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DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation

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Cancer Biology & Medicine 2024年第3期21卷 252-266页

作者： Junya Yan Shibo Wang Jing Zhang Qiangqiang Yuan Xianchun Gao Nannan Zhang Yan Pan Haohao Zhang Kun Liu Jun Yu Linbin Lu Hui Liu Xiaoliang Gao Sheng Zhao Wenyao Zhang Abudurousuli Reyila Yu Qi Qiujin Zhang shundong cang Yuanyuan Lu Yanglin Pan Yan Kong Yongzhan Nie State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases Xijing Hospital of Air Force Military Medical UniversityXi'an 710032China Department of Oncology Henan Provincial People's HospitalZhengzhou University People's HospitalZhengzhou 450o03China Faculty of Life Science Northwest UniversityXi'an 710069China Unit 73211 of the People's Liberation Army Nanjing 211800China Key Laboratory of Resource Biology and Biotechnology in Western China(Ministry of Education) School of MedicineNorthwest UniversityXi'an 710069China Shaanxi University of Chinese Medicine Second Clinical Medicine FacultyXi'an 712046China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of Renal Cancer and MelanomaPeking University Cancer Hospital and InstituteBeijing 100142China

Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) ***: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published ***: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and ***: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

关键词： DNA damage response-related immune activation immune checkpoint inhibitors biomarker gastrointestinal cancer pan-cancer

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MYH9在消化道肿瘤中的研究进展

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胃肠病学和肝病学杂志 2024年第1期33卷 78-82页

作者：宋猛徐登飞仓顺东郑州大学人民医院肿瘤中心河南郑州450000

消化道肿瘤是我国常见的恶性肿瘤,发病率逐年上升。长期以来,消化道肿瘤的发病率和病死率未表现出明显下降的态势,寻找并确定有效的诊断和治疗靶点刻不容缓。MYH9又称肌球蛋白ⅡA或非肌肉肌球蛋白重链9,是Ⅱ类常规肌球蛋白的一个226 kD... 详细信息

消化道肿瘤是我国常见的恶性肿瘤,发病率逐年上升。长期以来,消化道肿瘤的发病率和病死率未表现出明显下降的态势,寻找并确定有效的诊断和治疗靶点刻不容缓。MYH9又称肌球蛋白ⅡA或非肌肉肌球蛋白重链9,是Ⅱ类常规肌球蛋白的一个226 kDa的亚基,以六聚酶的形式存在,由两条重链和两对轻链组成,MYH9与细胞质中的肌动蛋白相互作用,参与不同的细胞过程,如细胞运动、细胞迁移和细胞粘附。近来有研究发现,MYH9在食管鳞状细胞癌、胃癌、结直肠癌等恶性肿瘤中高度表达并促进其侵袭进展。然而,MYH9在消化道肿瘤中的具体发生机制尚不明确,本文对近年相关研究进行综述,旨在探讨MYH9在消化道肿瘤中未来的研究及临床价值。

关键词：消化道肿瘤 MYH9 lncRNA miRNA circRNAs

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Updated overall survival and circulating tumor DNA analysis of ensartinib for crizotinib-refractory ALK-positive NSCLC from a phase II study

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Cancer Communications 2024年第4期44卷 455-468页

