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Bcl-2 and Noxa are potential prognostic indicators for patients with gastroenteropancreatic neuroendocrine neoplasms

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Abstract

Purpose

Bcl-2 family proteins are of great significance in the pathogenesis and development of tumors. In this study, the correlations between the expression of Bcl-2 family proteins and clinicopathological features and prognosis of neuroendocrine neoplasms (NENs) were further investigated.

Methods

105 Patients diagnosed with gastroenteropancreatic NENs (GEP-NENs) with the paraffin specimen of the tumor available were retrospectively included. Immunohistochemistry (IHC) was performed to detect the expression of Bcl-2 family proteins in paraffin-embedded samples. Student’s t-test and Chi-square test were applied to compare the difference of quantitative and categorical variables, respectively. Survival analysis was conducted according to Kaplan–Meier method. Univariate and multivariate cox regression analysis were used to identify the independent prognostic factors.

Results

The IHC score of Bcl-2 was significantly higher in neuroendocrine carcinoma (NEC) patients (65.6%), while a higher IHC score of Noxa was more common in neuroendocrine tumor (NET) patients (49.3%). Survival analysis indicated that patients with higher Bcl-2 expression and lower Noxa expression had worse 5-year survival (39.3% vs. 75.6%, p < 0.001; 40.6% vs. 84.9%, p < 0.001). Multivariate cox analysis indicated that high Bcl-2 expression was an independent factor associated with inferior DFS (hazard ratio [HR]: 2.092; 95% confidence interval [CI]: 1.106–3.955; p = 0.023) and OS (HR: 2.784; 95% CI: 1.326–5.846; p = 0.007), while higher Noxa expression was associated with superior DFS (HR:0.398; 95% CI: 0.175–0.907; p = 0.028) and OS (HR: 0.274; 95% CI: 0.110–0.686; p = 0.006).

Conclusions

Higher expression of Bcl-2 and lower expression of Noxa were associated with unfavorable prognosis of GEP-NENs patients.

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Author contributions

All authors contributed to the study conception and design. Data collection and analysis were performed by Y.G., L.Z., and N.Z. Experiments design: D.J.Y. and J.C. Immunohistochemical staining and analysis: M.L., Q.Y.L. Manuscript writing: Y.G., L.Z., N.Z., and L.C. All authors read and approved the final manuscript.

Funding

This work was supported by National Natural Science Foundation of China (No. 82141104); Guangzhou Science and Technology Plan (201804010078); Province Natural Science Fund of Guangdong (2019A1515011373); National Natural Science Foundation of China (82003268).

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Authors and Affiliations

  1. Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China

    Yu Guo, Ning Zhang, Luohai Chen, Man Liu & Jie Chen

  2. Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China

    Lin Zhang, Qiuyun Luo & Dajun Yang

  3. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China

    Lin Zhang, Qiuyun Luo & Dajun Yang

  4. Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China

    Lin Zhang

  5. The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518033, China

    Qiuyun Luo

  6. Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Jie Chen

  7. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    Jie Chen

  8. Department of Head & Neck tumors and Neuroendocrine Tumors, Fudan University Shanghai Cancer Center Shanghai, Shanghai, 200032, China

    Jie Chen

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  1. Yu Guo
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Correspondence to Dajun Yang or Jie Chen.

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These author contributed equally: Yu Guo, Lin Zhang and Ning Zhang.

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Guo, Y., Zhang, L., Zhang, N. et al. Bcl-2 and Noxa are potential prognostic indicators for patients with gastroenteropancreatic neuroendocrine neoplasms. Endocrine 78, 159–168 (2022). https://doi.org/10.1007/s12020-022-03114-8

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  • DOI: https://doi.org/10.1007/s12020-022-03114-8

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