Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not ...Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully investigated.This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.Methods:A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled.HRD status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered HRD-positive.Genomic,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were analyzed.Results:Of the patients,25.1%(89/355)were HRD-positive.Compared to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(P<0.001),and fewer driver gene mutations(P<0.001).Furthermore,HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC.HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity.HRD-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T cells.HRD-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.Conclusions:Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC.Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC.This study highlights potential actionable alterations in HRD-positive NSCLC,suggesting possible combinational therapeutic strategies for these patients.展开更多
Objective:Histology grade,subtypes and TNM stage of lung adenocarcinomas are useful predictors of prognosis and survival.The aim of the study was to investigate the relationship between chromosomal instability,morphol...Objective:Histology grade,subtypes and TNM stage of lung adenocarcinomas are useful predictors of prognosis and survival.The aim of the study was to investigate the relationship between chromosomal instability,morphological subtypes and the grading system used in lung non-mucinous adenocarcinoma(LNMA).Methods:We developed a whole genome copy number variation(WGCNV)scoring system and applied next generation sequencing to evaluate CNVs present in 91 LNMA tumor samples.Results:Higher histological grades,aggressive subtypes and more advanced TNM staging were associated with an increased WGCNV score,particularly in CNV regions enriched for tumor suppressor genes and oncogenes.In addition,we demonstrate that 24-chromosome CNV profiling can be performed reliably from specific cell types(<100 cells)isolated by sample laser capture microdissection.Conclusions:Our findings suggest that the WGCNV scoring system we developed may have potential value as an adjunct test for predicting the prognosis of patients diagnosed with LNMA.展开更多
Objective： The relationship between anaplastic lymphoma kinase（ALK） expression in malignant pleural effusion（MPE） samples detected only by Ventana immunohistochemistry（IHC） ALK（D5F3） and the efficacy of ALKty...Objective： The relationship between anaplastic lymphoma kinase（ALK） expression in malignant pleural effusion（MPE） samples detected only by Ventana immunohistochemistry（IHC） ALK（D5F3） and the efficacy of ALKtyrosine kinase inhibitor therapy is uncertain.Methods： Ventana anti-ALK（D5F3） rabbit monoclonal primary antibody testing was performed on 313 cell blocks of MPE samples from Chinese patients with advanced lung adenocarcinoma, and fluorescence in situ hybridization（FISH） was used to verify the ALK gene status in Ventana IHC ALK（D5F3）-positive samples. The follow-up clinical data on patients who received crizotinib treatment were recorded.Results： Of the 313 MPE samples, 27（8.6%） were confirmed as ALK expression-positive, and the Ventana IHC ALK（D5F3）-positive rate was 17.3%（27/156） in wild-type epidermal growth factor receptor（EGFR） MPE samples. Twenty-three of the 27 IHC ALK（D5F3）-positive samples were positive by FISH. Of the 11 Ventana IHC ALK（D5F3）-positive patients who received crizotinib therapy, 2 patients had complete response（CR）, 5 had partial response（PR） and 3 had stable disease（SD）.Conclusions： The ALK gene expression status detected by the Ventana IHC ALK（D5F3） platform in MPE samples may predict tumor responsiveness to crizotinib in Chinese patients with advanced lung adenocarcinoma.展开更多
Based on DEA-Malmquist method,this paper calculated the integrated technology efficiency of grain production and total factor productivity and analyzed factors influencing the grain production technology efficiency us...Based on DEA-Malmquist method,this paper calculated the integrated technology efficiency of grain production and total factor productivity and analyzed factors influencing the grain production technology efficiency using working documents of panel structure. Research results indicate that grain production integrated technology efficiency of China is relatively low,technology utilization level is low,and it remains at the stage of decreasing returns to scale,and the pure technology efficiency still has space to increase. Total factor productivity is declining and the total factor productivity of many provinces is relatively low. Since the total factor productivity of eastern areas is higher than central and western areas,it is required to strengthen technological support for grain production. The implementation of urbanization is helpful for promoting increase of grain production technology efficiency in central and eastern areas,but it will exert negative influence on western areas.展开更多
基金supported by the National High Level Hospital Clinical Research Funding(No.BJ-2219-195 and No.BJ-2023-090).
