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神秘的解旋酶DHX9作为切除性胰腺导管腺癌的候选预后生物标志物。

The enigmatic helicase DHX9 as a candidate prognostic biomarker for resected pancreatic ductal adenocarcinoma.

作者信息

Chen Le-Gao, Cui Ying, Lu Wei-Qin, Wu Hao, Jiang Jin-Song, Ding Ke-Feng

机构信息

Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China.

出版信息

Front Oncol. 2022 Dec 12;12:1066717. doi: 10.3389/fonc.2022.1066717. eCollection 2022.

Abstract

BACKGROUND

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, and current therapies have limited efficacy on PDAC. The DEAH-box helicase 9 (DHX9) is widely reported to influence cell biological behavior regulating DNA replication, genomic stability, transcription, translation, and microRNA biogenesis. However, the prognostic role of DHX9 in PDAC remains unclear. Thus, the objective of this study is to investigate the prognostic value of DHX9 expression in PDAC patients.

METHODS

Tumor specimens from PDAC patients with surgical resection were obtained, and DHX9 was stained and analyzed in this study. Univariate and multivariate Cox regression analyses were utilized to identify independent risk factors of overall survival (OS) and recurrence-free survival (RFS). The prognostic nomograms for predicting OS and RFS were established to obtain superior predictive power.

RESULTS

Among the enrolled 110 patients, 61 patients were identified as having high expression of DHX9. The correlation analysis revealed that higher DHX9 expression in PDAC was prone to have advanced N stage ( = 0.010) and TNM stage ( = 0.017). For survival, the median OS (21.0 vs. 42.0 months, < 0.001) and RFS (12.0 vs. 24.0 months, < 0.001) of patients in the high DHX9 group were significantly shorter than those in the low DHX9 group. Within the univariate and multivariate analyses, American Joint Committee on Cancer (AJCC) N stage ( = 0.036) and DHX9 expression ( = 0.041) were confirmed as independent prognostic factors of OS, while nerve invasion ( = 0.031) and DHX9 expression ( = 0.005) were independent prognostic factors of RFS. Finally, the novel prognostic nomograms for OS and RFS were established and showed superior predictive accuracy.

CONCLUSION

This study identified the independent prognostic value of DHX9 for RFS and OS in resected PDAC patients, and higher DHX9 expression was prone to have an earlier recurrence and shorter OS. Therefore, DHX9 may be a promising and valuable biomarker and a potential target for treating PDAC. More accurate and promising predictive models would be achieved when DHX9 is incorporated into nomograms.

摘要

背景

胰腺导管腺癌(PDAC)仍然是最致命的恶性肿瘤之一,目前的治疗方法对PDAC的疗效有限。DEAH框解旋酶9(DHX9)被广泛报道可影响细胞生物学行为,调节DNA复制、基因组稳定性、转录、翻译和微小RNA生物合成。然而,DHX9在PDAC中的预后作用仍不清楚。因此,本研究的目的是探讨DHX9表达在PDAC患者中的预后价值。

方法

获取接受手术切除的PDAC患者的肿瘤标本,本研究对DHX9进行染色和分析。采用单因素和多因素Cox回归分析来确定总生存期(OS)和无复发生存期(RFS)的独立危险因素。建立预测OS和RFS的预后列线图以获得更好的预测能力。

结果

在纳入的110例患者中,61例患者被确定为DHX9高表达。相关性分析显示,PDAC中较高的DHX9表达倾向于具有晚期N分期(P = 0.010)和TNM分期(P = 0.017)。在生存方面,高DHX9组患者的中位OS(21.0对42.0个月,P < 0.001)和RFS(12.0对24.0个月,P < 0.001)明显短于低DHX9组。在单因素和多因素分析中,美国癌症联合委员会(AJCC)N分期(P = 0.036)和DHX9表达(P = 0.041)被确认为OS的独立预后因素,而神经侵犯(P = 0.031)和DHX9表达(P = 0.005)是RFS的独立预后因素。最后,建立了新的OS和RFS预后列线图,显示出卓越的预测准确性。

结论

本研究确定了DHX9对接受手术切除的PDAC患者的RFS和OS具有独立预后价值,且较高的DHX9表达倾向于更早复发和更短的OS。因此,DHX9可能是一个有前景且有价值的生物标志物以及治疗PDAC的潜在靶点。当将DHX9纳入列线图时,将实现更准确和有前景的预测模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3de3/9791203/efe65be05076/fonc-12-1066717-g001.jpg

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