A Novel Immune-Gene Pair Signature Revealing the Tumor Microenvironment Features and Immunotherapy Prognosis of Muscle-Invasive Bladder Cancer

Immunotherapy has been a milestone for muscle-invasive bladder cancer (MIBC), but only a small portion of patients can benefit from it. Therefore, it is crucial to develop a robust individualized immune-related signature of MIBC to identify patients potentially benefiting from immunotherapy. The current study identified patients from the Cancer Genome Atlas (TCGA) and immune genes from the ImmPort database, and used improved data analytical methods to build up a 45 immune-related gene pair signature, which could classify patients into high-risk and low-risk groups. The signature was then independently validated by a Gene Expression Omnibus (GEO) dataset and IMvigor210 data. The subsequent analysis confirmed the worse survival outcomes of the high-risk group in both training (p < 0.001) and validation cohorts (p = 0.018). A signature-based risk score was proven to be an independent risk factor of overall survival (p < 0.001) and could predict superior clinical net benefit compared to other clinical factors. The CIBERSORT algorithm revealed the low-risk group had increased CD8+ T cells plus memory-activated CD4+ T-cell infiltration. The low-risk group also had higher expression of PDCD1 (PD-1), CD40, and CD27, and lower expression of CD276 (B7-H3) and PDCD1LG2 (PD-L2). Importantly, IMvigor210 data indicated that the low-risk group had higher percentage of “inflamed” phenotype plus less “desert” phenotype, and the survival outcomes were significantly better for low-risk patients after immunotherapy (p = 0.014). In conclusion, we proposed a novel and promising prognostic immune-related gene pair (IRGP) signature of MIBC, which could provide us a panoramic view of the tumor immune microenvironment of MIBC and independently identify MIBC patients who might benefit from immunotherapy.

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Recurrence and progression of non-muscle invasive bladder cancer following trans-urethral resection of bladder tumour with adjuvant intravesical chemo-immunotherapy

Journal of Chitwan Medical College ◽

10.3126/jcmc.v10i3.32035 ◽

2020 ◽

Vol 10 (3) ◽

pp. 34-38

Author(s):

Ashok Kumar Kunwar ◽

Kabir Tiwari ◽

Sanjesh Bhakta Shrestha ◽

Srijana Thapa ◽

Ashish Kumar Panthee ◽

...

Keyword(s):

Bladder Cancer ◽

High Risk ◽

Effective Treatment ◽

Risk Group ◽

Bladder Tumour ◽

Low Risk ◽

Invasive Bladder Cancer ◽

Intermediate Risk ◽

Muscle Invasive Bladder Cancer ◽

Muscle Invasive

Background: Trans-urethral resection of bladder tumor is an essential diagnostic tool as well as effective treatment modality for non-muscle invasive bladder cancer. We aimed to evaluate the recurrence and progression of the non-muscle invasive bladder cancer in Nepalese patients. Methods: This was a retrospective study of 43 patients with non-muscle invasive bladder cancer, who underwent trans-urethral resection of bladder tumour followed by adjuvant intravesical instillation of chemo or immunotherapy between January, 2013 to December, 2018. Patients were divided into low, intermediate and high-risk groups according to the clinical and pathological factors used by the European Organization for Research and Treatment of Cancer scoring system. Outcomes were calculated in terms of recurrence and progression in each group. Results: Out of 43 patients, 11 (25.58%) patients had low risk, 18 (41.86%) patients had intermediate risk and 14 (32.56%) patients had high risk of recurrence categories. No recurrence and progression of the disease noted in low risk group. In the intermediate risk group, out of 18 patients, 4 (22.2%) patients developed recurrence and 2 (11.1%) patients had progression of disease. In high risk group, out of 14 patients, 4 (26.8%) patients developed recurrence and 2 (14%) patients developed progression of the disease. Conclusions: Even in a low volume centre of bladder cancer, effective treatment for non-muscle invasive bladder cancer with trans-urethral resection of bladder tumour followed by adjuvant intravesical chemo or immunotherapy can be given safely to reduce recurrence and progression of the disease.

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Systematic analysis of gene expression profiles reveals prognostic stratification and underlying mechanisms for muscle-invasive bladder cancer

Cancer Cell International ◽

10.1186/s12935-019-1056-y ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Ping-Bao Zhang ◽

Zi-Li Huang ◽

Yong-Hua Xu ◽

Jin Huang ◽

Xin-Yu Huang ◽

...

