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Frontiers of Medicine 2024年第3期18卷 565-569页

作者： Jia Jia Lili Mao Jing Lin Wenyu Li Pei Yuan Lei Guo Jie Dai Caili Li Xue Bai Zhongwu Li Yu Chen Jun Guo jianming ying Lu Si State Key Laboratory of Molecular Oncology Department of PathologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100021China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Melanoma and SarcomaPeking University Cancer Hospital&InstituteBeijing100142China Department of Medical Oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou350014China Department of Pathology Peking University Cancer Hospital&InstituteBeijing100142China

Dear Editor,Extramammary Paget disease(EMPD)is a rare adenocarcinoma that originates in the apocrine gland-rich skin and usually affects the perineal skin(primary EMPD)or represents the intraepithelial spread of an underlying visceral carcinoma(secondary EMPD).Approximately half of EMPD cases are confined to the epidermis,which was defined as intraepithelial EMPD.

关键词： Paget HER2 adenocarcinoma

Erratum to:Potential unreliability of ALK variant allele frequency in the efficacy prediction of targeted therapy in NSCLC

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Frontiers of Medicine 2024年第3期18卷 570-570页

作者： Wei Rao Yutao Liu Yan Li Lei Guo Tian Qiu Lin Dong jianming ying Weihua Li Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100021China Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100021China

The original version of this article unfortunately contained a *** original Fig.1A(Page 495),the frequency of ALK fusions detected by FISH was erroneously stated as“326/4670”,and the correct value should be“359/4670”.The other elements of the figure remain the same,and the interpretation of the results remains *** authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.

关键词： NSCLC stated unchanged

KRAS G12C突变在消化系统恶性肿瘤中的分子特点

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肝癌电子杂志 2024年第1期11卷 4-8页

作者：赵挺祺董林应建明李卫华巴彦淖尔市医院病理科内蒙古巴彦淖尔市015000 国家癌症中心/国家肿瘤临床研究中心/中国医学科学院北京协和医学院肿瘤医院病理科北京100021

目的:探究KRAS G12C突变在不同消化系统恶性肿瘤中的发生率及分子病理特点。方法:收集2017—2022年在中国医学科学院肿瘤医院诊断为消化系统恶性肿瘤且有肿瘤组织样本的1100例患者资料。使用二代测序的方法对1100例消化系统恶性肿瘤组... 详细信息

目的:探究KRAS G12C突变在不同消化系统恶性肿瘤中的发生率及分子病理特点。方法:收集2017—2022年在中国医学科学院肿瘤医院诊断为消化系统恶性肿瘤且有肿瘤组织样本的1100例患者资料。使用二代测序的方法对1100例消化系统恶性肿瘤组织样本(包括结肠腺癌、直肠腺癌、回盲肠腺癌、十二指肠腺癌、胃腺癌、胆管腺癌和胰腺导管腺癌)的微卫星状态和肿瘤突变负荷(TMB),以及KRAS、NRAS、BRAF、PIK3CA突变进行检测。结果:微卫星高度不稳定(MSI-H)在不同消化系统肿瘤中存在差异,其中在十二指肠腺癌发生率最高(19%),其次为回盲肠腺癌(18%)和结肠腺癌(10.2%),但在100例胰腺导管腺癌中未检出MSI-H的肿瘤。不同消化系统恶性肿瘤的TMB值亦有差异,高TMB(≥10 mut/Mb)在回盲肠腺癌中最常见(24%),其次为十二指肠腺癌(22%)和胃腺癌(18.9%)。KRAS在总人群中的突变率为41.09%,其中在胰腺导管腺癌中突变率最高(85.0%),其次为十二指肠腺癌(56%)和回盲肠腺癌(53%),在胃腺癌中最低(7.3%)。KRAS G12C在总人群中的突变率为2.82%(31/1100),在所有KRAS突变的消化系统肿瘤中仅占6.9%(31/452),常见于回盲肠腺癌(2/9),其次为十二指肠腺癌(13%)和结肠腺癌(8.8%)。KRAS G12C突变和其他KRAS突变亚型患者的性别、年龄、MSI和TMB状态相近。结论:虽然近一半的消化系统恶性肿瘤患者携带有KRAS突变,但KRAS G12C突变发生率相对较低,只占KRAS突变人群的6.9%。KRAS G12C突变最常见于回盲肠腺癌、十二指肠腺癌和结肠腺癌,且与其他类型的KRAS突变相比未见明显的临床和分子病理特征差异。

关键词：消化系统肿瘤二代测序 KRAS G12C突变

Clinical characteristics and response to tyrosine kinase inhibitors of patients with non-small cell lung cancer harboring uncommon epidermal growth factor receptor mutations

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Chinese Journal of Cancer Research 2017年第1期29卷 18-24页

