Inflammatory-Related Genetic Variants in Non–Muscle-Invasive Bladder Cancer Prognosis: A Multimarker Bayesian Assessment

Masson-Lecomte, A.; Maturana, Evangelina López de; Goddard, Michael E.; Picornell, Antoni C.; Rava, Marta; González‐Neira, Anna; Márquez, Mirari; Carrato, Alfredo; Tardón, Adonina; Lloreta, Josep; Silverman, Debra T.; Rothman, Nathaniel; Kogevinas, Manolis; Allory, Yves; Chanock, Stephen J.; Real, Francisco X.; Malats, Núria

doi:10.1158/1055-9965.epi-15-0894

Cited by 8 publications

(5 citation statements)

References 53 publications

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“…A total of 10 genes were identified to be correlated with overall survival. Among these identified genes, 5 genes (CALD1, HOXB3, HOXB6, MOGAT2, and TNC) have been reported to be associated with the development or prognosis of bladder cancer, indicating that the results in our study are consistent with previous publications in bladder cancer [ 29 – 31 ]. The remaining 5 genes have not been found to be associated with the prognosis of bladder cancer (BTBD16, OLFML2B, PRRX1, SPINK4, and SPON2).…”

Section: Discussionsupporting

confidence: 92%

Identification of Prognosis-Related Genes in Bladder Cancer Microenvironment across TCGA Database

Zhao

Tang

Ren

et al. 2020

BioMed Research International

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Background. Bladder cancer (BCa) is a common urothelial malignancy. The Cancer Genome Atlas (TCGA) database allows for an opportunity to analyze the relationship between gene expression and clinical outcomes in bladder cancer patients. This study is aimed at identifying prognosis-related genes in the bladder cancer microenvironment. Methods. Immune scores and stromal scores were calculated by applying the ESTIMATE algorithm. We divided bladder cancer patients into high and low groups based on their immune/stromal scores. Then, differentially expressed genes (DEGs) were identified in bladder cancer patients based on the TCGA database. We evaluated the correlation between immune/stromal scores and clinical characteristics as well as prognosis. Finally, we validated identified genes associated with bladder cancer prognosis through a cohort study in the Gene Expression Omnibus (GEO) database. Results. A higher stromal score was associated with female (vs. male p = 0.037 ), age > 65 (vs. age ≤ 65 p = 0.015 ), T3/4 (vs. T1/2, p < 0.001 ), N status p = 0.016 , and pathological high grade (vs. low grade P < 0.001 ). By analyzing DEGs, there were 1125 genes commonly upregulated, and 209 genes were commonly downregulated. Protein-protein interaction networks further showed the important protein that may be involved in the biological behavior and prognosis of BCa, such as FN1, CXCL12, CD3E, LCK, and ZAP70. A total of 14 DEGs were found to be associated with overall survival of bladder cancer. After validation by a cohort of 165 BCa cases with detailed follow-up information from GSE13507, 10 immune-associated DEGs were demonstrated to be predictive of prognosis in BCa. Among them, 5 genes have not been reported previously associated with the prognosis of BCa, including BTBD16, OLFML2B, PRRX1, SPINK4, and SPON2. Conclusions. Our study elucidated tight associations between stromal score and clinical characteristics as well as prognosis in BCa. Moreover, we obtained a group of genes closely related to the prognosis of BCa in the tumor microenvironment.

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Section: Discussionsupporting

confidence: 92%

Identification of Prognosis-Related Genes in Bladder Cancer Microenvironment across TCGA Database

Zhao

Tang

Ren

et al. 2020

BioMed Research International

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“…This protein may be involved in cell growth and differentiation and it is known as a negative regulator of T-and B-cell receptor signaling. Its expression has been shown to be implicated in T lymphocytes tolerance toward tumor cells [49]. In contrast we have found that genetic variations in BLNK (rs3789928), TP63 (rs710521), ROCK1 (rs288980) and ACTRT3/MYNN (rs10936599) were associated with a decreased risk of bladder cancer.…”

