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. 2022 Nov 2:13:1047481.
doi: 10.3389/fgene.2022.1047481. eCollection 2022.

A novel signature to predict the neoadjuvant chemotherapy response of bladder carcinoma: Results from a territory multicenter real-world study

Huihuang Li  1   2 , Jiao Hu  1   2 , Xiongbing Zu  1   2 , Minfeng Chen  1   2 , Jinbo Chen  1   2 , Yihua Zou  3 , Ruoping Deng  4 , Gang Qin  4 , Wenze Li  5 , Jiansheng Tang  6 , Dingshan Deng  1   2 , Jinhui Liu  1   2 , Chunliang Cheng  1   2 , Yu Cui  1   2 , Zhenyu Ou  1   2
Affiliations

A novel signature to predict the neoadjuvant chemotherapy response of bladder carcinoma: Results from a territory multicenter real-world study

Huihuang Li et al. Front Genet. .

Abstract

Background: Although neoadjuvant chemotherapy (NAC) has become the standard treatment option for muscle invasive bladder carcinoma (MIBC), its application is still limited because of the lack of biomarkers for NAC prediction. Methods: We conducted a territory multicenter real-world study to summarize NAC practice in China and its associated clinicopathologic variables with NAC response. Then, we developed and validated a robust gene-based signature for accurate NAC prediction using weighted correlation network analysis (WGCNA), the least absolute shrinkage and selector operation (LASSO) algorithm, a multivariable binary logistic regression model, and immunohistochemistry (IHC). Results: In total, we collected 69 consecutive MIBC patients treated with NAC from four clinical centers. The application of NAC in the real world was relatively safe, with only two grade Ⅳ and seven grade Ⅲ AEs and no treatment-related deaths being reported. Among these patients, 16 patients gave up surgery after NAC, leaving 53 patients for further analysis. We divided them into pathological response and non-response groups and found that there were more patients with a higher grade and stage in the non-response group. Patients with a pathological response could benefit from a significant overall survival (OS) improvement. In addition, univariate and multivariate logistic analyses indicated that tumor grade and clinical T stage were both independent factors for predicting NAC response. Importantly, we developed and validated a five-gene-based risk score for extremely high predictive accuracy for NAC response. Conclusion: NAC was relatively safe and could significantly improve OS for MIBC patients in the real-world practice. Our five-gene-based risk score could guide personalized therapy and promote the application of NAC.

Keywords: bladder carcinoma; neoadjuvant chemotherapy; pathological response; personalized therapy; risk score.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Kaplan–Meier estimated plot comparing the overall survival of patients with pathological response and non-response groups. The red line represents the non-responsive group, while the blue line represents the responsive group.
FIGURE 2
FIGURE 2
Receiver operating characteristic curves (ROCs) of our development [(A), GSE69795] and validation [(B), GSE52219] cohorts.
FIGURE 3
FIGURE 3
Kaplan–Meier estimated plot comparing the overall survival of patients with high- and low-risk score groups. (A) GSE69795 and (B) GSE52219. The red line represents the high-risk score group, while the blue line represents the low-risk score group.
FIGURE 4
FIGURE 4
Representative images of CEP83 staining. (A) Negative staining (no response group). (B) Positive staining (response group). (C) Receiver operating characteristic curves (ROCs) of CEP83 in our IHC cohort.
See this image and copyright information in PMC

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