Immune Characterization of Ovarian Cancer Reveals New Cell Subtypes With Different Prognoses, Immune Risks, and Molecular Mechanisms

Cong, Shanshan; Guo, Qiuyan; Cheng, Yan; He, Yanan; Zhao, Xibo; Kong, Chunli; Ning, Shangwei; Zhang, Guangmei

doi:10.3389/fcell.2020.614139

Cited by 10 publications

(11 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another notable bioinformatics tool based on support vector regression modeling, Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT), was developed to deconvolute cell types and dissect the cellular components at the transcription level ( Newman et al, 2015 ). This algorithm has been extensively used to investigate the immune infiltration fraction and the heterogeneity of the immune microenvironment in OC tissues ( An and Yang, 2020 ; Cong et al, 2020 ; Gao et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of CD8+ T Cell Related Biomarkers in Ovarian Cancer

Chen

Luo

et al. 2022

Front. Genet.

View full text Add to dashboard Cite

Background: Immunotherapy is a promising strategy for ovarian cancer (OC), and this study aims to identify biomarkers related to CD8+ T cell infiltration to further discover the potential therapeutic target.Methods: Three datasets with OC transcriptomic data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Two immunotherapy treated cohorts were obtained from the Single Cell Portal and Mariathasan’s study. The infiltration fraction of immune cells was quantified using three different algorithms, Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT), and microenvironment cell populations counter (MCPcounter), and single-sample GSEA (ssGSEA). Weighted gene co-expression network analysis (WGCNA) was applied to identify the co-expression modules and related genes. The nonnegative matrix factorization (NMF) method was proposed for sample classification. The mutation analysis was conducted using the “maftools” R package. Key molecular markers with implications for prognosis were screened by univariate COX regression analysis and K-M survival analysis, which were further determined by the receiver operating characteristic (ROC) curve.Results: A total of 313 candidate CD8+ T cell-related genes were identified by taking the intersection from the TCGA-OV and GSE140082 cohorts. The NMF clustering analysis suggested that patients in the TCGA-OV cohort were divided into two clusters and the Cluster 1 group showed a worse prognosis. In contrast, Cluster 2 had higher amounts of immune cell infiltration, elevated ssGSEA scores in immunotherapy, and a higher mutation burden. CSMD3, MACF1, PDE4DIP, and OBSCN were more frequently mutated in Cluster 1, while SYNE2 was more frequently mutated in Cluster 2. CD38 and CXCL13 were identified by univariate COX regression analysis and K-M survival analysis in the TCGA-OV cohort, which were further externally validated in GSE140082 and GSE32062. Of note, patients with lower CXCL13 expression showed a worse prognosis and the CR/PR group had a higher expression of CXCL13 in two immunotherapy treated cohorts.Conclusion: OC patients with different CD8+ T cell infiltration had distinct clinical prognoses. CXCL13 might be a potential therapeutic target for the treatment of OC.

show abstract

Section: Introductionmentioning

confidence: 99%

Identification of CD8+ T Cell Related Biomarkers in Ovarian Cancer

Chen

Luo

et al. 2022

Front. Genet.

View full text Add to dashboard Cite

show abstract

“…Previous studies managed to portray the immune landscape of the OC microenvironment (11,12), yet the relationship between TME immunological features and the prognosis of patients receiving platinum-based adjuvant chemotherapy has been left undiscovered. In this study, we gather a large number of samples for identifying five robust ISs, therefore confirming that these subtypes with unique microenvironmental characteristics are indeed related to the prognosis of platinum-based therapy.…”

Section: Introductionmentioning

confidence: 99%

The Immune Subtype Contributes to Distinct Overall Survival for Ovarian Cancer Patients With Platinum-Based Adjuvant Therapy

Wang²,

Chen³

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

ObjectiveNowadays, platinum-based therapy has been widely used as the first-line therapy of ovarian cancer. However, the effect of the tumor microenvironment on platinum-based therapy remains unclear. In this study, we aim to investigate the relationship between immune microenvironment subtypes and the prognosis of platinum-based therapy in ovarian cancer.MethodsWe integrated 565 ovarian cancer samples from two datasets and obtained the immune subtypes (ISs) by consistent clustering of 1190 immune-related gene expressions. The proportional hazards regression model was used to assess the relationship between ISs and the prognosis of platinum-based adjuvant therapy including progression-free survival (PFS) and overall survival (OS). The prognostic contribution of ISs was validated in three additional cohorts. Non-parametric tests were used to assess genomic characteristics, the proportion of immune cells, and immune-related signature differences among ISs.ResultsWe identified and validated five ISs associated with different clinical outcomes of the platinum-based adjuvant therapy in ovarian cancer patients. These differences were only found in OS rather than PFS. An immune subtype had the worst OS. Those patients mainly derived from the mesenchymal subtype had the lowest tumor purity with a high leukocyte fraction as well as stromal fraction and had the highest TGF-β response signaling. By contrast, an immune subtype characterized by immunoreactive status with the highest CD8+T cell infiltration and elevated IFN-γ response signaling had the best prognosis. Other subtypes with more diverse immunologic features such as lowest macrophage regulation signaling showed intermediate prognoses. Notably, the contribution of ISs to OS was independent of the clinical response to platinum-based drugs.ConclusionOur analysis revealed the association between different immune characteristics and platinum-based adjuvant therapy, indicating the combination of ISs and chemotherapy could optimize the treatment strategy of OC patients.

show abstract

“…Despite through the effort that the first-line treatment focuses on surgery, chemotherapy follow-up and systemic treatment such as molecularly targeted drugs and antibodies, 5-year survival rate for EOC patients still remains beneath 20%. Resistance is frequently an important reason, as many factors (Azais et al, 2020;Cong et al, 2020;Xu et al, 2020;Zhang et al, 2021) that make EOC are usually untreatable. Therefore, studying the mechanism that affects the occurrence and development of ovarian cancer is essential for finding novel and reliable treatments for ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%