Gene Signature of m <sup>6</sup>A regulators in Bladder Cancer: Prognostic Significance and Immune Implication

301 Background: Hypoxia modification improves overall survival (OS) in muscle invasive bladder cancer (MIBC) patients treated with radical radiotherapy. There is evidence that hypoxic tumours benefit most from hypoxia modification. The study aimed to identify or derive a hypoxia gene signature that predicts benefit from hypoxia-modifying treatment in MIBC. Methods: Bladder cancer transcriptomic data were available from public datasets and generated for 152 tumour samples from the BCON phase III trial of radiotherapy (RT) alone or RT with carbogen and nicotinamide (CON) using Affymetrix Human 1.0 Exon ST arrays. Published hypoxia signatures were tested. A novel signature was then derived by identifying candidate hypoxia genes from the literature and evaluating their bladder cancer specificity in the publically available datasets. A gene co-expression network was built and hub genes identified to generate a signature. Results: None of the published hypoxia signatures were prognostic in public datasets or predicted benefit from hypoxia modification in the BCON patients. A novel 24-gene signature was derived and its prognostic significance was validated in 7 surgical cohorts. The signature was then independently validated in BCON patients. Patients categorised as high- versus low-hypoxia by the signature had a poor local progression free survival (LPFS) following radiotherapy alone (HR 2.37, 95% CI 1.26-4.47, P= 0.0076). The signature also predicted benefit from CON with high-hypoxia patients receiving CON having a better LPFS than those receiving radiotherapy alone (HR 0.47, 95% CI 0.26-0.86, P= 0.0147). Prognostic and predictive significance remained after adjusting for clinicopathological variables (including gender, necrosis, age, stage and carcinoma in situ). Conclusions: A 24-gene hypoxia signature has strong, independent prognostic and predictive value with the potential for stratifying patients with MIBC for treatment with hypoxia-modification strategies.

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A 10-gene prognostic signature points to LIMCH1 and HLA-DQB1 as important players in aggressive cervical cancer disease

British Journal of Cancer ◽

10.1038/s41416-021-01305-0 ◽

2021 ◽

Author(s):

Mari K. Halle ◽

Marte Sødal ◽

David Forsse ◽

Hilde Engerud ◽

Kathrine Woie ◽

...

Keyword(s):

Cervical Cancer ◽

Primary Tumour ◽

Treatment Options ◽

Prognostic Significance ◽

Gene Signature ◽

Prognostic Impact ◽

Cancer Disease ◽

Gene Set ◽

Patient Cohort ◽

Protein Levels

Abstract Background Advanced cervical cancer carries a particularly poor prognosis, and few treatment options exist. Identification of effective molecular markers is vital to improve the individualisation of treatment. We investigated transcriptional data from cervical carcinomas related to patient survival and recurrence to identify potential molecular drivers for aggressive disease. Methods Primary tumour RNA-sequencing profiles from 20 patients with recurrence and 53 patients with cured disease were compared. Protein levels and prognostic impact for selected markers were identified by immunohistochemistry in a population-based patient cohort. Results Comparison of tumours relative to recurrence status revealed 121 differentially expressed genes. From this gene set, a 10-gene signature with high prognostic significance (p = 0.001) was identified and validated in an independent patient cohort (p = 0.004). Protein levels of two signature genes, HLA-DQB1 (n = 389) and LIMCH1 (LIM and calponin homology domain 1) (n = 410), were independent predictors of survival (hazard ratio 2.50, p = 0.007 for HLA-DQB1 and 3.19, p = 0.007 for LIMCH1) when adjusting for established prognostic markers. HLA-DQB1 protein expression associated with programmed death ligand 1 positivity (p < 0.001). In gene set enrichment analyses, HLA-DQB1high tumours associated with immune activation and response to interferon-γ (IFN-γ). Conclusions This study revealed a 10-gene signature with high prognostic power in cervical cancer. HLA-DQB1 and LIMCH1 are potential biomarkers guiding cervical cancer treatment.

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Prognostic significance of bladder neck involvement in non‐muscle‐invasive bladder cancer: A SEER database analysis with 19,919 patients

Cancer Medicine ◽

10.1002/cam4.4219 ◽

2021 ◽

Author(s):

Xiangpeng Zhan ◽

Ju Guo ◽

Luyao Chen ◽

Wen Deng ◽

Xiaoqiang Liu ◽

...

