Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial ...Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial diagnosis of disease, monitoring of disease progression, and identifying the mechanism of drug resistance. On behalf of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology(CSCO) and the China Actionable Genome Consortium(CAGC), the present expert group hereby proposes advisory guidelines on clinical applications of NGS technology for the analysis of cancer driver genes for precision cancer therapy. This group comprises an assembly of laboratory cancer geneticists, clinical oncologists, bioinformaticians,pathologists, and other professionals. After multiple rounds of discussions and revisions, the expert group has reached a preliminary consensus on the need of NGS in clinical diagnosis, its regulation, and compliance standards in clinical sample collection. Moreover, it has prepared NGS criteria, the sequencing standard operation procedure(SOP), data analysis, report, and NGS platform certification and validation.展开更多
Objective： Combined overall survival （OS） analysis of Lux-Lung 3 and Lux-Lung 6 demonstrated that patients with epidermal growth factor receptor （EGFR） exon 19 deletions （Del19） would benefit from first-line se...Objective： Combined overall survival （OS） analysis of Lux-Lung 3 and Lux-Lung 6 demonstrated that patients with epidermal growth factor receptor （EGFR） exon 19 deletions （Del19） would benefit from first-line second generation EGFR tyrosine kinase inhibitors （TKIs） afatinib but not for those with L858R. This study was to investigate the survival difference between first-line first generation EGFR-TKIs and chemotherapy in patients with either Del19 or L858R, and to directly compare OS in these two mutation groups. Methods： Eligibles were all prospective and retrospective studies comparing EGFR-TKIs with conventional chemotherapy or receiving single agent EGFR-TKIs and demonstrating survival analysis based on mutation types. The primary outcome was OS measured as pooled hazard ratios （HRs）. All measures were pooled using random- effects models and 95% confidential interval （95% CI） was calculated. Results： A total of 14 studies incorporating 1,706 patients with either Del19 or L858R were included. Enrolling patients with Del19 or L858R in randomized controlled trials （RCTs）, first-line first generation EGFR-TKIs were associated with no OS benefit, compared with chemotherapy （pooled HR_TKI/Chemo for Del19： 0.82, 95% CI： 0.64- 1.06, P=0.14; pooled HR_TKI/Chemo for L858R： 1.15, 95% CI： 0.85-1.56, P=0.38）. Direct comparison of Del19 with L858R receiving with first-line first generation EGFR-TKIs demonstrated no significant survival difference （pooled HR19/21： 0.88, 95% CI： 0.67-1.16, P=0.37）. Conclusions： Among patients with advanced non-small cell hmg cancer （NSCLC） harboring Del19 and L858R, first-line first generation EGFR-TKIs demonstrated no survival benefit comparing with chemotherapy. Direct comparison between Del19 and L858R revealed no significant survival difference after first-line first generation EGFR-TKIs.展开更多
Objective: To investigate whether laminin 5 (LN5) might be a predictor in lung cancer patient treated with gefitinib and estimate the underlying mechanisms. Methods: LN5 and epidermal growth factor receptor (EGFR) mRN...Objective: To investigate whether laminin 5 (LN5) might be a predictor in lung cancer patient treated with gefitinib and estimate the underlying mechanisms. Methods: LN5 and epidermal growth factor receptor (EGFR) mRNA expression level were detected in the tumor tissues of lung cancer patients who underwent surgery resection prior to gefitinib treatment. EGFR exon 19 and 21 mutation status was also detected in these specimens. The association between LN5, EGFR mRNA expression level, EGFR mutation and gefitinib treatment response were evaluated. In vitro study were carried by adding exog- enous LN5 and gefitinib to A549 lung cancer cell line, and Western-blotting was performed to investigate the phosphorylation level of EGFR,Ak, and Erk. Results: The disease control rate according to LN5 mRNA level was 52.9% for the below cut- point group, and 17.6% for the above cut-point (P = 0.009). The in vitro study showed that exogenous LN5 can neutralize the inhibition of phosphor-Akt by gefitinib. Conclusion: Patients with lower LN5 mRNA level would likely benefit from gefitinib. In vitro study indicated that the inhibition of Akt induced by gefitinib might be reversed by LN5. These results provide important insights into the molecular mechanisms underlying sensitivity to gefitinib in lung cancer patients.展开更多
Procalcitonin(PCT)is a widely used biomarker for the diagnosis of bacterial infections.It is produced by various organs and the liver is considered to be the most important site of production.Severe liver dysfunction ...Procalcitonin(PCT)is a widely used biomarker for the diagnosis of bacterial infections.It is produced by various organs and the liver is considered to be the most important site of production.Severe liver dysfunction has been shown to influence PCT levels.Patients with no sources of infection who have liver disease are observed to have increased serum levels of PCT,thereby reducing the diagnostic utility and value within this particular patient subset.Here,we have summarized the relationship between PCT and liver disease,including liver cirrhosis,liver failure,and liver transplantation.展开更多
