Objective:Long-term survivors(LS)of non-small cell lung cancer(NSCLC)without driver alterations,displaying an overall survival(OS)of more than 3 years,comprise around 10%of cases in several series treated with chemoth...Objective:Long-term survivors(LS)of non-small cell lung cancer(NSCLC)without driver alterations,displaying an overall survival(OS)of more than 3 years,comprise around 10%of cases in several series treated with chemotherapy.There are classical prognosis factors for these cases[stage,Eastern Cooperative Oncology Group(ECOG),etc.],but more data are required in the literature.In this multi-center study,we focused on LS of advanced NSCLC with OS above 36 months to perform a clinical-pathological and molecular characterization.Methods:In the first step,we conducted a clinical-pathological characterization of the patients.Afterwards,we carried out a genetic analysis by comparing LS to a sample of short-term survivors(SS)(with an OS less than 9 months).We initially used whole-genome RNA-seq to identify differentiating profiles of LS and SS,and later confirmed these with reverse transcription-polymerase chain reaction(RT-PCR)for the rest of the samples.Results:A total of 94 patients were included,who were mainly men,former smokers,having adenocarcinoma(AC)-type NSCLC with an ECOG of 0-1.We obtained an initial differential transcriptome expression,displaying 5 over-and 33 under-expressed genes involved in different pathways:namely,the secretin receptor,surfactant protein,trefoil factor 1(T FF1),serpin,Ca-channels,and Tolllike receptor(TLRs)families.Finally,RT-PCR analysis of 40(20 LS/20 SS)samples confirmed that four genes(surfactant proteins and SFTP)were significantly down-regulated in SS compared to LS by using an analysis of covariance(ANCOVA)model:SFTPA1(P=0.023),SFTPA2(P=0.027),SFTPB{P=0.02),and SFT PC(P=0.047).Conclusions:We present a sequential genetic analysis of a sample of NSCLCLS with no driver alterations,obtaining a differential RNA-seq/RT-PCR profile showing an abnormal expression of SF genes.展开更多
Infection is currently one of the main contributors to carcinogenesis.In fact,the International Agency for Research on Cancer has categorized eleven biological agents as group I carcinogens.It is estimated that around...Infection is currently one of the main contributors to carcinogenesis.In fact,the International Agency for Research on Cancer has categorized eleven biological agents as group I carcinogens.It is estimated that around 16%of the 12.7 million new cancers diagnosed in 2008 were attributable to infectious agents.Although underdeveloped regions carry the highest incidence rates,about 7.4%of infectionrelated cancer cases occur in developed areas.Physicians are increasingly aware of the potential carcinogenic role of common virus like the Human Papilloma virus in cervical cancer,or the hepatitis B and C viruses in hepatocarcinoma.However,the carcinogenic role of several other infectious agents is less recognized.Given that gastrointestinal malignancies carry an overall poor prognosis,a better understanding of the carcinogenic mechanisms triggered by infectious agents is key to decrease the rate of cancer related deaths.Preventive measures directed to such infections would ideally impact survival.In this paper we review the main pathogenic mechanisms related to the development of gastrointestinal malignancies induced by infectious microorganisms and other pathogens which are currently under investigation.展开更多
基金the following groups for aiding in the creation of this study:all the patients and their families for permitting the review of all the information included in this study,the“day hospital”workers from all the hospitals involved,the Carlos III Health Institute,the IMDEA Research Institute on Food 8c Health Sciences,the Spanish Ministry of Science(Plan Nacional I+D+i AGL2016-76736-C3)the Regional Government of Community of Madrid(S2018/BAA-4343)the Ramon Areces Foundation,the EU Structural Funds and the AECC(Spanish Association Against Cancer).Thanks to Scribendi editing and proofreading services for final manuscript review.
文摘Objective:Long-term survivors(LS)of non-small cell lung cancer(NSCLC)without driver alterations,displaying an overall survival(OS)of more than 3 years,comprise around 10%of cases in several series treated with chemotherapy.There are classical prognosis factors for these cases[stage,Eastern Cooperative Oncology Group(ECOG),etc.],but more data are required in the literature.In this multi-center study,we focused on LS of advanced NSCLC with OS above 36 months to perform a clinical-pathological and molecular characterization.Methods:In the first step,we conducted a clinical-pathological characterization of the patients.Afterwards,we carried out a genetic analysis by comparing LS to a sample of short-term survivors(SS)(with an OS less than 9 months).We initially used whole-genome RNA-seq to identify differentiating profiles of LS and SS,and later confirmed these with reverse transcription-polymerase chain reaction(RT-PCR)for the rest of the samples.Results:A total of 94 patients were included,who were mainly men,former smokers,having adenocarcinoma(AC)-type NSCLC with an ECOG of 0-1.We obtained an initial differential transcriptome expression,displaying 5 over-and 33 under-expressed genes involved in different pathways:namely,the secretin receptor,surfactant protein,trefoil factor 1(T FF1),serpin,Ca-channels,and Tolllike receptor(TLRs)families.Finally,RT-PCR analysis of 40(20 LS/20 SS)samples confirmed that four genes(surfactant proteins and SFTP)were significantly down-regulated in SS compared to LS by using an analysis of covariance(ANCOVA)model:SFTPA1(P=0.023),SFTPA2(P=0.027),SFTPB{P=0.02),and SFT PC(P=0.047).Conclusions:We present a sequential genetic analysis of a sample of NSCLCLS with no driver alterations,obtaining a differential RNA-seq/RT-PCR profile showing an abnormal expression of SF genes.
文摘Infection is currently one of the main contributors to carcinogenesis.In fact,the International Agency for Research on Cancer has categorized eleven biological agents as group I carcinogens.It is estimated that around 16%of the 12.7 million new cancers diagnosed in 2008 were attributable to infectious agents.Although underdeveloped regions carry the highest incidence rates,about 7.4%of infectionrelated cancer cases occur in developed areas.Physicians are increasingly aware of the potential carcinogenic role of common virus like the Human Papilloma virus in cervical cancer,or the hepatitis B and C viruses in hepatocarcinoma.However,the carcinogenic role of several other infectious agents is less recognized.Given that gastrointestinal malignancies carry an overall poor prognosis,a better understanding of the carcinogenic mechanisms triggered by infectious agents is key to decrease the rate of cancer related deaths.Preventive measures directed to such infections would ideally impact survival.In this paper we review the main pathogenic mechanisms related to the development of gastrointestinal malignancies induced by infectious microorganisms and other pathogens which are currently under investigation.