作者： Yan Zhang Zheng Wang Xuezhi Hao Xingsheng Hu Hongyu Wang Yan Wang jianming ying Department of Medical Oncology National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100021 China Department of Pathology Beijing Hospital National Center of Gerontology Beijing 100730 China Departmentof Pathology National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100021China

Objective： To investigate the clinical features of patients with non-small cell lung cancer（NSCLC） harboring uncommon epidermal growth factor receptor（EGFR） mutations, and the treatment outcomes of EGFR tyrosine kinase inhibitors（TKIs） in these ***： We retrospectively analyzed the data of 128 NSCLC patients pathologically diagnosed with uncommon EGFR mutation in the Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences ＆ Peking Union Medical College and Beijing Hospital from January 2010 to December 2015, including 40 advanced patients who received ***： Among the total 128 patients, 11 patients were non-adenocarcinoma, including squamous carcinoma（3.9%）, adenosquamous carcinoma（2.3%）, large cell carcinoma（0.8%）, and composite neuroendocrine carcinoma（1.6%）. Single mutations accounted for 75.0%（96/128）, including G719X（29.7%）, S768I（18.0%）, 20 exon insertion（13.3%）, L861Q（12.5%）, De novo T790M（0.8%）, and T725（0.8%）. Thirty-two patients harbored complex mutations. Forty advanced patients received EGFR-TKI, the objective response rate（ORR） was 20.0%,the disease control rate（DCR） was 85.0%, and the progression-free survival（PFS） was 6.4 [95% confidence interval（95% CI）, 4.8–7.9] months. The exploratory analysis of tumor response and PFS in 33 patients with G719X/S768I/L861 Q subtypes showed that ORR was 21.2%（7/33）, the DCR was 93.9%（31/33）, and PFS was 7.6（95% CI, 5.8–9.4） months. Patients with exon 20 insertion mutation and De novo T790 M experienced rapid disease progression with PFS no more than 2.7 ***： Uncommon EGFR-mutant NSCLCs are heterogeneous, EGFR-TKIs can have different efficacy in this specific subtype, and thus further individual assessment is required for each case.

关键词： Non-small cell lung cancer EGFR uncommon mutation target therapy

Potential unreliability of ALK variant allele frequency in the efficacy prediction of targeted therapy in NSCLC

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Frontiers of Medicine 2023年第3期17卷 493-502页

作者： Wei Rao Yutao Liu Yan Li Lei Guo Tian Qiu Lin Dong jianming ying Weihua Li Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Anaplastic lymphoma kinase(ALK)is the most common fusion gene involved in non-small cell lung cancer(NSCLC),and remarkable response has been achieved with the use of ALK tyrosine kinase inhibitors(ALK-TKIs).However,the clinical efficacy is highly ***-existing intratumoral heterogeneity(ITH)has been proven to contribute to the poor treatment response and the resistance to targeted *** this work,we investigated whether the variant allele frequencies(VAFs)of ALK fusions can help assess ITH and predict targeted therapy *** the application of next-generation sequencing(NGS),7.2%(326/4548)of patients were detected to be ALK *** the basis of the adjusted VAF(adjVAF,VAF normalization for tumor purity)of four different threshold values(adjVAF<50%,40%,30%,or 20%),the association of ALK subclonality with crizotinib efficacy was ***,no statistical association was observed between median progression-free survival(PFS)and ALK subclonality assessed by adjVAF,and a poor correlation of adjVAF with PFS was found among the 85 patients who received first-line *** suggest that the ALK VAF determined by hybrid capture-based NGS is probably unreliable for ITH assessment and targeted therapy efficacy prediction in NSCLC.

关键词： ALK fusion next-generation sequencing fluorescence in situ hybridization immunohistochemistry variant allele frequency intratumoral heterogeneity targeted therapy

Comprehensive analysis of the prognostic impact and immune implication of KIAA1429 in lung adenocarcinoma

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Cancer Innovation 2022年第4期1卷 328-343页

作者： Lei Guo Qilin Huai Bolun Zhou jianming ying Wei Guo Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingThe People's Republic of China Department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingThe People's Republic of China Key Laboratory of Minimally Invasive Therapy Research for Lung Cancer Chinese Academy of Medical SciencesBeijingThe People's Republic of China