作者： Jing Zheng Tao Wang Yunpeng Yang Jie Huang Jifeng Feng Wu Zhuang Jianhua Chen Jun Zhao Wei Zhong Yanqiu Zhao Yiping Zhang Yong Song Yi Hu Zhuang Yu Youling Gong Yuan Chen Feng Ye Shucai Zhang Lejie Cao Yun Fan Gang Wu Yubiao Guo Chengzhi Zhou Kewei Ma Jian Fang Weineng Feng Yunpeng Liu Zhendong Zheng Gaofeng Li Huijie Wang shundong cang Ning Wu Wei Song Xiaoqing Liu Shijun Zhao Lieming Ding Giovanni Selvaggi Yang Wang Shanshan Xiao Qian Wang Zhilin Shen Jianya Zhou Jianying Zhou Li Zhang Department of Respiratory Disease Thoracic Disease CenterThe First Affiliated HospitalCollege of MedicineZhejiang UniversityZhejiang Provincial Clinical Research Center for Respiratory DiseaseHangzhouZhejiangP.R.China Hangzhou Repugene Technology Co. LtdHangzhouZhejiangP.R.China Department of Medical Oncology Sun Yat-sen University Cancer Cen-terState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdongP.R.China Department of Medical Oncology Jiangsu Cancer HospitalJiangsu Institute of Cancer ResearchThe Affiliated Cancer Hospital of Nanjing Medical UniversityNanjingJiangsuP.R.China Department of Thoracic Oncology Fujian Provincial Cancer HospitalFujian Medical University Cancer HospitalFuzhouFujianP.R.China Department of Medical Oncology-Chest Hunan Cancer HospitalChangshaHunanP.R.China Department of Thoracic Oncology Beijing Cancer HospitalBeijingP.R.China Department of Pulmonary Medicine Peking Union Medical College HospitalChinese Academy of Medical SciencesPeking Union Medical CollegeBeijingP.R.China Respiratory Department of Internal Medicine Henan Provincial Can-cer HospitalAffiliated Cancer Hospital of Zhengzhou UniversityZhengzhouHenanP.R.China Thoracic Medical Oncology Zhejiang Cancer HospitalHangzhouZhejiangP.R.China Division of Respiratory Medicine Jinling HospitalNanjing University School of MedicineNanjingJiangsuP.R.China Department of Oncology Chinese People’s Liberation Army(PLA)General HospitalBeijingP.R.China Department of Oncology The Affiliated Hospital of Qingdao UniversityQingdaoShandongP.R.China Department of Thoracic Oncology Cancer CenterWest China HospitalSichuan UniversityChengduSichuanP.R.China Department of Oncology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China Department of Medical Oncology Cancer HospitalThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityTeaching Hospital of

Background:The initial phase II stuty(NCT03215693)demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib-refractory,anaplastic lymphoma kinase(ALK)-positive non-small cell lung cancer(NSCLC).Herein,we reported the updated data on overall survival(OS)and molecular profiling from the initial phase Ⅱ ***:In this study,180 patients received 225 mg of ensartinib orally once daily until disease progression,death or *** was estimated by Kaplan‒Meier methods with two-sided 95%confidence intervals(CIs).Next-generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating *** tumor DNA(ctDNA)was detected to dynamically monitor the genomic alterna-tions during treatment and indicate the existence of molecular residual disease,facilitating improvement of clinical ***:At the data cut-off date(August 31,2022),with a median follow-up time of 53.2 months,97 of 180(53.9%)patients had *** median OS was 42.8 months(95%CI:29.3-53.2 months).A total of 333 plasma samples from 168 patients were included for ctDNA *** inferior OS correlated sig-nificantly with baseline ALK or tumor protein 53(TP53)*** addition,patients with concurrent TP53 mutations had shorter OS than those without con-current TP53 *** ctDNA levels evaluated by variant allele frequency(VAF)and haploid genome equivalents per milliliter of plasma(hGE/mL)at baseline were associated with poor ***,patients with ctDNA clear-ance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth,***,patients who had a lower tumor burden,as evaluated by the diameter of target lesions,had a longer *** Cox regression analysis further uncovered the independent prognostic values of bone metastases,higher hGE,and elevated ALK mutation abundance at 6 we

关键词： anaplastic lymphoma kinase ctDNA ensartinib non-small cell lung cancer overall survival

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肠道微生物与免疫检查点阻断剂相互作用机制的研究进展

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临床肿瘤学杂志 2020年第4期25卷 374-377页

作者：陈星星仓顺东郑州大学人民医院肿瘤内科郑州450003

随着免疫治疗2.0时代的到来,免疫检查点阻断剂(ICIs)已成为多种类型肿瘤治疗的新选择。多项研究表明,肿瘤患者肠道微生物与ICIs治疗反应密切相关,肠道微生物通过易位、免疫调节、代谢、酶促降解和多样性变异影响ICIs的疗效。此外,ICIs... 详细信息

随着免疫治疗2.0时代的到来,免疫检查点阻断剂(ICIs)已成为多种类型肿瘤治疗的新选择。多项研究表明,肿瘤患者肠道微生物与ICIs治疗反应密切相关,肠道微生物通过易位、免疫调节、代谢、酶促降解和多样性变异影响ICIs的疗效。此外,ICIs在改变肠道微生物组成和减少细菌多样性的同时,增加了胃肠道免疫相关不良反应。肠道微生物在预测ICIs疗效及免疫毒性方面有其独特的临床价值,故对应用ICIs的肿瘤患者进行肠道微生物分析已成为一种潜在需求。本综述主要介绍肠道微生物与ICIs相互作用机制的最新研究进展,以便更好地识别ICIs的应答者并提高其疗效和安全性。