Keyword(s):

Bladder Cancer ◽

High Risk ◽

Risk Prediction ◽

Risk Group ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Gene Signatures ◽

Muscle Invasive ◽

Multiple Drugs ◽

Worse Prognosis

Abstract Background Muscle-invasive bladder cancer (MIBC) is originated in the muscle wall of the bladder, and is the ninth most common malignancy worldwide. However, there are no reliable, accurate and robust gene signatures for MIBC prognosis prediction, which is of the importance in assisting oncologists to make a more accurate evaluation in clinical practice. Methods This study used univariable and multivariable Cox regression models to select gene signatures and build risk prediction model, respectively. The t-test and fold change methods were used to perform the differential expression analysis. The hypergeometric test was used to test the enrichment of the differentially expressed genes in GO terms or KEGG pathways. Results In the present study, we identified three prognostic genes, KLK6, TNS1, and TRIM56, as the best subset of genes for muscle-invasive bladder cancer (MIBC) risk prediction. The validation of this stratification method on two datasets demonstrated that the stratified patients exhibited significant difference in overall survival, and our stratification was superior to three other stratifications. Consistently, the high-risk group exhibited worse prognosis than low-risk group in samples with and without lymph node metastasis, distant metastasis, and radiation treatment. Moreover, the upregulated genes in high-risk MIBC were significantly enriched in several cancer-related pathways. Notably, PDGFRB, a receptor for platelet-derived growth factor of PI3K-Akt signaling pathway, and TUBA1A were identified as two targets of multiple drugs. In addition, the angiogenesis-related genes, as well as two marker genes of M2 macrophage, CD163 and MRC1, were highly upregulated in high-risk MIBC. Conclusions In summary, this study investigated the underlying molecular mechanism and potential therapeutic targets associated with worse prognosis of high-risk MIBC, which could improve our understanding of progression of MIBC and provide new therapeutic strategies for the MIBC patients.

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Establishment of Immune-related Gene Pair Signature to Predict Lung Adenocarcinoma Prognosis

Cell Transplantation ◽

10.1177/0963689720977131 ◽

2020 ◽

Vol 29 ◽

pp. 096368972097713

Author(s):

Xueping Jiang ◽

Yanping Gao ◽

Nannan Zhang ◽

Cheng Yuan ◽

Yuan Luo ◽

...

Keyword(s):

High Risk ◽

Lung Adenocarcinoma ◽

Gene Pair ◽

Risk Group ◽

High Risk Group ◽

Gene Set Enrichment Analysis ◽

M2 Macrophage ◽

Related Gene ◽

Immune Related Gene ◽

Potential Biomarker

Tumor microenvironment (TME) has critical impacts on the pathogenesis of lung adenocarcinoma (LUAD). However, the molecular mechanism of TME effects on the prognosis of LUAD patients remains unclear. Our study aimed to establish an immune-related gene pair (IRGP) model for prognosis prediction and internal mechanism investigation. Based on 702 TME-related differentially expressed genes (DEGs) extracted from The Cancer Genome Atlas (TCGA) training cohort using the ESTIMATE algorithm, a 10-IRGP signature was established to predict LUAD patient prognosis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that DEGs were significantly associated with tumor immune response. In both TCGA training and Gene Expression Omnibus validation datasets, the risk score was an independent prognostic factor for LUAD patients using Lasso-Cox analysis, and patients in the high-risk group had poorer prognosis than those in the low-risk one. In the high-risk group, M2 macrophage and neutrophil infiltrations were higher, while the levels of T cell follicular helpers were significantly lower. The gene set enrichment analysis results showed that DNA repair signaling pathways were involved. In summary, we established an IRGP signature as a potential biomarker to predict the prognosis of LUAD patients.

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Validation of an Immune-related Gene Pair Index as a Prognostic Marker of Early-Stage Lung Squamous Cell Carcinoma

10.21203/rs.3.rs-32984/v1 ◽

2020 ◽

Author(s):

Zihao Wang ◽

Xuan Xiang ◽

Xiaoshan Wei ◽

Linlin Ye ◽

Yiran Niu ◽

...

