Immune‐related signature predicts the prognosis and immunotherapy benefit in bladder cancer

Wang, Yejinpeng; Liang, Changhong; Yu, Mengxue; Fang, Yayun; Qian, Kaiyu; Wang, Gang; Ju, Lingao; Xiao, Yu; Wang, Xinghuan

doi:10.1002/cam4.3400

“…Distinguishing the immune phenotypes of BLCA is a promising way for improving ICB response rates in BLCA. Many efforts are committing to developing a risk score for immune phenotypes (Wang et al, 2020;Liu et al, 2021), and this is the first TNF-based risk score for predicting immune phenotypes in BLCA. We not only correlated the risk score with TME immune cell infiltration in pubic databases, but also validated its role in TME using the RNA-seq cohort developed by our hospital (Xiangya cohort), which made our risk score a more robust and reliable tool for predicting immune phenotypes.…”

Section: Discussionmentioning

confidence: 99%

TNF Family–Based Signature Predicts Prognosis, Tumor Microenvironment, and Molecular Subtypes in Bladder Carcinoma

Li

¹

,

Liu

²

,

Li

³

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Background: Tumor necrosis factor (TNF) family members play vital roles in cancer development and antitumor immune responses. However, the expression patterns, prognostic values, and immunological characteristics of TNF members in bladder carcinoma (BLCA) remain unclear.Methods: The training cohort, TCGA-BLCA, was downloaded from The Cancer Genome Atlas; another two Gene Expression Omnibus datasets (GSE13507 and GSE32894) and the Xiangya cohort (RNA-sequencing cohort collected from our hospital) were used as the external validation cohort. The least absolute shrinkage and selection operator (LASSO) algorithm and cross-validation were used to screen variables. Cox regression model and random survival forest (RSF) were used to develop the risk score, respectively. Then, we systematically correlated the TNF risk score with the tumor microenvironment (TME) cell infiltration, molecular subtypes of BLCA, and the potential value for predicting the efficacy of immunotherapy.Results: We developed two TNF-based patterns, named TNF cluster 1 and TNF cluster 2. TNF cluster 1 exhibited poorer survival outcome and an inflamed TME characteristic compared with TNF cluster 2. We then filtered out 196 differentially expressed genes between the two TNF clusters and applied the LASSO algorithm and cross-validation to screen out 22 genes to build the risk score. For risk score, we found that RSF exhibited higher efficacy than the Cox regression model, and we chose the risk score developed by RSF for the following analysis. BLCA patients in the higher risk score group showed significantly poorer survival outcomes. Moreover, these results could be validated in the external validation cohorts, including the GSE13507, GSE32894, and Xiangya cohorts. Then, we systematically correlated the risk score with TME cell infiltration and found that it was positively correlated with the infiltration of a majority of immune cells. Also, a higher risk score indicated a basal subtype of BLCA. Notably, the relationship between risk score, TME cell infiltration, and molecular subtypes could be validated in the Xiangya cohort.Conclusion: We developed and validated a robust TNF-based risk score, which could predict prognostic outcomes, TME, and molecular subtypes of BLCA. However, the value of risk score predicting the efficacy of immunotherapy needs further research.

show abstract

“…Annotate gene names with their respective platform files in three cohorts. Meanwhile, we searched 200 hypoxia-related genes [ 15 ] and 2483 immune-related genes [ 16 ] in the previous references. Considering the different gene annotation of three datasets, we finally identified 1220 immune-hypoxia-related genes.…”

Section: Methodsmentioning

confidence: 99%

Derivation of a Novel CIHI in Patients with Lung Adenocarcinoma for Estimating Tumor Microenvironment and Clinical Prognosis

Zhou

¹

,

Gao

²

,

Wang

³

et al. 2021

View full text Add to dashboard Cite

An interaction between hypoxia and immunity has been confirmed in tumor tissue. However, there is no combined biomarker for diagnosis on this basis. Therefore, we developed a scoring formula based on markers of hypoxia and immunity. Firstly, the hypoxia-immune formula of lung adenocarcinoma (LUAD) was derived using LASSO-Cox regression in three cohorts from public database, and the corresponding score was calculated for each patient. The formula is as follows: combined hypoxia and immune index CIHI = LDHA expression × 0.2252 + GAPDH expression × 0.0727 + ANGPTL 4 expression × 0.0724 + VEGFC expression × 0.1911 + DKK 1 expression × 0.1355 + ADM expression × 0.0588 + BTK expression × − 0.1659 . Meanwhile, patients were divided into groups according to high and low CIHI, and expression profiles of hypoxia markers and immune markers were analyzed in different groups. CIHI was used to confirm that patients with high CIHI represented a state of hypoxiahigh-immunitylow, which had worse overall survival. We also discussed the evaluation value in the immune microenvironment and clinical application of CIHI. In conclusion, this study developed and validated a hypoxia-immune formula that can guide hypoxia modifier treatment and immunotherapy in LUAD.

show abstract

“…In addition, whether to evaluate the expression of PD-L1 in both cancer cells and immune cells or only in immune cells needs to be determined based on the future studies. Furthermore, methods other than immunohistochemistry to assess immune biomarkers, such as immune-related signature, should be tested in OSCC cases treated with immunotherapy as this method has showed a good predictive value to immunotherapy in other tumors ( 33 , 34 ).…”

Section: Progress Of Research On Immune Biomarkers Of Osccmentioning

confidence: 99%

Biomarkers for Immunotherapy of Oral Squamous Cell Carcinoma: Current Status and Challenges

Almangush

¹

,

Leivo

²

,

Mäkitie

³

2021

View full text Add to dashboard Cite

Oral squamous cell carcinoma (OSCC) forms a major health problem in many countries. For several decades the management of OSCC consisted of surgery with or without radiotherapy or chemoradiotherapy. Aiming to increase survival rate, recent research has underlined the significance of harnessing the immune response in treatment of many cancers. The promising finding of checkpoint inhibitors as a weapon for targeting metastatic melanoma was a key event in the development of immunotherapy. Furthermore, clinical trials have recently proven inhibitor of PD-1 for treatment of recurrent/metastatic head and neck cancer. However, some challenges (including patient selection) are presented in the era of immunotherapy. In this mini-review we discuss the emergence of immunotherapy for OSCC and the recently introduced biomarkers of this therapeutic strategy. Immune biomarkers and their prognostic perspectives for selecting patients who may benefit from immunotherapy are addressed. In addition, possible use of such biomarkers to assess the response to this new treatment modality of OSCC will also be discussed.

show abstract

Immune‐related signature predicts the prognosis and immunotherapy benefit in bladder cancer

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 39 publications

References 54 publications

TNF Family–Based Signature Predicts Prognosis, Tumor Microenvironment, and Molecular Subtypes in Bladder Carcinoma

TNF Family–Based Signature Predicts Prognosis, Tumor Microenvironment, and Molecular Subtypes in Bladder Carcinoma

Derivation of a Novel CIHI in Patients with Lung Adenocarcinoma for Estimating Tumor Microenvironment and Clinical Prognosis

Biomarkers for Immunotherapy of Oral Squamous Cell Carcinoma: Current Status and Challenges

Contact Info

Product

Resources

About