关键词：肿瘤肠道微生物免疫检查点阻断剂(ICIs) 相互作用

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LINC01559/MYH9 axis promotes the growth of gastric cancer via Wnt/β-catenin signaling pathway

LINC01559/MYH9 axis promotes the growth of gastric cancer vi...

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2021年中国肿瘤标志物学术大会暨第十五届肿瘤标志物青年科学家论坛

作者： Yuming Chen Hao Feng Haofeng Zhang Zirui Ren Xiang Li Chenyang Jiang Dengfei Xu shundong cang Zhengzhou University People's Hospital 河南省人民医院河南大学人民医院

Research purposes: Gastric cancer(GC) is one of the most common malignant tumors of the digestive system. The etiology of GC is complex, and much more attention should be paid to genetic *** present study aimed to determine the potential functions and the molecular mechanisms of long intergenic non-protein coding RNA 1559(LINC01559) underlying progression of gastric cancer(GC).Materials and methods: A quantitative reverse transcriptase-polymerase chain reaction(qRT-PCR) was used to measure the expression of LINC01559 in GC cell lines and normal cells. After silencing LINC01559 in GC cells, a cell counting kit-8 assay monitored the viability of the cells. qRT-PCR and western blot documented the EMT key genes in response to LINC01559 change. In order to explore the role of LINC01559 in vivo, we subcutaneous inoculated or injected through the tail vein with AGS cells stably knocking down LINC01559 or control cells to establish xenograft tumor growth model or lung metastasis model. Mechanistically, chromatin immunoprecipitation, luciferase reporter, RNA pulldown, mass spectrum, RNA immunoprecipitation and fluorescence in situ hybridization assays were ***: LINC01559 was significantly upregulated in GC tissues from GEPIA database(Figure 1) and cells(Figure 2). Knockdown of LINC01559 strikingly inhibited the proliferation and invasion of GC cells in vitro(Figure 3-5). Further mechanistic research proved that LINC01559 can bind to myosin heavy chain 9(MYH9)by RNA pull-down assay and mass spectrometry analysis(Figure 6). RNA immunoprecipitation(RIP) experiments confirm the binding of LINC01559 to MYH9(Figure 7).Knocking down of LINC01559 could inhibit the expression of MYH9, and also influence the protein expression of β-catenin and p-GSK3β(Figure 8), which are key molecules of the Wnt/β-catenin signaling pathway. It suggested that abnormal expression of LINC01559 could influence aberrantly activation of the Wnt/β-catenin signaling pathway and promoted

关键词： LINC01559 gastric cancer MYH9 β-catenin

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骨髓间充质干细胞移植治疗糖尿病及其并发症的现状及研究进展

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中国糖尿病杂志 2018年第2期26卷 166-169页

作者：李冉冉陈亚斌仓顺东郑州大学人民医院肿瘤内科 450003 郑州大学第一附属医院肝胆外科

骨髓间充质干细胞(BMSCs)具有很强的自我更新能力和多向分化潜能,是细胞移植的理想细胞,在临床上广泛用于治疗糖尿病、骨关节病等。BMSCs通过增加患者体内胰岛素和C-P水平,使患者不依赖外源性胰岛素即可良好地控制血糖。近年来,多项研... 详细信息

骨髓间充质干细胞(BMSCs)具有很强的自我更新能力和多向分化潜能,是细胞移植的理想细胞,在临床上广泛用于治疗糖尿病、骨关节病等。BMSCs通过增加患者体内胰岛素和C-P水平,使患者不依赖外源性胰岛素即可良好地控制血糖。近年来,多项研究证实了BMSCs移植治疗糖尿病的安全性及有效性。BMSCs移植治疗糖尿病肾脏疾病(DKD)、糖尿病周围血管病、糖尿病心肌病、糖尿病骨病等并发症也取得了良好的效果。然而,由于缺乏标准化的移植方案,BMSCs移植在临床上应用受到了限制。本文通过回顾文献,总结了BMSCs移植在治疗糖尿病及其并发症的现状和研究进展。

