术后淋巴结阴性肺浸润性黏液腺癌患者的预后预测模型

背景与目的肺浸润性黏液腺癌(invasive mucinous adenocarcinoma of the lung,IMA)是肺腺癌中一种少见且特殊的类型,该类肿瘤的特点往往是少有淋巴结转移,因此对于该类肿瘤的预后评估依靠现有的肿瘤原发灶-淋巴结-转移(tumor-node-metastasis,TNM)分期存在困难。本研究的目的是构建列线图来预测术后淋巴结阴性的IMA患者的预后。方法根据纳入标准和排除标准,回顾性分析2012年7月至2017年5月宁波大学附属李惠利医院(训练队列,n=78)和宁波市第二医院(验证队列,n=66)胸外科收治的术后病理为淋巴结阴性的IMA患者的资料,分析训练队列的临床病理特征的预后价值并建立预后预测模型,并对模型性能进行评价,最后将验证队列的数据代入进行外部验证。结果单因素分析显示肺炎型、较大的肿块、包含黏液和非黏液成分的混合型、较高的总分期是5年无进展生存期(progression-free survival,PFS)及总生存期(overall survival,OS)的影响因素。多因素分析进一步表明,影像学分型、肿块大小、黏液成分是5年PFS及OS的独立预后因素。5年PFS率和OS率分别为62.82%和75.64%,亚组的生存分析显示,肺炎型和包含黏液和非黏液成分的混合型IMA患者的5年PFS及OS分别明显低于孤立型和纯黏液型IMA患者。5年PFS和OS的Harrell’s C指数分别为0.815(95%CI:0.741-0.889)和0.767(95%CI:0.669-0.865),这两个模型的校准曲线及决策曲线分析(decision curve analysis,DCA)在两个队列中显示出良好的预测性能。结论本次基于临床病理特征构建的列线图在一定程度上可以作为IMA切除术后淋巴结阴性患者的一种有效预后预测工具。

LncRNA DPP10-AS1 promotes malignant processes through epigenetically activating its cognate gene DPP10 and predicts poor prognosis in lung cancer patients

Objective:The purpose of this study was to explore the function and gene expression regulation of the newly identified lnc RNA DPP10-AS1 in lung cancer,and its potential value as a prognostic biomarker.Methods:q RT-PCR and Western blot were conducted to detect the expression of DDP10-AS1 and DPP10 in lung cancer cell lines and tissues.The effects of DDP10-AS1 on DPP10 expression,cell growth,invasion,apoptosis,and in vivo tumor growth were investigated in lung cancer cells by Western blot,rescue experiments,colony formation,flow cytometry,and xenograft animal experiments.Results:The novel antisense lnc RNA DPP10-AS1 was found to be highly expressed in cancer tissues(P<0.0001),and its upregulation predicted poor prognosis in patients with lung cancer(P=0.0025).Notably,DPP10-AS1 promoted lung cancer cell growth,colony formation,and cell cycle progression,and repressed apoptosis in lung cancer cells by upregulating DPP10 expression.Additionally,DPP10-AS1 facilitated lung tumor growth via upregulation of DPP10 protein in a xenograft mouse model.Importantly,DPP10-AS1 positively regulated DPP10 gene expression,and both were coordinately upregulated in lung cancer tissues.Mechanically,DPP10-AS1 was found to associate with DPP10 m RNA but did not enhance DPP10 m RNA stability.Hypomethylation of DPP10-AS1 and DPP10 contributed to their coordinate upregulation in lung cancer.Conclusions:These findings indicated that the upregulation of the antisense lnc RNA DPP10-AS1 promotes lung cancer malignant processes and facilitates tumorigenesis by epigenetically regulating its cognate sense gene DPP10.DPP10-AS1 may serve as a candidate prognostic biomarker and a potential therapeutic target in lung cancer.