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High expression of CETN2 is associated with platinum resistance and poor prognosis in epithelial ovarian cancer

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Abstract

Purpose

The poor prognosis of ovarian cancer is largely due to platinum resistance. It has been demonstrated that nucleotide excision repair (NER) involving centrin-2(CETN2) is connected to platinum resistance in ovarian cancer. The molecular mechanism of CETN2 in ovarian cancer and the mechanism affecting the outcome of chemotherapy are unknown.

Methods

The protein–protein interaction (PPI) network was mapped after obtaining the interacting proteins of CETN2, and the interacting genes were subjected to enrichment analysis. To examine the relationship between CETN2 and platinum resistance, gene microarray data and clinical data related to platinum resistance in ovarian cancer were downloaded. The possible signaling pathway of CETN2 was investigated by Gene set enrichment analysis (GSEA). Immune infiltration analysis was performed. Immunohistochemistry (IHC) and quantitative real-time PCR (QRT-PCR) were used to examine the expression of CETN2 in clinical samples in relation to the effectiveness of chemotherapy. The capacity of CETN2 to predict chemotherapy results was proven by receiver operating characteristic (ROC) curves after the construction of two prediction models, the logistic regression model and the decision tree model. The impact of CETN2 on prognosis was examined using the Kaplan–Meier technique.

Results

CETN2 was associated with NER, oxidative phosphorylation (OXPHOS) and cell cycle pathways in ovarian cancer drug-resistant samples. In clinical samples, CETN2 showed its possible correlation with immune infiltration. The protein expression level of CETN2 was significantly higher in platinum-resistant patients than that in platinum-sensitive patients, and the expression level had some predictive value for chemotherapy outcome, and high CETN2 protein expression was associated with poorer progression-free survival.

Conclusions

CETN2 protein had a significant effect on ovarian cancer platinum sensitivity and prognosis, which may be related to the activation of NER, OXPHOS and cell cycle pathways upon CETN2 upregulation. Further research is necessary to determine the therapeutic application value of CETN2, which may be a new biomarker of chemoresponsiveness.

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Data availability

The data supporting the results of this study can be found in the article, or provided by the author upon reasonable requirements. Related datasets of TCGA and GEO could be downloaded from the TCGA and GEO websites.

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Funding

We are grateful for the support from grants from Guangxi Ministry of Education Key Laboratory Project [No.GKE-ZZ202020].

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Authors and Affiliations

  1. Department of Gynecologic Oncology, Guangxi Medical University Cancer Hospital, 71 He Di Road, Nanning, 530021, Guangxi, China

    Pei-yuan Qiu, Xi-han Deng & Li Li

  2. Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, 530021, Guangxi, China

    Pei-yuan Qiu, Xi-han Deng & Li Li

  3. Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, 530021, Guangxi, China

    Pei-yuan Qiu, Xi-han Deng & Li Li

Authors
  1. Pei-yuan Qiu
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Contributions

PYQ and LL designed this study. PYQ involved in bioinformatics analysis, improvement of experiments, case observation, data collection, statistical analysis, paper writing and revision. XHD observed cases, collected data, and performed the experiments. LL guided the design of clinical trials, reviewed data and statistical analysis results, and wrote and revised the paper.

Corresponding author

Correspondence to Li Li.

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The authors declare that they have no conflict of interest.

Ethical approval

All the human experiments were approved by the Ethics Committee for Guangxi Medical University Cancer Hospital and performed under protocol LW2022084.

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Informed consent was obtained from all the patients.

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Qiu, Py., Deng, Xh. & Li, L. High expression of CETN2 is associated with platinum resistance and poor prognosis in epithelial ovarian cancer. Clin Transl Oncol 25, 1340–1352 (2023). https://doi.org/10.1007/s12094-022-03031-2

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