关键词：骨髓间充质干细胞糖尿病糖尿病并发症

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吉西他滨联合顺铂方案与多西他赛联合顺铂方案治疗非小细胞肺癌的疗效比较

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中国实用医刊 2019年第8期46卷 79-82页

作者：杨琳仓顺东郑州大学人民医院郑州450000

目的比较吉西他滨联合顺铂方案与多西他赛联合顺铂方案治疗非小细胞肺癌(NSCLC)的临床疗效。方法选取2015年6月至2017年8月郑州大学人民医院收治的NSCLC患者68例,根据治疗方案不同分为DP组与GP组,每组34例。DP组采用多西他赛联合顺铂化... 详细信息

目的比较吉西他滨联合顺铂方案与多西他赛联合顺铂方案治疗非小细胞肺癌(NSCLC)的临床疗效。方法选取2015年6月至2017年8月郑州大学人民医院收治的NSCLC患者68例,根据治疗方案不同分为DP组与GP组,每组34例。DP组采用多西他赛联合顺铂化疗方案治疗,GP组采用吉西他滨联合顺铂化疗方案治疗。比较两组化疗效果、化疗期间不良反应发生情况,并比较两组化疗前、化疗2个周期后凝血状态[凝血酶原时间(PT)、凝血酶时间(TT)、纤维蛋白原(FIB)]变化情况。结果化疗2个周期后,GP组疾病控制率[79.41%(27/34)]与DP组[76.47%(26/34)]比较,差异未见统计学意义(P>0.05);GP组化疗期间肌肉酸痛、脱发发生率低于DP组,贫血、血小板计数减少、恶心呕吐发生率高于DP组,差异有统计学意义(P0.05);化疗2个周期后,GP组TT长于DP组,FIB低于DP组,差异有统计学意义(P<0.05)。结论吉西他滨联合顺铂方案与多西他赛联合顺铂治疗NSCLC的疗效相近,吉西他滨联合顺铂方案不良反应主要表现为贫血、血小板计数减少、恶心呕吐,多西他赛联合顺铂方案不良反应主要表现为肌肉酸痛、脱发,临床治疗时需采用不同辅助治疗方法;与多西他赛联合顺铂方案化疗比较,吉西他滨联合顺铂方案能延长凝血酶时间,改善患者体内纤溶功能,更有利于改善患者预后。

关键词：非小细胞肺癌多西他赛吉西他滨顺铂化疗不良反应临床疗效

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LINC01559在恶性肿瘤中的研究进展

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河南医学研究 2023年第10期32卷 1907-1912页

作者：李祥郭燕仓顺东河南大学人民医院/河南省人民医院肿瘤中心河南郑州450003

长链非编码RNA(lncRNA)是一种新型的非蛋白编码RNA,长度大于200个核苷酸。长链非编码核糖核酸1599(LINC01559)是一种新发现的lncRNA,近年研究发现,LINC01559在消化、呼吸、乳腺、泌尿等多系统的恶性肿瘤中表达升高,并与癌症患者预后不... 详细信息

长链非编码RNA(lncRNA)是一种新型的非蛋白编码RNA,长度大于200个核苷酸。长链非编码核糖核酸1599(LINC01559)是一种新发现的lncRNA,近年研究发现,LINC01559在消化、呼吸、乳腺、泌尿等多系统的恶性肿瘤中表达升高,并与癌症患者预后不良呈正相关。此外,LINC01559参与恶性肿瘤细胞的增殖、侵袭、转移及耐药多个过程中。随着深入研究证实,LINC01559调控癌症发生发展的机制主要是作为竞争性内源RNA,调节microRNA(miRNA)及其下游靶基因的表达。本文结合国内外最新报道,就LINC01559在各恶性肿瘤中的作用及其潜在作用机制的研究进行综述。

关键词：长链非编码核糖核酸1599 长链非编码RNA 内源性竞争RNA 恶性肿瘤

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Efficacy,safety and pharmacokinetics of Unecritinib(TQ-B3101)for patients with ROS1 positive advanced non-small cell lung cancer:a Phase I/II Trial

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Signal Transduction and Targeted Therapy 2023年第7期8卷 3536-3546页

