serve as a precise prognostic tool to guide the personalized treatment of EC patients.

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Section: Discussionsupporting

confidence: 91%

Identification of an immune-related metabolic gene signature to predict possible prognosis in endometrial cancer and reveals immune landscape feature

2023

European Journal of Gynaecological Oncology

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“…Cai et al [ 33 ] clustered the samples according to the infiltration of immune cells in tumor tissues and obtained three subpopulations with high, intermediate, and low immune cell infiltration, namely, C I, C II, C III, among which C I and C II patients performed adjuvant treatment better. Another study from our group [ 10 ], combining molecular subtyping with the immune microenvironment, explored the immune microenvironment characteristics of different molecular subtyping, in which the tumor mutation burden (TMB) levels of POLE mutant and MSI-H cases were significantly higher than that of the other two subtypes ( P < 0.001). He combined POLE mutant and MSI-H subtypes into the TMB high (TMB-H) subtype.…”

Section: Discussionmentioning

confidence: 99%

“… Molecular subtyping: endometrial cancer tissue and blood samples from patients were collected, sequencing was performed using a high-throughput sequencer (Illumina products, USA), and sequencing data were analyzed using a high-throughput sequencing data analysis system (Amoy Diagnostics Co., Ltd.). Based on the sequencing results, in this study, we refer to the 2013 TCGA molecular classification method [ 2 ] to classify the patients into four subtypes: POLE ultramutated, MSI-H, CNL, and CNH, and the specific subtyping was performed using Trans-PORTEC [ 9 ], as follows: (1) the mutation status of the POLE gene was detected if the pathogenic mutation of the POLE gene was judged to be POLE ultramutated; (2) a microsatellite instability (MSI) value ≥ 0.4 in a sample wild-type for the POLE gene was judged as MSI-H type; (3) TP53 mutation status was determined in microsatellite stable patients and CNH and cases without mutation were judged as CNL [ 10 ]. Immunohistochemistry: ER, PR, p53, and Ki-67 expression were detected by immunohistochemistry with an envision kit purchased from Zymed (USA).…”

Section: Methodsmentioning

confidence: 99%

Re-stratification of patients with copy-number low endometrial cancer by clinicopathological characteristics

Liwei,

He,

Yibo

et al. 2023

World J Surg Onc

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Objective To stratify patients with copy-number low (CNL) endometrial cancer (EC) by clinicopathological characteristics. Methods EC patients who underwent surgery between June 2018 and June 2022 at Peking University People’s Hospital were included and further classified according to TCGA molecular subtyping: POLE ultramutated, microsatellite instability high (MSI-H), CNL, and copy-number high (CNH). Clinicopathological characteristics and prognosis of CNL patients were retrospectively reviewed. The Cox proportional hazards regression model was applied to perform univariate and multivariate analysis, and independent risk factors were identified. Differentially expressed genes (DEGs) according to overall survival (OS) were screened based on the transcriptome of CNL cases from the TCGA program. Finally, a nomogram was established, with an accuracy analysis performed. Results (1) A total of 279 EC patients were included, of whom 168 (60.2%) were in the CNL group. A total of 21 patients had recurrence and 6 patients deceased, and no significant difference in recurrence-free survival (RFS) was exhibited among the four molecular subtypes (P = 0.104), but that in overall survival (OS) was statistically significant (P = 0.036). (2) CNL patients were divided into recurrence and non-recurrence groups, and significant differences (P < 0.05) were found between the two groups in terms of pathological subtype, FIGO stage, ER, PR, glycated hemoglobin (HbA1c), and high-density lipoprotein cholesterol (HDL-C). All the above factors were included in univariate and multivariate Cox regression models, among which pathological subtype, PR, and HDL-C were statistically different (P < 0.05), resulting in three independent risk factors for the prognosis of patients in the CNL group. (3) By comparing the transcriptome of tumor tissues between living and deceased CNL patients from the TCGA database, 903 (4.4%) DEGs were screened, with four lipid metabolism pathways significantly enriched. Finally, a nomogram was established, and internal cross-validation was performed, showing good discrimination accuracy with an AUC of 0.831 and a C-index of 0.748 (95% CI 0.444–1.052). (4) According to the established nomogram and the median total score (85.89), patients were divided into the high score group (n = 85) and low score group (n = 83), and the 8 patients with recurrence were all in the high score group. Survival analysis was performed between the two groups, and the difference in RFS was statistically significant (P = 0.010). Conclusion In the CNL group of EC patients, pathological subtype, PR, and HDL-C were independent prognostic risk factors, the nomogram established based upon which had a good predictive ability for the recurrence risk of patients with CNL EC.

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“…Therefore, studying the ITME of different molecular subtypes is important. Recently studies on the ITME of different molecular types of EC have revealed that different molecular types may have different ITME (7,8). However impact of the ITME on EC remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Features of the immunosuppressive tumor microenvironment in endometrial cancer based on molecular subtype

Zhang,

Wang,

2023

Front. Oncol.

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Endometrial cancer (EC) is one of the three most prevalent gynecological tumors affecting women and is the most prevalent gynecological malignancy in the developed world. Its incidence is rapidly increasing worldwide, mostly affecting postmenopausal women, whereas recently its prevalence has increased in younger people. EC is an immune gene disease and many studies have shown that the tumor-immunosuppressive microenvironment plays an important role in cancer progression. In recent years, findings regarding the immunosuppressive tumor microenvironment (ITME) of EC have included immune evasion mechanisms and immunotherapy, which are mostly immune checkpoint inhibitors (ICI) for EC. Recently studies on the ITME of different molecular types of EC have found that different molecular types may have different ITME. With the research on the immune microenvironment of EC, a new immunophenotype classification based on the immune microenvironment has been carried out in recent years. However, the impact of the ITME on EC remains unclear, and the immunophenotype of EC remains limited to the research stage. Our review describes recent findings regarding the ITME features of different EC molecular types. The advent of immunotherapy has brought hope for improved efficacy and prognosis in patients with advanced or recurrent EC. The efficacy and safety of ICIs combination therapy remains the focus of future research.

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Tumor immune microenvironment in endometrial cancer of different molecular subtypes: evidence from a retrospective observational study

Cited by 10 publications

References 53 publications

Identification of an immune-related metabolic gene signature to predict possible prognosis in endometrial cancer and reveals immune landscape feature

Identification of an immune-related metabolic gene signature to predict possible prognosis in endometrial cancer and reveals immune landscape feature

Re-stratification of patients with copy-number low endometrial cancer by clinicopathological characteristics

Features of the immunosuppressive tumor microenvironment in endometrial cancer based on molecular subtype

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