Keyword(s):

Bladder Cancer ◽

Bladder Neck ◽

Prognostic Significance ◽

Invasive Bladder Cancer ◽

Seer Database ◽

Database Analysis ◽

Muscle Invasive Bladder Cancer ◽

Muscle Invasive

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Construction of an immune‐related LncRNA signature with prognostic significance for bladder cancer

Journal of Cellular and Molecular Medicine ◽

10.1111/jcmm.16494 ◽

2021 ◽

Author(s):

Wen‐Jie Luo ◽

Xi Tian ◽

Wen‐Hao Xu ◽

Yuan‐Yuan Qu ◽

Wen‐Kai Zhu ◽

...

Keyword(s):

Bladder Cancer ◽

Prognostic Significance

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A stemness-based eleven-gene signature correlates with the clinical outcome of hepatocellular carcinoma

BMC Cancer ◽

10.1186/s12885-021-08351-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Liang Hong ◽

Yu Zhou ◽

Xiangbang Xie ◽

Wanrui Wu ◽

Changsheng Shi ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cox Regression ◽

Molecular Subtypes ◽

Prognostic Significance ◽

Predictive Performance ◽

Gene Signature ◽

The Cancer Genome Atlas ◽

Cumulative Distribution ◽

Gene Module ◽

Expression Levels

Abstract Background Cumulative evidences have been implicated cancer stem cells in the tumor environment of hepatocellular carcinoma (HCC) cells, whereas the biological functions and prognostic significance of stemness related genes (SRGs) in HCC is still unclear. Methods Molecular subtypes were identified by cumulative distribution function (CDF) clustering on 207 prognostic SRGs. The overall survival (OS) predictive gene signature was developed, internally and externally validated based on HCC datasets including The Cancer Genome Atlas (TCGA), GEO and ICGC datasets. Hub genes were identified in molecular subtypes by protein-protein interaction (PPI) network analysis, and then enrolled for determination of prognostic genes. Univariate, LASSO and multivariate Cox regression analyses were performed to assess prognostic genes and construct the prognostic gene signature. Time-dependent receiver operating characteristic (ROC) curve, Kaplan-Meier curve and nomogram were used to assess the performance of the gene signature. Results We identified four molecular subtypes, among which the C2 subtype showed the highest SRGs expression levels and proportions of immune cells, whereas the worst OS; the C1 subtype showed the lowest SRGs expression levels and was associated with most favorable OS. Next, we identified 11 prognostic genes (CDX2, PON1, ADH4, RBP2, LCAT, GAL, LPA, CYP19A1, GAST, SST and UGT1A8) and then constructed a prognostic 11-gene module and validated its robustness in all three datasets. Moreover, by univariate and multivariate Cox regression, we confirmed the independent prognostic ability of the 11-gene module for patients with HCC. In addition, calibration analysis plots indicated the excellent predictive performance of the prognostic nomogram constructed based on the 11-gene signature. Conclusions Findings in the present study shed new light on the role of stemness related genes within HCC, and the established 11-SRG signature can be utilized as a novel prognostic marker for survival prognostication in patients with HCC.

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MAIT cells regulate NK cell-mediated tumor immunity

Nature Communications ◽

10.1038/s41467-021-25009-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Emma V. Petley ◽

Hui-Fern Koay ◽

Melissa A. Henderson ◽

Kevin Sek ◽

Kirsten L. Todd ◽

...

Keyword(s):

Nk Cells ◽

Tumor Immunity ◽

Nk Cell ◽

Prognostic Significance ◽

Human Tumor ◽

Gene Signature ◽

Mouse Tumor ◽

Mait Cells ◽

Mait Cell

AbstractThe function of MR1-restricted mucosal-associated invariant T (MAIT) cells in tumor immunity is unclear. Here we show that MAIT cell-deficient mice have enhanced NK cell-dependent control of metastatic B16F10 tumor growth relative to control mice. Analyses of this interplay in human tumor samples reveal that high expression of a MAIT cell gene signature negatively impacts the prognostic significance of NK cells. Paradoxically, pre-pulsing tumors with MAIT cell antigens, or activating MAIT cells in vivo, enhances anti-tumor immunity in B16F10 and E0771 mouse tumor models, including in the context of established metastasis. These effects are associated with enhanced NK cell responses and increased expression of both IFN-γ-dependent and inflammatory genes in NK cells. Importantly, activated human MAIT cells also promote the function of NK cells isolated from patient tumor samples. Our results thus describe an activation-dependent, MAIT cell-mediated regulation of NK cells, and suggest a potential therapeutic avenue for cancer treatment.

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