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Prognostic and Predictive Value of O6-methylguanine Methyltransferase for Chemotherapy in Patients with Muscle-Invasive Bladder Cancer

  • Urologic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Purpose

DNA repair genes are potential biomarkers for chemotherapy in muscle-invasive bladder cancer (MIBC). O6-methylguanine methyltransferase (MGMT) is involved in DNA repair and is found to affect the efficacy of platinum-based chemotherapy. However, the prognostic or predictive value of MGMT expression in chemotherapy for MIBC is unknown.

Materials and Methods

Immunohistochemical staining for MGMT was performed in paraffin-embedded tumor tissue of high-grade MIBC patients who underwent cystectomy in two independent cohorts [n = 74 for Fudan University Shanghai Cancer Center (FUSCC) cohort and n = 115 for Zhongshan Hospital (ZS) cohort]. MGMT messenger RNA (mRNA) analysis was conducted using patients’ clinical and fragments per kilobase of exon model per million mapped fragments mRNA data from The Cancer Genome Atlas (TCGA) database (n = 245).

Results

In our cohorts, high MGMT expression was significantly correlated with shorter overall survival (OS) in patients with platinum-based adjuvant chemotherapy [hazard ratio (HR) 2.386, p = 0.048; HR 2.920, p = 0.007; HR 2.324, p = 0.004, respectively, in FUSCC, ZS, and combination sets], but not in patients without chemotherapy. These findings were corroborated by the TCGA set (HR 1.952 and 0.697 for patients with and without chemotherapy, respectively). The chemotherapy–MGMT interaction for OS was significant in both the surgery set (p = 0.045) and TCGA set (p = 0.034).

Conclusions

We demonstrated that high MGMT expression is an independent poor prognostic factor in MIBC patients with platinum-based adjuvant chemotherapy, but not in patients without chemotherapy. MGMT expression may be a potential predictor for administration of adjuvant chemotherapy.

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Acknowledgment

The results shown here are in part based upon data generated by the TCGA Research Network (http://cancergenome.nih.gov/). The authors thank TCGA Research Network for original data, and Huaipeng Zhang (Facebook Inc., California) for his program to extract data from the TCGA website. This study was funded by grants from National Natural Science Foundation of China (81402082, 81472227 and 31770851), Shanghai Municipal Commission of Health and Family Planning Program (20144Y0223), Innovation Project of Shanghai Jiao Tong University School of Medicine (16XJ21003), Outstanding Young Talent Training Plan of Shanghai Municipal Commission of Health and Family Planning (no. XYQ2013102), Guide Project of Science and Technology Commission of Shanghai Municipality (no. 17411963100), and a grant from Shanghai Cancer Research Charity Center. All these study sponsors played no role in the study design or collection, analysis, and interpretation of data.

Author Contributions

Conception and design: JZ, YZ, YW, BD, JX. Development of methodology: JZ, YZ, YW, QF, HX, ZL, HF, YC. Acquisition of data: JZ, YZ, YW, HX, ZL. Analysis and interpretation of data: JZ, YZ, YW, BD, JX. Writing, review, and/or revision of the manuscript: JZ, YZ, YW, QF, BD, JX. Administrative, technical, or material support: QF, HX, ZL, HF, YC. Study supervision: BD, JX

Conflict of interest

The authors declare no conflicts of interest.

Author information

Author notes

  1. Junyu Zhang, Yu Zhu, and Yiwei Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China

    Junyu Zhang MD, Yu Zhu MD, Huyang **e MD, Zheng Liu MD, Hangcheng Fu MD & Bo Dai MD

  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

    Junyu Zhang MD, Yu Zhu MD, Huyang **e MD, Zheng Liu MD, Hangcheng Fu MD & Bo Dai MD

  3. Department of Urology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Yiwei Wang MD

  4. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China

    Qiang Fu PhD, Yifan Cao MD & Jiejie Xu MD, PhD

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  1. Junyu Zhang MD
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  2. Yu Zhu MD
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Correspondence to Jiejie Xu MD, PhD or Bo Dai MD.

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Zhang, J., Zhu, Y., Wang, Y. et al. Prognostic and Predictive Value of O6-methylguanine Methyltransferase for Chemotherapy in Patients with Muscle-Invasive Bladder Cancer. Ann Surg Oncol 25, 342–348 (2018). https://doi.org/10.1245/s10434-017-6145-3

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