The Clinical Significance and Prognostic Value of HER2 Expression in Bladder Cancer: A Meta-Analysis and a Bioinformatic Analysis

Gan, Kai; Gao, Yue; Liu, Kuangzheng; Xu, Bin; Qin, Weijun

doi:10.3389/fonc.2021.653491

Cited by 23 publications

(26 citation statements)

References 53 publications

(94 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The association between clinical outcomes and HER2 expression in UCB has been reported in several single-center studies; however, the overall result remains controversial. Recently, Gan et al ( 30 ) comprehensively analyzed 14 studies that included a total of 1,398 patients with BCa with regard to the HER2 status determined using IHC. They found that the overexpression of HER2 was strongly related to an advanced pathological stage, high tumor grade and tumor recurrence, but not to OS, disease-specific survival, or progression-free survival.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of HER2 status evaluation using immunohistochemistry in patients with urothelial carcinoma of the bladder: A retrospective single‑center experience

Bai

Yin

et al. 2022

Exp Ther Med

View full text Add to dashboard Cite

In recent years, antibody-drug conjugate (ADC) therapy targeting human epidermal growth factor receptor 2 (HER2) has been proven to be beneficial in patients with advanced urothelial carcinoma of the bladder (UCB); however, the role of HER2 in UCB remains obscure. Thus, the present retrospective single-center study was performed to evaluate the expression of HER2 in UCB and its prognostic significance. The HER2 status of 108 patients with UCB who underwent radical cystectomy was assessed using immunohistochemistry, and its association with the recurrence and survival rates of patients was analyzed. HER2 overexpression was observed in 57.4% of the patients; this was significantly associated with higher tumor grades (P=0.006) and stages (P<0.001). Kaplan-Meier analysis suggested that patients with HER2 overexpression had a shorter 5-year overall survival rate (P=0.005) and recurrence-free survival rate (P=0.003). Multivariate Cox regression analysis indicated that HER2 overexpression was a high-risk independent predictor of UCB recurrence (hazard ratio, 3.61; 95% confidence interval, 1.07-12.18; P=0.039). On the whole, these findings demonstrate that evaluating the HER2 status may improve the prediction of cancer recurrence and may thus guide the selection of patients that will benefit the most from HER2-ADC therapies.

show abstract

Section: Discussionmentioning

confidence: 99%

Prognostic significance of HER2 status evaluation using immunohistochemistry in patients with urothelial carcinoma of the bladder: A retrospective single‑center experience

Bai

Yin

et al. 2022

Exp Ther Med

View full text Add to dashboard Cite

show abstract

“…and ATM in bladder carcinogenesis individually. 18,46,47 Published data reported amplification of the ERBB2 gene in up to 42% and up-regulation of protein expression in up to 30% of bladder cancer cases. The same report indicated an inactivating mutation of ATM gene in 14% of bladder cancers.…”

Section: Discussionmentioning

confidence: 99%

Interaction between HER2 and ATM predicts poor survival in bladder cancer patients

Albarakati

Alshareeda

Ramadan

et al. 2022

J Cellular Molecular Medi

View full text Add to dashboard Cite

Human Epidermal Growth Factor Receptor 2 (HER2) overexpression is considered one of the interesting prognostic biomarkers in bladder cancer. However, the mechanism of bladder cancer development in relation to HER2 status remains to be elucidated. In this study, we investigated HER2‐Ataxia telangiectasia mutated (ATM) kinase interaction and their impact on patient survival and cancer aggressiveness. Using the Cancer Genome Atlas (TCGA) cohorts, we demonstrated that ATM expression (protein/mRNA) is increased in HER2 deficient compared with proficient HER2 patients. This finding was then validated using the Gene Expression Omnibus database (GEO). Correlation analysis (using low expression vs high expression as a discriminator) revealed a significant association of ATM low and HER2 high status with several clinicopathological variables such as high tumour grade, late disease stage and tumour shape. Kaplan–Meier survival analysis indicated that ATM low and HER2 high is a powerful prognosticator of both overall survival (OS) and disease‐free survival (DFS). Furthermore, using bioinformatics and protein/protein interaction analyses, we identified 66 putative overlapping proteins with direct link between HER2 and ATM most of which are functionally involved in transcription regulation, apoptotic process and cell proliferation. Interestingly, the results showed that these proteins are strongly linked with PI3K‐Akt pathway, p53 pathway and microRNAs in cancer. Altogether, our data pinpoint an important biological role of the interconnection between HER2 and ATM. The latter appear to be an independent prognostic biomarker and may serve as targets to develop novel combination therapies to improve the outcome of patients with bladder cancer.

show abstract

“…One trial (NCT03740256) combines the use of a human epidermal growth factor receptor 2 (HER2)–specific CAR T with an immunostimulatory oncolytic virus to enhance immune reactivity. HER2 has been found to be altered in bladder cancer and in a study was found to be altered in 16% of bladder tumors 62,63 . Overall, CAR T cells for the treatment of bladder cancer are in the early stages of clinical development and target antigens that are overexpressed in bladder tumors.…”

Section: Act In Bladder Cancermentioning

confidence: 97%

“…HER2 has been found to be altered in bladder cancer and in a study was found to be altered in 16% of bladder tumors. 62,63 Overall, CAR T cells for the treatment of bladder cancer are in the early stages of clinical development and target antigens that are overexpressed in bladder tumors.…”

Section: Car T Cellsmentioning

confidence: 99%

Current State of Cell Therapies for Genitourinary Malignancies

Alkhouli¹,

Bazargan²,

Pilon‐Thomas³

et al. 2022

Cancer J

View full text Add to dashboard Cite

Genitourinary (GU) cancers have greatly benefited from immunotherapy treatments, such as immune checkpoint inhibitors. However, the durable clinical response rate for these agents remains relatively low, calling for more innovative immunotherapy approaches. Adoptive cell therapy has shown a significant advancement in the treatment of cancer in recent years and represents a great potential for the treatment of GU cancers. This review summarizes the current advancements in cellular therapy strategies for the treatment of renal cell carcinoma, bladder cancer, and prostate and penile cancers. Further, current and past clinical trials of adoptive cell therapy in GU tumors are reviewed. Finally, a perspective on the future of cell therapy in GU tumors is discussed.

show abstract

The Clinical Significance and Prognostic Value of HER2 Expression in Bladder Cancer: A Meta-Analysis and a Bioinformatic Analysis

Cited by 23 publications

References 53 publications

Prognostic significance of HER2 status evaluation using immunohistochemistry in patients with urothelial carcinoma of the bladder: A retrospective single‑center experience

Prognostic significance of HER2 status evaluation using immunohistochemistry in patients with urothelial carcinoma of the bladder: A retrospective single‑center experience

Interaction between HER2 and ATM predicts poor survival in bladder cancer patients

Current State of Cell Therapies for Genitourinary Malignancies

Contact Info

Product

Resources

About