Background:Lung adenocarcinoma(LUAD)is the most common lung cancer worldwide.N6-methyladenosine(m6A)methylation is a messenger RNA(mRNA)modification that plays a key role in tumor growth,immune microenvironment,and immunotherapy *** study investigated the expression level,mutation status,prognostic value,and predictive ability for response to anti-PD-1 immunotherapy of the m6A methyltransferase KIAA1429 in ***:This study examined multiple public data cohorts and independent samples from National Cancer Center(NCC)to evaluate the clinical significance and prognostic value of KIAA1429 in LUAD using bioinformatics techniques and immunohistochemical *** also evaluated the predictive value of KIAA1429 expression for anti-PD-1 immunotherapy *** analysis was performed using KIAA1429 RNA-seq data at the tumor tissue level and cellular level to explore the potential molecular ***:In public databases,KIAA1429 was significantly associated with clinicopathological parameters in LUAD patients and had the potential to predict patient *** mutation characteristics of KIAA1429-related genes were analyzed and TP53,TTN,CSMD3,and other genes showed high mutation frequencies in *** independent cohort of 415 samples confirmed that high KIAA1429 expression was significantly associated with poorer prognosis in LUAD *** of a small immunotherapy cohort showed that patients with high expression of KIAA1429 had better response after immunotherapy,and the proportion of patients with immunotherapy response was higher in this ***:Our study confirmed that KIAA1429 was highly expressed in LUAD and was significantly associated with poor ***,KIAA1429 may serve as a potential marker to predict the efficacy of immunotherapy in LUAD.

关键词： KIAA1429 lung adenocarcinoma m6A methylation immunotherapy prognosis

Patient Assessment and Therapy Planning Based on Homologous Recombination Repair Deficiency

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Genomics, Proteomics & Bioinformatics 2023年第5期21卷 962-975页

作者： Wenbin Li Lin Gao Xin Yi Shuangfeng Shi Jie Huang Leming Shi Xiaoyan Zhou Lingying Wu jianming ying Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Geneplus–Shenzhen Shenzhen 518000China Institute of Microbiology Chinese Academy of SciencesBeijing 100101China Geneplus–Beijing Beijing 102206China National Institutes for Food and Drug Control Beijing 100050China State Key Laboratory of Genetic Engineering Human Phenome InstituteSchool of Life SciencesFudan UniversityShanghai 200438China Department of Pathology Fudan University Shanghai Cancer CenterShanghai 200032China Department of Gynecologic Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Defects in genes involved in the DNA damage response cause homologous recombination repair deficiency(HRD).HRD is found in a subgroup of cancer patients for several tumor types,and it has a clinical relevance to cancer prevention and *** evidence has identified HRD as a biomarker for assessing the therapeutic response of tumor cells to poly(ADP-ribose)polymerase inhibitors and platinum-based ***,the biology of HRD is complex,and its applications and the benefits of different HRD biomarker assays are *** is primarily due to inconsistencies in HRD assessments and definitions(gene-level tests,genomic scars,mutational signatures,or a combination of these methods)and difficulties in assessing the contribution of each genomic ***,we aim to review the biological rationale and clinical evidence of HRD as a *** review provides a blueprint for the standardization and harmonization of HRD assessments.

关键词： DNA damage response Homologous recombination repair deficiency Poly(ADP-ribose)polymerase inhibitor Biomarker Harmonization

Programmable endonuclease combined with isothermal polymerase amplification to selectively enrich for rare mutant allele fractions

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Chinese Chemical Letters 2022年第8期33卷 4126-4132页

作者： Junman Chen Tian Qiu Michael G.Mauk Zheng Su Yaguang Fan Dennis J.Yuan Qinghua Zhou Youlin Qiao Haim H.Bau jianming ying Jinzhao Song Key Laboratory of Clinical Laboratory Diagnostics(Ministry of Education) College of Laboratory MedicineChongqing Medical UniversityChongqing 400016China The Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital) Institute of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhou 310022China Department of Mechanical Engineering and Applied Mechanics University of PennsylvaniaPhiladelphiaPA 19104United States Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Center for Global Health School of Population Medicine and Public HealthChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment Tianjin Lung Cancer InstituteTianjin Medical University General HospitalTianjin 300052China Sichuan Lung Cancer Institute Sichuan Lung Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China

Liquid biopsy is a highly promising method for non-invasive detection of tumor-associated nucleic acid fragments in body fluids but is challenged by the low abundance of nucleic acids of clinical interest and their sequence homology with the vast background of nucleic acids from healthy ***,programmable endonucleases such as clustered regularly interspaced short palindromic repeats(CRISPR)associated protein(Cas)and prokaryotic Argonautes have been successfully used to remove background nucleic acids and enrich mutant allele fractions,enabling their detection with deep next generation sequencing(NGS).However,the enrichment level achievable with these assays is limited by futile binding events and off-target *** overcome these shortcomings,we conceived a new assay(Programmable Enzyme-Assisted Selective Exponential Amplification,PASEA)that combines the cleavage of wild type alleles with concurrent polymerase *** PASEA increases the numbers of both wild type and mutant alleles,the numbers of mutant alleles increase at much greater rates,allowing PASEA to achieve an unprecedented level of selective enrichment of targeted *** combining CRISPR-Cas9 based cleavage with recombinase polymerase amplification,we converted samples with0.01%somatic mutant allele fractions(MAFs)to products with 70%MAFs in a single step within 20 min,enabling inexpensive,rapid genotyping with such as Sanger ***,PASEA's extraordinary efficiency facilitates sensitive real-time detection of somatic mutant alleles at the point of care with custom designed Exo-RPA ***-time PASEA'performance was proved equivalent to clinical amplification refractory mutation system(ARMS)-PCR and NGS when testing over hundred cancer patients'*** strategy has the potential to reduce the cost and time of cancer screening and genotyping,and to enable targeted therapies in resource-limited settings.