Gene fusions and MET alterations are rare and difficult to detect in plasma samples.The clinical detection efficacy of molecular residual disease(MRD)based on circulating tumor DNA(ctDNA)in patients with non-small cel...Gene fusions and MET alterations are rare and difficult to detect in plasma samples.The clinical detection efficacy of molecular residual disease(MRD)based on circulating tumor DNA(ctDNA)in patients with non-small cell lung cancer(NSCLC)with these mutations remains unknown.This prospective,non-intervention study recruited 49 patients with operable NSCLC with actionable gene fusions(ALK,ROS1,RET,and FGFR1),MET exon 14 skipping or de novo MET amplification.We analyzed 43 tumor tissues and 111 serial perioperative plasma samples using 1021-and 338-gene panels,respectively.Detectable MRD correlated with a significantly higher recurrence rate(P<0.001),yielding positive predictive values of 100%and 90.9%,and negative predictive values of 82.4%and 86.4%at landmark and longitudinal time points,respectively.Patients with detectable MRD showed reduced disease-free survival(DFS)compared to those with undetectable MRD(P<0.001).Patients who harbored tissue-derived fusion/MET alterations in their MRD had reduced DFS compared to those who did not(P=0.05).To our knowledge,this is the first comprehensive study on ctDNA-MRD clinical detection efficacy in operable NSCLC patients with gene fusions and MET alterations.Patients with detectable tissue-derived fusion/MET alterations in postoperative MRD had worse clinical outcomes.展开更多
基金supported by grants from Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer (Grant No. 2017B030314120)General Research Project of Guangzhou Science and Technology Bureau (Grant No. 201607010391)+1 种基金National Key Research and Development Program of China (Grant No. 2016YFC1303800)Guangdong Provincial Applied S&T R&D Program (Grant No. 2016B020237006)
文摘Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial diagnosis of disease, monitoring of disease progression, and identifying the mechanism of drug resistance. On behalf of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology(CSCO) and the China Actionable Genome Consortium(CAGC), the present expert group hereby proposes advisory guidelines on clinical applications of NGS technology for the analysis of cancer driver genes for precision cancer therapy. This group comprises an assembly of laboratory cancer geneticists, clinical oncologists, bioinformaticians,pathologists, and other professionals. After multiple rounds of discussions and revisions, the expert group has reached a preliminary consensus on the need of NGS in clinical diagnosis, its regulation, and compliance standards in clinical sample collection. Moreover, it has prepared NGS criteria, the sequencing standard operation procedure(SOP), data analysis, report, and NGS platform certification and validation.
文摘Objective： Combined overall survival （OS） analysis of Lux-Lung 3 and Lux-Lung 6 demonstrated that patients with epidermal growth factor receptor （EGFR） exon 19 deletions （Del19） would benefit from first-line second generation EGFR tyrosine kinase inhibitors （TKIs） afatinib but not for those with L858R. This study was to investigate the survival difference between first-line first generation EGFR-TKIs and chemotherapy in patients with either Del19 or L858R, and to directly compare OS in these two mutation groups. Methods： Eligibles were all prospective and retrospective studies comparing EGFR-TKIs with conventional chemotherapy or receiving single agent EGFR-TKIs and demonstrating survival analysis based on mutation types. The primary outcome was OS measured as pooled hazard ratios （HRs）. All measures were pooled using random- effects models and 95% confidential interval （95% CI） was calculated. Results： A total of 14 studies incorporating 1,706 patients with either Del19 or L858R were included. Enrolling patients with Del19 or L858R in randomized controlled trials （RCTs）, first-line first generation EGFR-TKIs were associated with no OS benefit, compared with chemotherapy （pooled HR_TKI/Chemo for Del19： 0.82, 95% CI： 0.64- 1.06, P=0.14; pooled HR_TKI/Chemo for L858R： 1.15, 95% CI： 0.85-1.56, P=0.38）. Direct comparison of Del19 with L858R receiving with first-line first generation EGFR-TKIs demonstrated no significant survival difference （pooled HR19/21： 0.88, 95% CI： 0.67-1.16, P=0.37）. Conclusions： Among patients with advanced non-small cell hmg cancer （NSCLC） harboring Del19 and L858R, first-line first generation EGFR-TKIs demonstrated no survival benefit comparing with chemotherapy. Direct comparison between Del19 and L858R revealed no significant survival difference after first-line first generation EGFR-TKIs.
