Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damag...Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damage exerted by platinum agents.Alteration in this repair mechanism may affect patients’survival.Materials and Methods:We conducted a retrospective analysis of data from 38 patients with extensive disease(ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit,Careggi University Hospital,Florence(Italy),from 2015 to 2020.mRNA expression analysis and single nucleotide polymorphism(SNP)characterization of three NER pathway genes—namely ERCC1,ERCC2,and ERCC5—were performed on patient tumor samples.Results:Overall,elevated expression of ERCC genes was observed in SCLC patients compared to healthy controls.Patients with low ERCC1 and ERCC5 expression levels exhibited a better median progression-free survival(mPFS=7.1 vs.4.9 months,p=0.39 for ERCC1 and mPFS=6.9 vs.4.8 months,p=0.093 for ERCC5)and overall survival(mOS=8.7 vs.6.0 months,p=0.4 for ERCC1 and mOS=7.2 vs.6.2 months,p=0.13 for ERCC5).Genotyping analysis of five SNPs of ERCC genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the ERCC1 rs11615 SNP(p=0.24 for PFS and p=0.14 for OS)and of the rs13181 and rs1799793 ERCC2 SNPs(p=0.43 and p=0.26 for PFS and p=0.21 and p=0.16 for OS,respectively)compared to patients with homozygous mutant genotypes.Conclusions:The comprehensive analysis of ERCC gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.展开更多
High-throughput genotyping tools can effectively promote molecular breeding in crops.In this study,genotyping by target sequencing(GBTS)system was utilized to develop a genome-wide liquid SNP chip for facilitating gen...High-throughput genotyping tools can effectively promote molecular breeding in crops.In this study,genotyping by target sequencing(GBTS)system was utilized to develop a genome-wide liquid SNP chip for facilitating genetics and breeding in melon(Cucumis melo L.),a globally cultivated economically important horticultural crop.Based on over eight million SNPs derived from 823 representative melon accessions,16K,8K,4K,2K,1K,500,250 and 125 informative SNPs were screened and evaluated for their polymorphisms,conservation of flanking sequences,and distributions.The set of 2K SNPs was found to be optimal for representing the maximum diversity with the lowest number of SNPs,and it was selected to develop the liquid chip,named“Melon2K”.Using Melon2K,more than 1500 SNPs were detected across 17 samples of five melon cultivars,and the phylogenetic relationships were clearly constructed.Within the same cultivar,genetic differences were also assessed between different samples.We evaluated the performance of Melon2K in genetic background selection during the breeding process,obtaining the introgression lines of interested trait with more than 97%genetic background of elite variety by only two rounds of backcrossing.These results suggest that Melon2K provides a cost-effective,efficient and reliable platform for genetic analysis and molecular breeding in melon.展开更多
文摘Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damage exerted by platinum agents.Alteration in this repair mechanism may affect patients’survival.Materials and Methods:We conducted a retrospective analysis of data from 38 patients with extensive disease(ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit,Careggi University Hospital,Florence(Italy),from 2015 to 2020.mRNA expression analysis and single nucleotide polymorphism(SNP)characterization of three NER pathway genes—namely ERCC1,ERCC2,and ERCC5—were performed on patient tumor samples.Results:Overall,elevated expression of ERCC genes was observed in SCLC patients compared to healthy controls.Patients with low ERCC1 and ERCC5 expression levels exhibited a better median progression-free survival(mPFS=7.1 vs.4.9 months,p=0.39 for ERCC1 and mPFS=6.9 vs.4.8 months,p=0.093 for ERCC5)and overall survival(mOS=8.7 vs.6.0 months,p=0.4 for ERCC1 and mOS=7.2 vs.6.2 months,p=0.13 for ERCC5).Genotyping analysis of five SNPs of ERCC genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the ERCC1 rs11615 SNP(p=0.24 for PFS and p=0.14 for OS)and of the rs13181 and rs1799793 ERCC2 SNPs(p=0.43 and p=0.26 for PFS and p=0.21 and p=0.16 for OS,respectively)compared to patients with homozygous mutant genotypes.Conclusions:The comprehensive analysis of ERCC gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.
基金supported by the National Natural Science Foundation of China(Grant Nos.32102383,32225044 and 32130093)the Natural Science Foundation of Shandong Province(Grant No.ZR2021QC075)+1 种基金the Taishan Scholar Foundation of the People's Government of Shandong Province(Grant No.ts20190947)the Qingdao Agricultural University Doctoral Start-Up Fund。
文摘High-throughput genotyping tools can effectively promote molecular breeding in crops.In this study,genotyping by target sequencing(GBTS)system was utilized to develop a genome-wide liquid SNP chip for facilitating genetics and breeding in melon(Cucumis melo L.),a globally cultivated economically important horticultural crop.Based on over eight million SNPs derived from 823 representative melon accessions,16K,8K,4K,2K,1K,500,250 and 125 informative SNPs were screened and evaluated for their polymorphisms,conservation of flanking sequences,and distributions.The set of 2K SNPs was found to be optimal for representing the maximum diversity with the lowest number of SNPs,and it was selected to develop the liquid chip,named“Melon2K”.Using Melon2K,more than 1500 SNPs were detected across 17 samples of five melon cultivars,and the phylogenetic relationships were clearly constructed.Within the same cultivar,genetic differences were also assessed between different samples.We evaluated the performance of Melon2K in genetic background selection during the breeding process,obtaining the introgression lines of interested trait with more than 97%genetic background of elite variety by only two rounds of backcrossing.These results suggest that Melon2K provides a cost-effective,efficient and reliable platform for genetic analysis and molecular breeding in melon.