Keyword(s):

High Risk ◽

Validation Cohort ◽

Risk Group ◽

Early Stage ◽

Lung Squamous Cell Carcinoma ◽

High Risk Group ◽

Low Risk ◽

Data Sets ◽

Related Gene ◽

Immune Related Gene

Abstract Background. Lung squamous cell carcinoma (LUSC) is one of the subtypes of non-small-cell lung cancer (NSCLC) and accounts for approximately 20 to 30% of all lung cancers.Methods. In this study, we developed an immune-related gene pair index (IRGPI) for early-stage LUSC from 3 public LUSC data sets, including The Cancer Genome Atlas LUSC cohort and Gene Expression Omnibus data sets, and explored whether IRGPI could act as a prognostic marker to identify patients with early-stage LUSC at high risk.Results. IRGPI was constructed by 68 gene pairs consisting of 123 unique immune-related genes from TCGA LUSC cohort. In the derivation cohort, the hazard of death among high-risk group was 10.51 times that of the low-risk group (HR, 10.51; 95%CI, 6.96-15.86; p<0.001). The hazard of death among the high-risk group was 2.26 times that of the low-risk group (HR, 2.26; 95%CI, 1.2-4.25; p=0.009) in the GSE37745 validation cohort and was 3.2 times that of low-risk group (HR, 3.2; 95%CI, 0.98-10.4; p=0.042) in the GSE41271 validation cohort. The infiltrations of CD8+ T cells and T follicular helper cells were lower in the high-risk group, as compared with the low-risk group in the TCGA cohort (6.94% vs 9.63%, p=0.004; 2.15% vs 3%, p=0.002, respectively). The infiltrations of neutrophils, activated mast cells and monocytes were higher in the high-risk group, as compared with the low-risk group in the TCGA cohort (1.63% vs 0.72%, p=0.001; 1.64% vs 1.02%, p=0.007; 0.57% vs 0.35%, p=0.041, respectively).Conclusions. IRGPI is a significant prognostic biomarker for predicting overall survival in early-stage LUSC patients.

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Prognostic Implications of Immune-Related Gene Pairs Signatures in Bladder Cancer

Journal of Oncology ◽

10.1155/2021/5345181 ◽

2021 ◽

Vol 2021 ◽

pp. 1-20

Author(s):

Hui Xiong ◽

Hui Gao ◽

Jinding Hu ◽

Yun Dai ◽

Hanbo Wang ◽

...

Keyword(s):

Bladder Cancer ◽

High Risk ◽

Risk Score ◽

Immune Cells ◽

Low Risk ◽

Gene Set Enrichment Analysis ◽

Risk Scores ◽

Related Gene ◽

Gene Pairs ◽

Immune Related Gene

Compelling evidence indicates that immune function is correlated with the prognosis of bladder cancer (BC). Here, we aimed to develop a clinically translatable immune-related gene pairs (IRGPs) prognostic signature to estimate the overall survival (OS) of bladder cancer. From the 251 prognostic-related IRGPs, 37 prognostic-related IRGPs were identified using LASSO regression. We identified IRGPs with the potential to be prognostic markers. The established risk scores divided BC patients into high and low risk score groups, and the survival analysis showed that risk score was related to OS in the TCGA-training set ( p < 0.001 ; HR = 7.5 [5.3, 10]). ROC curve analysis showed that the AUC for the 1-year, 3-year, and 5-year follow-up was 0.820, 0.883, and 0.879, respectively. The model was verified in the TCGA-testing set and external dataset GSE13507. Multivariate analysis showed that risk score was an independent prognostic predictor in patients with BC. In addition, significant differences were found in gene mutations, copy number variations, and gene expression levels in patients with BC between the high and low risk score groups. Gene set enrichment analysis showed that, in the high-risk score group, multiple immune-related pathways were inhibited, and multiple mesenchymal phenotype-related pathways were activated. Immune infiltration analysis revealed that immune cells associated with poor prognosis of BC were upregulated in the high-risk score group, whereas immune cells associated with a better prognosis of BC were downregulated in the high-risk score group. Other immunoregulatory genes were also differentially expressed between high and low risk score groups. A 37 IRGPs-based risk score signature is presented in this study. This signature can efficiently classify BC patients into high and low risk score groups. This signature can be exploited to select high-risk BC patients for more targeted treatment.

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Establishment of an immune-related gene pair model to predict colon adenocarcinoma prognosis

BMC Cancer ◽

10.1186/s12885-020-07532-7 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Jihang Luo ◽

Puyu Liu ◽

Leibo Wang ◽

Yi Huang ◽

Yuanyan Wang ◽

...

