A nine-gene signature related to tumor microenvironment predicts overall survival with ovarian cancer

Ding, Qi; Dong, Shanshan; Wang, Ranran; Zhang, Keqiang; Wang, Hui; Zhou, Xiao Yan; Wang, Jing; Wong, Kee H.; Long, Ying; Zhu, Sipin; Wang, Weigang; Ren, Huayi; Zeng, Yong

doi:10.18632/aging.102914

Cited by 31 publications

(28 citation statements)

References 70 publications

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“…Very recently, upregulation of CXCL-11 was identified as a protective prognostic factor that significantly associated with overall survival of ovarian cancer. 49 Indeed, it has been shown in other study that CXCL-11 occurred in the serum of patients with cancer 2 weeks post-treatment of anti-PD1/PDL-1 and sustained up to 6 weeks post-treatment. 50 Interestingly, patients who developed immune-related adverse events had lower levels of CXCL-11 at baseline.…”

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confidence: 90%

Persistent anti-NY-ESO-1-specific T cells and expression of differential biomarkers in a patient with metastatic gastric cancer benefiting from combined radioimmunotherapy treatment: a case report

Merhi¹,

Raza²,

Inchakalody³

et al. 2020

J Immunother Cancer

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Combined radioimmunotherapy is currently being investigated to treat patients with cancer. Anti-programmed cell death-1 (PD-1) immunotherapy offers the prospect of long-term disease control in solid tumors. Radiotherapy has the ability to promote immunogenic cell death leading to the release of tumor antigens, increasing infiltration and activation of T cells. New York esophageal squamous cell carcinoma-1 (NY-ESO-1) is a cancer–testis antigen expressed in 20% of advanced gastric cancers and known to induce humoral and cellular immune responses in patients with cancer. We report on the dynamic immune response to the NY-ESO-1 antigen and important immune-related biomarkers in a patient with metastatic gastric cancer treated with radiotherapy combined with anti-PD-1 pembrolizumab antibody.Our patient was an 81-year-old man diagnosed with locally advanced unresectable mismatch repair-deficient gastric cancer having progressed to a metastatic state under a second line of systemic treatment consisting of an anti-PD-1 pembrolizumab antibody. The patient was subsequently treated with local radiotherapy administered concomitantly with anti-PD-1, with a complete response on follow-up radiologic assessment. Disease control was sustained with no further therapy for a period of 12 months before relapse. We have identified an NY-ESO-1-specific interferon-γ (IFN-γ) secretion from the patients’ T cells that was significantly increased at response (****p˂0.0001). A novel promiscuous immunogenic NY-ESO-1 peptide P39 (P153–167) restricted to the four patient’s HLA-DQ and HLA-DP alleles was identified. Interestingly, this peptide contained the known NY-ESO-1-derived HLA-A2-02:01(P157–165) immunogenic epitope. We have also identified a CD107+ cytotoxic T cell subset within a specific CD8+/HLA-A2-NY-ESO-1 T cell population that was low at disease progression, markedly increased at disease resolution and significantly decreased again at disease re-progression. Finally, we identified two groups of cytokines/chemokines. Group 1 contains five cytokines (IFN-γ, tumor necrosis factor-α, interleukin-2 (IL-2), IL-5 and IL-6) that were present at disease progression, significantly downregulated at disease resolution and dramatically upregulated again at disease re-progression. Group 2 contains four biomarkers (perforin, soluble FAS, macrophage inflammatory protein-3α and C-X-C motif chemokine 11/Interferon–inducible T Cell Alpha Chemoattractant that were present at disease progression, significantly upregulated at disease resolution and dramatically downregulated again at disease re-progression. Combined radioimmunotherapy can enhance specific T cell responses to the NY-ESO-1 antigen that correlates with beneficial clinical outcome of the patient.

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confidence: 90%

Persistent anti-NY-ESO-1-specific T cells and expression of differential biomarkers in a patient with metastatic gastric cancer benefiting from combined radioimmunotherapy treatment: a case report

Merhi¹,

Raza²,

Inchakalody³

et al. 2020

J Immunother Cancer

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“…In glioblastoma, the TME is strongly linked to gene expression and prognosis ( Cooper et al, 2012 ). In addition, cancer-associated fibroblasts (CAFs) enhance OC metastasis and induce upregulation of lipoma-preferred partner, which contributes to chemoresistance in OC ( Ding et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…Owing to advances in sequencing technologies, large amounts of bioinformatic data are available from public databases, including The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, enabling exploration of the association between TME and prognosis in tumors ( Zhang et al, 2019 ). The recently developed ESTIMATE algorithm can predict infiltration of non-tumor cells by evaluating specific gene expression in immune and stromal cells ( Ding et al, 2020 ). The ESTIMATE algorithm has been applied to various cancers, including prostate cancer, breast cancer, colon cancer, cutaneous melanoma, glioblastoma, and clear cell renal cell carcinoma ( Piperi et al, 2019 ; Bangbei et al, 2020 ; Yang H. et al, 2020 ; Yang S. et al, 2020 ; Zhang Z. et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Three Genes Predict Prognosis in Microenvironment of Ovarian Cancer

Guo

Wang

et al. 2020

Front. Genet.