Section: Others Cellular Pathwaymentioning

confidence: 63%

Development of a Custom NGS Panel for the Determination of Bladder Cancer Risk

Hemissi

Bousetta

Dallali

et al. 2021

Preprint

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BackgoundBladder cancer (BCa) is a heterogeneous disease caused by the interaction between environmental and genetic risk factors. The objective of this study was to design a panel that evaluates the role of some selected variants in BCa susceptibility. We are also interested in studying the interaction between environmental and genetic risk factors.MethodsThe case/controls cohort was composed with 249 BCa cases and 255 controls. The designed Bladder cancer hereditary panel (BCHP) is composed of 139 selected variants. These variants were genotyped by an amplification-based targeted Next-Generation Sequencing (NGS) on the Ion Torrent Proton sequencer (Life Technologies, Ion Torrent technology). ResultsWe have found that rs162555, rs2228000, rs10936599, rs710521, rs3752645, rs804276, rs4639, rs4881400 and rs288980 were significantly associated with decreased risk of bladder cancer. However the homozygous genotypes for VPS37C (rs7104333, A/A), MPG (rs1013358, C/C) genes or the heterozygous genotype for ARNT gene (rs1889740, rs2228099, rs2256355, rs2864873), GSTA4 (rs17614751) and APOBR/IL27 (rs17855750) were significantly associated with increased risk of bladder cancer development compared to reference group (OR=2.53, 2.34, 1.99, 2.00, 2.00, 1.47, 1.96 and 2.27 respectively). We have also found that non–smokers patients harboring heterozygous genotypes for ARNT/rs2864873 (A>G), ARNT/ rs1889740 (C>T) or GSTA4/rs17614751 (G to A) were respectively at 2.775, 3.069 and 6.608 –folds increased risk of Bca development compared to non-smokers controls with wild genotypes. Moreover the ARNT CT (rs1889740), ARNT CG (rs2228099), ARNT TC (rs2864873) and GSS GA genotypes were associated with an increased risk of BCa even in absence of professional risk factors. Finally the decision-tree analysis produced a three major BCa class. These three classes were essentially characterized by an intensity of tobacco use more than 20 pack years (PY) and the CYP1A2 (rs762551) genotype. ConclusionsThe determined association between genetic variations in BCa and environmental factors, as well as the effect of studied pathway SNPs in comparison with environmental exposition may provide urologists additional genetic information that may help for clinical assessment and treatment decisions. Nevertheless, the underlying mechanisms through which these genes or SNPs affect the clinical behavior of BCas require further studies.

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“…Previous studies have reported that inflammation-associated genes risk signature can be used to predict patient prognosis and guide treatment for esophageal squamous cell carcinoma, lung adenocarcinoma and urothelial bladder cancer. [28][29][30][31] Other hand, Sia et al determined that inflammation response-related gene signature could be correlated with the immune exhausted. 32 Many cancers are characterized by simultaneous immunosuppression and inflammation, their regulation is integrally linked, which can induce a dysfunctional immune state unable to eliminate disease.…”

Section: Discussionmentioning

confidence: 99%

A Novel Gene Signature Associated with Inflammatory Responses and Immune Status Assists in Prognosis and Intervention for Patients with HCC

Lu¹,

Du²,

Feng³

et al. 2022

JIR

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Background Tumor growth depends on tumor cells and the tumor microenvironment, which are regulated by inflammation and immune responses. However, the roles of inflammation and immune status in hepatocellular carcinoma (HCC) remain unclear. The aim of this study was to evaluate the prognostic value of an inflammatory response- related gene signature associated with immune status, which may provide insight into new treatment options for HCC patients. Materials and Methods Differentially expressed genes associated with inflammation were obtained from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus, and the Molecular Signatures Database. An inflammation-associated prognostic gene signature was constructed and validated using TCGA and the International Cancer Genome Consortium datasets, respectively, using LASSO Cox regression analysis. Log-rank was performed to compare the overall survival of low- and high-risk score cohorts. Immune cell infiltration and immune-related functions were analyzed using single-sample gene enrichment analysis. The structures of the drugs identified by the prognostic model were predicted using PubChem. The drugs sensitivity of bleomycin, simvastatin and zoledronate detected by CCK8 colorimetric assay. The mRNA levels of 7 genes in HCC after drug treatment analyzed via qRT-PCR. Results Inflammation-associated genes, including ITGA5, MEP1A, P2RX4, RIPK2, SLC7A1 and SRI, were identified and found to be associated with the prognosis of HCC. We further found that the high-risk patients experienced poor prognosis, which was observed to be an independent and significant risk factor for prognosis. Moreover, we observed elevated expression levels in multiple immune cell types and immune function. Lastly, we validated that bleomycin, simvastatin and zoledronate could regulate these genes in HCC. Conclusion The inflammatory-response-associated gene signature could predict the prognosis and the immunological status of HCC patients. Additionally, bleomycin, simvastatin and zoledronate may represent potential drug candidates that could inhibit these genes. This may constitute a new approach for the treatment of HCC.

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Inflammatory-Related Genetic Variants in Non–Muscle-Invasive Bladder Cancer Prognosis: A Multimarker Bayesian Assessment

Cited by 8 publications

References 53 publications

Identification of Prognosis-Related Genes in Bladder Cancer Microenvironment across TCGA Database

Identification of Prognosis-Related Genes in Bladder Cancer Microenvironment across TCGA Database

Development of a Custom NGS Panel for the Determination of Bladder Cancer Risk

A Novel Gene Signature Associated with Inflammatory Responses and Immune Status Assists in Prognosis and Intervention for Patients with HCC

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