基金Supported by grants from the National Natural Science Foundation of China (No. 30772531)Guangdong Provincial Medical Science and Technology Research Foundation (No. B2006001)China Postdoc toral Science Foundation (No. 20060400212)
文摘Objective: To investigate whether laminin 5 (LN5) might be a predictor in lung cancer patient treated with gefitinib and estimate the underlying mechanisms. Methods: LN5 and epidermal growth factor receptor (EGFR) mRNA expression level were detected in the tumor tissues of lung cancer patients who underwent surgery resection prior to gefitinib treatment. EGFR exon 19 and 21 mutation status was also detected in these specimens. The association between LN5, EGFR mRNA expression level, EGFR mutation and gefitinib treatment response were evaluated. In vitro study were carried by adding exog- enous LN5 and gefitinib to A549 lung cancer cell line, and Western-blotting was performed to investigate the phosphorylation level of EGFR,Ak, and Erk. Results: The disease control rate according to LN5 mRNA level was 52.9% for the below cut- point group, and 17.6% for the above cut-point (P = 0.009). The in vitro study showed that exogenous LN5 can neutralize the inhibition of phosphor-Akt by gefitinib. Conclusion: Patients with lower LN5 mRNA level would likely benefit from gefitinib. In vitro study indicated that the inhibition of Akt induced by gefitinib might be reversed by LN5. These results provide important insights into the molecular mechanisms underlying sensitivity to gefitinib in lung cancer patients.
基金funded by the Fujian Medical Innovation Project(2016-cx-033)the Pilot Project of Fujian Science and Technology Department(2016Y0040,2017J01187)the Fujian Natural Science Foundation(2017J01187)
文摘Procalcitonin(PCT)is a widely used biomarker for the diagnosis of bacterial infections.It is produced by various organs and the liver is considered to be the most important site of production.Severe liver dysfunction has been shown to influence PCT levels.Patients with no sources of infection who have liver disease are observed to have increased serum levels of PCT,thereby reducing the diagnostic utility and value within this particular patient subset.Here,we have summarized the relationship between PCT and liver disease,including liver cirrhosis,liver failure,and liver transplantation.
基金supported by funding from the National Natural Science Foundation of China Major Joint Project on Key Scientific Issues of Lung Cancer(No.82241235)the National Natural Science Foundation of China(No.81872510)+3 种基金Guangdong Provincial People’s Hospital Young Talent Project(No.GDPPHYTP201902)Guangdong Basic and Applied Basic Research Foundation(No.2019B1515130002)High-level Hospital Construction Project(No.DFJH201801)Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer(No.2017B030314120).
文摘Gene fusions and MET alterations are rare and difficult to detect in plasma samples.The clinical detection efficacy of molecular residual disease(MRD)based on circulating tumor DNA(ctDNA)in patients with non-small cell lung cancer(NSCLC)with these mutations remains unknown.This prospective,non-intervention study recruited 49 patients with operable NSCLC with actionable gene fusions(ALK,ROS1,RET,and FGFR1),MET exon 14 skipping or de novo MET amplification.We analyzed 43 tumor tissues and 111 serial perioperative plasma samples using 1021-and 338-gene panels,respectively.Detectable MRD correlated with a significantly higher recurrence rate(P<0.001),yielding positive predictive values of 100%and 90.9%,and negative predictive values of 82.4%and 86.4%at landmark and longitudinal time points,respectively.Patients with detectable MRD showed reduced disease-free survival(DFS)compared to those with undetectable MRD(P<0.001).Patients who harbored tissue-derived fusion/MET alterations in their MRD had reduced DFS compared to those who did not(P=0.05).To our knowledge,this is the first comprehensive study on ctDNA-MRD clinical detection efficacy in operable NSCLC patients with gene fusions and MET alterations.Patients with detectable tissue-derived fusion/MET alterations in postoperative MRD had worse clinical outcomes.