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Ovarian cancer (OC) is the deadliest gynecological cancer in women. Immune cell infiltration has a critical role in regulating carcinogenesis and prognosis in OC. To identify prognostic genes relevant to the tumor microenvironment in OC, we investigated the association between OC and gene expression profiles. Results obtained with the ESTIMATE R tool showed that immune score and stromal score were correlated with lymphatic invasion, and high immune score predicted a favorable prognosis. A total of 342 common differentially expressed genes were identified according to the two scores; these genes were mainly involved in immune response, extracellular region, and serine-type endopeptidase activity. Three immune-related prognostic genes were selected by univariate and multivariate Cox regression analysis. We further established a prognostic model and validated the prognostic value of three hub genes in different databases; our results showed that this model could accurately predict survival and evaluate prognosis independent of clinical characteristics. Three hub genes have prognostic value in OC. TIMER analysis revealed that the three genes were correlated with different immune cells. Low levels of macrophage infiltration and high levels of CD4+ T cell infiltration were associated with favorable survival outcomes. Arm-level gain of GYPC was correlated with neutrophils and dendritic cells. These findings indicate that CXCR4, GYPC, and MMP12 modulate prognosis via effects on the infiltration of immune cells. Thus, these genes represent potential targets for immune therapy in OC.

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“…Previous studies have widely applied the ESTIMATE algorithm and clarified the meaningful relationship between microenvironment and multiple tumors, including glioblastoma [24], lung adenocarcinoma [25], gastric cancer [26], ovarian cancer [27],etc. The role of TME in AML has been explored and become a hotspot as well.…”

Section: Introductionmentioning

confidence: 99%

Identification of a Prognostic Gene Signature Associated with Microenvironment in Acute Myeloid Leukemia

Chen

Wang

et al. 2020

Preprint

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Background: Acute myeloid leukemia (AML) is a common hematologic malignancy with poor prognosis. Accumulating reports have indicated that the tumor microenvironment (TME) performs a critical role in the progress of the disease and the clinical outcomes of patients. To date, the role of TME in AML remains clouded due to the complex regulatory mechanisms in it. In this study, We identified key prognostic genes relate to TME in AML and developed a novel gene signature for individualized prognosis assessment. Methods: The expression profiles of AML samples with clinical information were obtained from the Cancer Genome Atlas (TCGA). The ESTIMATE algorithm was applied to calculate the TME relevant immune and stromal scores. The differentially expressed genes (DEGs) were selected based on the immune and stromal scores. Then, the survival analysis was applied to select prognostic DEGs, and these genes were annotated by functional enrichment analysis. A TME relevant gene signature with predictive capability was constructed by a series of regression analyses and performed well in another cohort from the Gene Expression Omnibus (GEO) database. Moreover, we also developed a nomogram with the integration of the gene signature and clinical indicators to establish an individually quantified risk-scoring system. Results: In the AML microenvironment, a total of 181 DEGs with prognostic value were clarified. Then a seven-gene ( IL1R2, MX1, S100A4, GNGT2, ZSCAN23, PLXNB1 and DPY19L2 ) signature with robust prediction was identified, and was validated by an independent cohort of AML samples from the GSE71014. Gene set enrichment analysis (GSEA) of genes in the gene signature revealed these genes mainly enriched in the immune and inflammatory related processes. The correlation between the signature-calculated risk scores and the clinical features indicated that patients with high risk scores were accompanied by adverse survival. Finally, a nomogram with clinical utility was constructed. Conclusion: Our study explored and identified a novel TME relevant seven-gene signature, which could serve as a prognostic indicator for AML. Meanwhile, we also establish a nomogram with clinical significance. These findings might provide new insights into the diagnosis, treatment and prognosis of AML.

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A nine-gene signature related to tumor microenvironment predicts overall survival with ovarian cancer

Cited by 31 publications

References 70 publications

Persistent anti-NY-ESO-1-specific T cells and expression of differential biomarkers in a patient with metastatic gastric cancer benefiting from combined radioimmunotherapy treatment: a case report

Persistent anti-NY-ESO-1-specific T cells and expression of differential biomarkers in a patient with metastatic gastric cancer benefiting from combined radioimmunotherapy treatment: a case report

Three Genes Predict Prognosis in Microenvironment of Ovarian Cancer

Identification of a Prognostic Gene Signature Associated with Microenvironment in Acute Myeloid Leukemia

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A nine-gene signature related to tumor microenvironment predicts overall survival with ovarian cancer

Cited by 31 publications

References 70 publications

Persistent anti-NY-ESO-1-specific T cells and expression of differential biomarkers in a patient with metastatic gastric cancer benefiting from combined radioimmunotherapy treatment: a case report

Persistent anti-NY-ESO-1-specific T cells and expression of differential biomarkers in a patient with metastatic gastric cancer benefiting from combined radioimmunotherapy treatment: a case report

Three Genes Predict Prognosis in Microenvironment of Ovarian Cancer

Identification of a Prognostic Gene Signature&nbsp;Associated with Microenvironment in&nbsp;Acute Myeloid Leukemia

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Identification of a Prognostic Gene Signature Associated with Microenvironment in Acute Myeloid Leukemia