Adenosquamous carcinoma of the pancreas(ASCP)is a rare histological subtype of pancreatic cancer with a poor prognosis and a high metastasis rate.However,little is known about its genomic landscape and prognostic biom...Adenosquamous carcinoma of the pancreas(ASCP)is a rare histological subtype of pancreatic cancer with a poor prognosis and a high metastasis rate.However,little is known about its genomic landscape and prognostic biomarkers.A total of 48 ASCP specimens and 98 pancreatic ductal adenocarcinoma(PDAC)tumour specimens were sequenced to explore the genomic landscape and prognostic biomarkers.The homozygous deletion of the 9p21.3 region(including CDKN2A,CDKN2B,and MTAP)(9p21 loss)occurred in both ASCP and PDAC,and a higher frequency of 9p21 loss was observed in ASCP(12.5%vs 2.0%,P=0.022).Notably,9p21 loss was significantly associated with poor disease-free survival(DFS)in ASCP patients(mDFS(Median DFS)=4.17 vs 7.33 months,HR(Hazard Ratio)=3.70,P=0.009).The most common gene alterations in patients with ASCP were KRAS(96%),TP53(81%),CDKN2A(42%),SMAD4(21%),CDKN2B(13%),and FAT3(13%).The mutation rates of ACVR2A(6.25%vs 0%),FANCA(6.25%vs 0%),RBM10(6.25%vs 0%),and SPTA1(8.33%vs 1.02%)were significantly higher in ASCP than in PDAC.In conclusion,we have comprehensively described the genomic landscape of the largest cohort of ASCP patients to date and highlight that 9p21 loss may be a promising prognostic biomarker for ASCP,which provides a molecular basis for prognosis prediction and new therapeutic strategies for ASCP.展开更多
The Arctic has experienced several extreme springtime stratospheric ozone depletion events over the past four decades,particularly in 1997,2011 and 2020.However,the impact of this stratospheric ozone depletion on the ...The Arctic has experienced several extreme springtime stratospheric ozone depletion events over the past four decades,particularly in 1997,2011 and 2020.However,the impact of this stratospheric ozone depletion on the climate system remains poorly understood.Here we show that the stratospheric ozone depletion causes significant reductions in the sea ice concentration(SIC)and the sea ice thickness(SIT)over the Kara Sea,Laptev Sea and East Siberian Sea from spring to summer.This is partially caused by enhanced ice transport from Barents-Kara Sea and East Siberian Sea to the Fram Strait,which is induced by a strengthened and longer lived polar vortex associated with stratospheric ozone depletion.Additionally,cloud longwave radiation and surface albedo feedbacks enhance the melting of Arctic sea ice,particularly along the coast of the Eurasian continent.This study highlights the need for realistic representation of stratosphere-troposphere interactions in order to accurately predict Arctic sea ice loss.展开更多
基金supported by the National Natural Science Foundation of China(Grants No.81872008,82072702)Shanxi Provincial Grant of Scientific and Technological Innovation Team(Grant No.2022-TD-43)+1 种基金Youth Innovation Team Project of Xi’an Jiaotong University(Grant No.2022-TD-007)Clinical Research Award of the First Affiliated Hospital of Xi’an Jiaotong University,China(Grant No.XJTU1AF-CRF-2019–005).
文摘Adenosquamous carcinoma of the pancreas(ASCP)is a rare histological subtype of pancreatic cancer with a poor prognosis and a high metastasis rate.However,little is known about its genomic landscape and prognostic biomarkers.A total of 48 ASCP specimens and 98 pancreatic ductal adenocarcinoma(PDAC)tumour specimens were sequenced to explore the genomic landscape and prognostic biomarkers.The homozygous deletion of the 9p21.3 region(including CDKN2A,CDKN2B,and MTAP)(9p21 loss)occurred in both ASCP and PDAC,and a higher frequency of 9p21 loss was observed in ASCP(12.5%vs 2.0%,P=0.022).Notably,9p21 loss was significantly associated with poor disease-free survival(DFS)in ASCP patients(mDFS(Median DFS)=4.17 vs 7.33 months,HR(Hazard Ratio)=3.70,P=0.009).The most common gene alterations in patients with ASCP were KRAS(96%),TP53(81%),CDKN2A(42%),SMAD4(21%),CDKN2B(13%),and FAT3(13%).The mutation rates of ACVR2A(6.25%vs 0%),FANCA(6.25%vs 0%),RBM10(6.25%vs 0%),and SPTA1(8.33%vs 1.02%)were significantly higher in ASCP than in PDAC.In conclusion,we have comprehensively described the genomic landscape of the largest cohort of ASCP patients to date and highlight that 9p21 loss may be a promising prognostic biomarker for ASCP,which provides a molecular basis for prognosis prediction and new therapeutic strategies for ASCP.
基金supported by Project of Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)(SML2021SP312)the National Natural Science Foundation of China(4207506242130601,and 41922044)+3 种基金the National Key Research&Development Program of China(2018YFC1506003)the Fundamental Research Funds for the Central Universities,China(lzujbky-2021ey04)Young Doctoral Funds for Gansu Provincial Education Department(2021QB-009)supported by Supercomputing Center of Lanzhou University。
文摘The Arctic has experienced several extreme springtime stratospheric ozone depletion events over the past four decades,particularly in 1997,2011 and 2020.However,the impact of this stratospheric ozone depletion on the climate system remains poorly understood.Here we show that the stratospheric ozone depletion causes significant reductions in the sea ice concentration(SIC)and the sea ice thickness(SIT)over the Kara Sea,Laptev Sea and East Siberian Sea from spring to summer.This is partially caused by enhanced ice transport from Barents-Kara Sea and East Siberian Sea to the Fram Strait,which is induced by a strengthened and longer lived polar vortex associated with stratospheric ozone depletion.Additionally,cloud longwave radiation and surface albedo feedbacks enhance the melting of Arctic sea ice,particularly along the coast of the Eurasian continent.This study highlights the need for realistic representation of stratosphere-troposphere interactions in order to accurately predict Arctic sea ice loss.