文摘Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully investigated.This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.Methods:A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled.HRD status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered HRD-positive.Genomic,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were analyzed.Results:Of the patients,25.1%(89/355)were HRD-positive.Compared to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(P<0.001),and fewer driver gene mutations(P<0.001).Furthermore,HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC.HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity.HRD-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T cells.HRD-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.Conclusions:Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC.Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC.This study highlights potential actionable alterations in HRD-positive NSCLC,suggesting possible combinational therapeutic strategies for these patients.
基金grants from Beijing Hospital Key Research Program(121 Research Program,No.BJ2019-195)。
文摘Objective:Histology grade,subtypes and TNM stage of lung adenocarcinomas are useful predictors of prognosis and survival.The aim of the study was to investigate the relationship between chromosomal instability,morphological subtypes and the grading system used in lung non-mucinous adenocarcinoma(LNMA).Methods:We developed a whole genome copy number variation(WGCNV)scoring system and applied next generation sequencing to evaluate CNVs present in 91 LNMA tumor samples.Results:Higher histological grades,aggressive subtypes and more advanced TNM staging were associated with an increased WGCNV score,particularly in CNV regions enriched for tumor suppressor genes and oncogenes.In addition,we demonstrate that 24-chromosome CNV profiling can be performed reliably from specific cell types(<100 cells)isolated by sample laser capture microdissection.Conclusions:Our findings suggest that the WGCNV scoring system we developed may have potential value as an adjunct test for predicting the prognosis of patients diagnosed with LNMA.
基金supported by grants from the Beijing Municipal Science and Technology Commission(D141100000214003)the Natural Science Foundation of China(No.81641114)
文摘Objective： The relationship between anaplastic lymphoma kinase（ALK） expression in malignant pleural effusion（MPE） samples detected only by Ventana immunohistochemistry（IHC） ALK（D5F3） and the efficacy of ALKtyrosine kinase inhibitor therapy is uncertain.Methods： Ventana anti-ALK（D5F3） rabbit monoclonal primary antibody testing was performed on 313 cell blocks of MPE samples from Chinese patients with advanced lung adenocarcinoma, and fluorescence in situ hybridization（FISH） was used to verify the ALK gene status in Ventana IHC ALK（D5F3）-positive samples. The follow-up clinical data on patients who received crizotinib treatment were recorded.Results： Of the 313 MPE samples, 27（8.6%） were confirmed as ALK expression-positive, and the Ventana IHC ALK（D5F3）-positive rate was 17.3%（27/156） in wild-type epidermal growth factor receptor（EGFR） MPE samples. Twenty-three of the 27 IHC ALK（D5F3）-positive samples were positive by FISH. Of the 11 Ventana IHC ALK（D5F3）-positive patients who received crizotinib therapy, 2 patients had complete response（CR）, 5 had partial response（PR） and 3 had stable disease（SD）.Conclusions： The ALK gene expression status detected by the Ventana IHC ALK（D5F3） platform in MPE samples may predict tumor responsiveness to crizotinib in Chinese patients with advanced lung adenocarcinoma.
基金Supported by Project of National Natural Science Foundation(71373215)Key Project of Fundamental Research Funds for Southwest University(SWU1309003)Fundamental Research Funds for the Central Universities in 2015(SWU1509317)
文摘Based on DEA-Malmquist method,this paper calculated the integrated technology efficiency of grain production and total factor productivity and analyzed factors influencing the grain production technology efficiency using working documents of panel structure. Research results indicate that grain production integrated technology efficiency of China is relatively low,technology utilization level is low,and it remains at the stage of decreasing returns to scale,and the pure technology efficiency still has space to increase. Total factor productivity is declining and the total factor productivity of many provinces is relatively low. Since the total factor productivity of eastern areas is higher than central and western areas,it is required to strengthen technological support for grain production. The implementation of urbanization is helpful for promoting increase of grain production technology efficiency in central and eastern areas,but it will exert negative influence on western areas.
