Identification of a Five-Gene Signature Derived From MYCN Amplification and Establishment of a Nomogram for Predicting the Prognosis of Neuroblastoma

Yuren Xia; Xin Li; Xiangdong Tian; Qiang Zhao

doi:10.3389/fmolb.2021.769661

Identification of a Five-Gene Signature Derived From MYCN Amplification and Establishment of a Nomogram for Predicting the Prognosis of Neuroblastoma

Front Mol Biosci. 2021 Dec 7:8:769661. doi: 10.3389/fmolb.2021.769661. eCollection 2021.

Authors

Yuren Xia¹, Xin Li², Xiangdong Tian¹, Qiang Zhao¹

Affiliations

¹ National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
² Tianjin Cancer Hospital Airport Hospital, Tianjin, China.

Abstract

Background: Neuroblastoma (NB), the most common solid tumor in children, exhibits vastly different genomic abnormalities and clinical behaviors. While significant progress has been made on the research of relations between clinical manifestations and genetic abnormalities, it remains a major challenge to predict the prognosis of patients to facilitate personalized treatments. Materials and Methods: Six data sets of gene expression and related clinical data were downloaded from the Gene Expression Omnibus (GEO) database, ArrayExpress database, and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. According to the presence or absence of MYCN amplification, patients were divided into two groups. Differentially expressed genes (DEGs) were identified between the two groups. Enrichment analyses of these DEGs were performed to dig further into the molecular mechanism of NB. Stepwise Cox regression analyses were used to establish a five-gene prognostic signature whose predictive performance was further evaluated by external validation. Multivariate Cox regression analyses were used to explore independent prognostic factors for NB. The relevance of immunity was evaluated by using algorithms, and a nomogram was constructed. Results: A five-gene signature comprising CPLX3, GDPD5, SPAG6, NXPH1, and AHI1 was established. The five-gene signature had good performance in predicting survival and was demonstrated to be superior to International Neuroblastoma Staging System (INSS) staging and the MYCN amplification status. Finally, a nomogram based on the five-gene signature was established, and its clinical efficacy was demonstrated. Conclusion: Collectively, our study developed a novel five-gene signature and successfully built a prognostic nomogram that accurately predicted survival in NB. The findings presented here could help to stratify patients into subgroups and determine the optimal individualized therapy.

Keywords: MYCN amplification; gene signature; neuroblastoma; nomogram; prognosis.