Keyword(s):

Colon Cancer ◽

High Risk ◽

Gene Pair ◽

Risk Group ◽

Colon Adenocarcinoma ◽

High Risk Group ◽

High Morbidity ◽

Related Gene ◽

Immune Genes ◽

Immune Related Gene

Abstract Background Colon cancer is the most common type of gastrointestinal cancer and has high morbidity and mortality. Colon adenocarcinoma (COAD) is the main pathological type of colon cancer, and much evidence has supported the correlation between the prognosis of COAD and the immune system. The current study aimed to develop a robust prognostic immune-related gene pair (IRGP) model to estimate the overall survival of patients with COAD. Methods The gene expression profiles and clinical information of patients with colon adenocarcinoma were obtained from the TCGA and GEO databases and were divided into training and validation cohorts. Immune genes were selected that showed a significant association with prognosis. Results Among 1647 immune genes, a model with 17 IRGPs was built that was significantly associated with OS in the training cohort. In the training and validation datasets, the IRGP model divided patients into the high-risk group and low-risk group, and the prognosis of the high-risk group was significantly worse (P<0.001). Univariate and multivariate Cox proportional hazard analyses confirmed the feasibility of this model. Functional analysis confirmed that multiple tumor progression and stem cell growth-related pathways were upregulated in the high-risk groups. Regulatory T cells and macrophages M0 were significantly highly expressed in the high-risk group. Conclusion We successfully constructed an IRGP model that can predict the prognosis of COAD, providing new insights into the treatment strategy of COAD.

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Advancements in Intravesical Chemotherapy in Non-Muscle Invasive Bladder cancer

10.5772/intechopen.99441 ◽

2021 ◽

Author(s):

Ankur Mittal ◽

Vikas Kumar Panwar ◽

Gurpremjit Singh

Keyword(s):

Bladder Cancer ◽

High Risk ◽

Low Risk ◽

Intravesical Chemotherapy ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Risk Patients ◽

Bcg Failure ◽

Significant Stage ◽

Muscle Invasive

The treatment for non-muscle-invasive bladder cancer is transurethral resection of bladder cancer followed by intravesical chemotherapy or BCG. There have been various advancements in low risk, intermediate risk, high risk, and BCG failure cases of non-muscle invasive bladder cancer. There has been increased research on hyperthermia and intravesical chemotherapy, new agents like apaziquone, use of gemcitabine in low-risk cases, and combination chemotherapy in cases of BCG failure. Combining docetaxel and gemcitabine has taken a significant stage because of BCG shortage in some parts of the world. This chapter will discuss the latest advancements in intravesical chemotherapy in low, intermediate, and high-risk patients.

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An Immune-Related Gene Pairs Signature Predicts Overall Survival in Melanoma

10.21203/rs.3.rs-386263/v1 ◽

2021 ◽

Author(s):

Ding Pan ◽

Qi-Feng Ou ◽

Pan-Feng Wu ◽

Fang Yu ◽

Ju-Yu Tang

Keyword(s):

Overall Survival ◽

High Risk ◽

Risk Group ◽

High Risk Group ◽

Low Risk ◽

Related Gene ◽

Immune Genes ◽

Gene Pairs ◽

Immune Related Gene ◽

Public Data

Abstract Background:The incidence rate and mortality rate of melanoma have been increasing in recent decades. Increasing evidence has depicted the correlation between melanoma prognosis and immune signature. Therefore, the aim of this study is to develop a robust prognostic immune-related gene pairs (IRGPs) signature for estimating overall survival (OS) of melanoma.Methods:Gene expression profiling and clinical information of melanoma patients were derived from two public data sets, divided into training and validation cohorts. Immune genes significantly associated with prognosis were selected. Results:Among 1,646 immune genes, a 25 IRGPs signature was built which was significantly associated with OS in the training cohort (P=1.80×10−22; hazard ratio [HR] =9.50 [6.04, 14.93]). In the validation datasets, the IRGPs signature significantly divided patients into high- vs low- risk groups considering their prognosis (P=2.47×10−4; HR =2.99 [1.66, 5.38]) and was prognostic in multivariate analysis. Functional analysis showed that several biological processes, including keratinization and pigment phenotype-related pathways, enriched in the high-risk group. Macrophages M0, NK cells resting and T cells gamma delta were significantly higher in the high-risk group compared with the low-risk group. Conclusions:We successfully constructed a robust IRGPs signature with prognostic values for melanoma, providing new insights into post-operational treatment strategies.

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