关键词： Mutant allele enrichment Programmable endonuclease Liquid biopsy Mutation detection Point-of-care testing CRISPR-Cas9 Recombinase polymerase amplification Nucleic acid diagnostics

Clinicopathological features and surgical outcomes of four rare subtypes of primary liver carcinoma

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Chinese Journal of Cancer Research 2018年第3期30卷 364-372页

作者： Zhiyu Li Xiaolong Wu Xinyu Bi Yefan Zhang Zhen Huang Haizhen Lu Hong Zhao Jianjun Zhao Jianguo Zhou Muxing Li jianming ying Jianqiang Cai Department of Hepatobiliary Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College

Objective：This study aimed to analyze clinicopathological and prognostic features of four rare pathological subtypes of primary liver malignancies to make better understanding of their clinical ***：The clinicopathological data of 114 patients who were diagnosed with histologically proven four subtypes：clear cell carcinoma（CCC）,giant cell carcinoma（GCC）,sarcomatoid carcinoma（SC）,and combined hepatocellular-cholangiocarcinoma（CHC）between October 1998 and August 2015 were *** survival data were compared with those of 908 patients with histologically proven common hepatocellular carcinoma（HCC）（early-and advanced-stage HCC）during the same ***：The outcome of the CCC group was better than that of the other three subgroups,and was similar to that of the early-stage HCC ***,the smallest tumor size and the highest incidence of pseudocapsule formation were observed in the CCC *** SC group had the worst outcome among these four subgroups;the prognosis was much poorer than that of any other subgroups,even poorer than that of the advanced-stage common HCC *** statistical difference was observed between the GCC,CHC and advanced-stage HCC groups on survival *** incidences of tumor vascular emboli,TNM staging and non-radical resection were three risk factors of the ***：CCC is a low-degree malignancy and relatively favorably prognostic subtype of ***,GCC,SC,and CHC are three rare high-degree malignancy subtypes of HCC with poor prognosis.

关键词： Clear cell carcinoma combined hepatocellnlar-cholangiocarcinoma giant cell carcinoma sarcomatoid carcinoma hepatocellular carcinoma

Paeoniflorin alleviates depression by inhibiting the activation of NLRP3 inflammasome via promoting mitochondrial autophagy

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Chinese Journal of Natural Medicines 2024年第6期22卷 515-529页

作者： SU Lili GUO Pengli GUO Xiangjuan HE Zhongmei ZHAO Yan ZONG ying LI jianming CHEN Weijia DU Rui College of Chinese Medicinal Materials Jilin Agricultural UniversityChangchun 130118China Jilin Provincial Engineering Research Center for Efficient Breeding and Product Development of Sika Deer Changchun 130118China Key Laboratory of Animal Production and Product Quality and Security Ministry of EducationMinistry of National EducationChangchun 130118China

Depression ranks among the most common neuropsychiatric disorders *** studies examining the roles of inflammation and mitochondrial autophagy in the antidepressant efficacy of paeoniflorin(PF)are *** study aimed to elucidate PF’s antidepressant mechanism by promoting autophagy and inhibiting NLRP3 inflammasome activation using chronic unpredictable mild stimulation(CUMS)-induced C57BL/6 mouse models in vivo and corticosterone(CORT)-induced HT22 cell models in *** demonstrated that PF enhanced the viability of HT22 cells following CORT exposure,restored mitochondrial membrane poten-tial(MMP),reduced reactive oxygen species accumulation,increased LC3 fluorescence intensity,and suppressed inflammatory cy-tokine secretion and inflammation ***,PF ameliorated depressive behaviors induced by CUMS and improved damage in hippocampal *** also reduced the expression of NLRP3,ASC,Caspase-1,IL-1β,and the assembly of the NLRP3 ***,PF upregulated the expression of autophagy-related proteins in the hippocampus,facilitating the clearance of damaged mitochondria and enhancing *** role of autophagy in PF’s antidepressant effects was further confirmed through the use of the autophagy inhibitor 3-methyladenine(3-MA),which reduced the efficacy of *** conclusion,PF effectively improved depressive behaviors in CUMS-induced mice and reduced NLRP3-mediated inflammation both in vivo and in vitro,likely via the in-duction of autophagy.

关键词： Paeoniflorin Depression Autophagy NLRP3 inflammasome