作者： Shun Lu Hongming Pan Lin Wu Yu Yao Jianxing He Yan Wang Xiuwen Wang Yong Fang Zhen Zhou Xicheng Wang Xiuyu Cai Yan Yu Zhiyong Ma Xuhong Min Zhixiong Yang Lejie Cao Huaping Yang Yongqian Shu Wu Zhuang shundong cang Jian Fang Kai Li Zhuang Yu Jiuwei Cui Yang Zhang Man Li Xinxuan Wen Jie Zhang Weidong Li Jianhua Shi Xingxiang Xu Diansheng Zhong Tao Wang Jiajia Zhu Department of Medical Oncology Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong University200030 ShanghaiChina Department of Medical Oncology Sir Run Run Shaw HospitalZhejiang University310016 HangzhouChina Department of Thoracic Medical Oncology The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South University(Hunan Cancer Hospital)410031 ChangshaChina Department of Medical Oncology The First Affiliated Hospital of Xi’an Jiaotong University710061 XianChina Department of Thoracic Surgery The First Affiliated Hospital of Guangzhou Medical University510120 GuangzhouChina Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College100021 BeijingChina Department of Oncology Qilu Hospital of Shandong University250012 JinanChina Department of Oncology The First Affiliated Hospital/School of Clinical Medicine of Guangdong Pharmaceutical University510699 GuangzhouChina Department of Medical Oncology Sun Yat-sen University Cancer Center510060 GuangzhouChina Department of Respiratory Medicine Harbin Medical University Cancer Hospital150081 HarbinChina Department of Medical Oncology Henan Tumor Hospital450003 ZhengzhouChina Department of Oncology Radiotherapy Anhui Chest Hospital230022 HefeiChina Department of Cancer Center Affiliated Hospital of Guangdong Medical University524000 ZhanjiangChina Department of Respiratory Medicine The First Affiliated Hospital of the University of Science and Technology of ChinaAnhui Provincial Hospital230031 HefeiChina Department of Respiratory and Critical Care Medicine Xiangya Hospital Central South University410008 ChangshaChina Department of Cancer Center Jiangsu Province Hospital210029 NanjingChina Department of Thoracic Oncology Fujian Cancer Hospital and Fujian Medical University Cancer Hospital350014 FuzhouChina Department of Medical Oncology Henan Province People’s Hospital450003 ZhengzhouCh

This phase I/II trial characterized the tolerability,safety,and antitumor activities of unecritinib,a novel derivative of crizotinib and a multi-tyrosine kinase inhibitor targeting ROS1,ALK,and c-MET,in advanced tumors and ROS1 inhibitor-naive advanced or metastatic non-small cell lung cancer(NSCLC)harboring ROS1 *** patients received unecritinib 100,200.

关键词： patients lung cancer

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体质量变化对老年晚期胃癌患者化疗效果的影响

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中国实用医刊 2019年第1期46卷 36-40页

作者：周凤杰仓顺东河南省人民医院郑州450003

目的探讨体质量变化对老年晚期胃癌患者化疗效果的影响。方法选取2012年1月至2017年6月河南省人民医院收治的老年晚期胃癌患者100例,根据患者个体情况给予奥沙利铂联合替吉奥方案(SOX方案)与奥沙利铂联合氟尿嘧啶、亚叶酸钙方案(mFOLFOX... 详细信息

目的探讨体质量变化对老年晚期胃癌患者化疗效果的影响。方法选取2012年1月至2017年6月河南省人民医院收治的老年晚期胃癌患者100例,根据患者个体情况给予奥沙利铂联合替吉奥方案(SOX方案)与奥沙利铂联合氟尿嘧啶、亚叶酸钙方案(mFOLFOX4方案)进行化疗。根据化疗过程中患者体质量的增减进行分组,其中体质量增加的48例患者作为观察组,体质量减轻的52例患者作为对照组。化疗后2个周期,比较两组患者的化疗效果及不良反应。结果化疗后,两组客观缓解率比较差异未见统计学意义(P0.05)。两组不良反应主要以骨髓抑制、胃肠道反应和神经毒性等为主,对照组贫血发生率高于观察组(P0.05)。结论化疗过程中,患者体质量增加时,贫血发生率下降,可增强患者免疫力,延长无进展生存期。

关键词：老年患者晚期胃癌化疗体质量变化

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