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基因突变谱和HR-HPV感染与宫颈神经内分泌癌预后的关系研究

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目的 探讨基因突变谱和高危型人乳头瘤病毒(HR-HPV)感染对宫颈神经内分泌癌(NECC)预后不良的预测价值.方法 本回顾性研究纳入了 2016年1月至2023年8月在咸阳市第一人民医院妇科就诊且经组织学证实为NECC的79例患者.对NECC组织样本进行了分子测序,记录基因突变情况.通过流式荧光-液相芯片技术检测HR-HPV感染.研究终点为无进展生存期(PFS)和总生存期(OS).结果 PIK3CA是该队列中观察到的最常见的致癌突变(30.38%),其次是 MYC(18.99%)、TP53(16.46%)、KIT(13.92%)、RB1(10.13%)和 KRAS(3.80%).NECC 患者HR-HPV感染阳性率为37.97%.中位随访时间为24.13(2.63~67.10)个月.79例入选NECC患者的中位OS和PFS分别为42.7和38.1个月.经Cox风险分析,RB1突变和HR-HPV感染阳性可独立预测NECC患者的PFS和OS预后(P<0.05).RB1基因突变与HR-HPV感染无显著相关性(P>0.05).与RB1突变阴性患者相比,RB1突变阳性患者无进展生存率和总生存率更低,中位PFS和中位OS时间缩短(P<0.05).与HR-HPV感染阴性患者相比,HR-HPV感染阳性患者无进展生存率和总生存率更低,中位PFS和中位OS时间更短(P<0.05).根据RB1突变和HR-HPV感染联合模型,将NECC患者分为低风险(RB1突变和HR-HPV感染均阴性)、中风险(RB1突变阴性和HR-HPV感染阳性或RB1突变阳性和HR-HPV感染阴性)和高风险(RB1突变和HR-HPV感染均阳性).联合模型中,与低风险患者相比,中高风险患者的无进展生存率和总生存率更低,中位PFS时间和OS时间更短(P<0.05).结论 RB1突变和HR-HPV感染阳性与NECC患者预后不良风险增加有关,有望作为预后不良的风险预测工具.
Study on the relationship between gene mutation spectrum or HR-HPV infection and prognosis of cervical neuroendocrine carcinoma
Objective To investigate the prognostic value of gene mutation spectrum and high-risk human papillo-mavirus(HR-HPV)infection in neuroendocrine carcinoma of the uterine cervix(NECC).Methods This retrospective study included 79 patients with histologically confirmed NECC who were admitted to the gynecology department of the First Peo-ple's Hospital of Xianyang City from January 2016 to August 2023.They visited our hospital from January 2016 to August 2023.Molecular sequencing was performed on NECC tissue samples to record gene mutations.HR-HPV infection was de-tected by flow fluoro-liquid chip technique.The study endpoints were progression-free survival(PFS)and overall survival(OS).Results PIK3CA is the most common oncogenic mutation observed in this cohort(30.38%,24/79).Next are MYC(18.99%),TP53(16.46%,),KIT(13.92%),RB1(10.13%),and KRAS(3.80%).The positive rate of HR-HPV infection in NECC patients is 37.97%.The median follow-up time was 24.13(2.63 to 67.10)months.The median OS and PFS of 79 selected NECC patients were 42.7 and 38.1 months,respectively.By multiple factor Cox hazard analysis,RB1 mutation and positive HR-HPV infection can independently predict the PFS and OS prognosis of NECC patients(P<0.05).Compared with patients with negative RB1 mutations,patients with positive RB1 mutations had lower progression free survival and overall survival rates,and shorter median PFS and median OS times,with significant differences(P<0.05).Compared with patients with nega-tive HR-HPV infections,patients with positive HR-HPV infections had lower progression free survival rates and overall sur-vival rates,and shorter median PFS and median OS times,with significant differences(P<0.05).According to the combined model of RB1 mutations and HR-HPV infections,NECC patients were classified as low-risk(RB1 mutations and HR-HPV infections were both negative).Medium risk(RB1 mutation negative and HR-HPV infection positive or RB1 mutation positive and HR-HPV infection negative)and high risk(RB1 mutation positive and HR-HPV infection positive).In the joint model,compared with low-risk patients,patients with medium to high risk had lower progression free survival and overall survival rates,and shorter median PFS and OS times(P<0.05).Conclusion RB1 mutations and positive HR-HPV infection are associ-ated with an increased risk of poor prognosis in NECC,and are expected to serve as risk prediction tools for poor prognosis.

RB1 mutationHR-HPV infectionneuroendocrine carcinoma of the uterine cervixpoor prognosis

张蕾、樊雅芝、赵晓娟

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咸阳市第一人民医院妇科,陕西咸阳 712000

RB1突变 HR-HPV感染 早期宫颈神经内分泌癌 预后不良

2024

中国优生与遗传杂志
中国优生科学协会

中国优生与遗传杂志

CSTPCD
影响因子:0.527
ISSN:1006-9534
年,卷(期):2024.32(11)