BACKGROUND The log odds of positive lymph nodes(LODDS)are correlated with survival outcomes in gastric cancer(GC)patients.However,the prognostic value across different tumor differentiation levels remains unclear.AIM ...BACKGROUND The log odds of positive lymph nodes(LODDS)are correlated with survival outcomes in gastric cancer(GC)patients.However,the prognostic value across different tumor differentiation levels remains unclear.AIM To evaluate the independent prognostic value of LODDS and the stratified predictive efficacy in GC patients with different histologic differentiations.METHODS We conducted a retrospective analysis of 2103 GC patients who underwent radical gastrectomy at Zhejiang Cancer Hospital.The prognostic value of LODDS was compared with that of other lymph node-based metrics,including the pathologic N stage,number of positive lymph nodes,number of total lymph nodes,and lymph node ratio,stratified by tumor differentiation.RESULTS LODDS was identified as an independent prognostic factor for overall survival in moderately to poorly differentiated GC patients.LODDS demonstrated superior predictive accuracy over other lymph node metrics.A nomogram incorporating LODDS,age,carbohydrate antigen(CA)125,carcinoembryonic antigen,and tumor differentiation showed good predictive accuracy(C-index=0.703).A higher LODDS was significantly associated with an increased risk of recurrence or metastasis,poorly differentiated tumors,advanced cancer,mucinous gastric adenocarcinoma,nerve invasion,and vascular tumor thrombus.Additionally,LODDS was positively correlated with the tumor markers CA19-9,CA72-4,CA125,and CA242(all P<0.05).CONCLUSION LODDS is an independent prognostic indicator for patients with moderately and poorly differentiated GC,and its predictive performance is superior to that of other models.展开更多
BACKGROUND Gastric cancer(GC)is a highly prevalent gastrointestinal tract tumor.Several trials have demonstrated that the location of GC can affect patient prognosis.However,the factors determining tumor location rema...BACKGROUND Gastric cancer(GC)is a highly prevalent gastrointestinal tract tumor.Several trials have demonstrated that the location of GC can affect patient prognosis.However,the factors determining tumor location remain unclear.AIM To investigate the tumor location of patients,we went on to study the influencing factors that lead to changes in the location of GC.METHODS A retrospective evaluation was carried out on 3287 patients who underwent gastrectomy for GC in Zhejiang Cancer Hospital.The patients were followed up post-diagnosis and post-gastrectomy.The clinicopathological variables and overall survival of the patients were recorded.By analyzing the location of GC,the tumor location was divided into four categories:“Upper”,“middle”,“lower”,and“total”.Statistical software was utilized to analyze the relationship of each variable with the location of GC.RESULTS A total of 3287 patients were included in this study.The clinicopathological indices of gender,age,serum levels of carcinoembryonic antigen(CEA),carbohydrate antigen(CA19-9)and CA72-4 levels,were significantly associated with tumor location in patients with GC.In addition,there was a strong correlation between GC location and the prognosis of postoperative patients.Specifically,patients with“lower”and“middle”GC demonstrated a better prognosis than those with tumors in other categories.CONCLUSION The five clinicopathological indices of gender,age,CEA,CA19-9 and CA72-4 levels exhibit varying degrees of influence on the tumor location.The tumor location correlates with patient prognosis following surgery.展开更多
Poly(ADP-ribose)glycosylhydrolase(PARG)is an enzyme involved in hydrolyzing the ribose–ribose bonds present in poly(ADP-ribose)(PAR),which are primarily found in the nucleus.Along with poly(ADP-ribose)polymerase,PARG...Poly(ADP-ribose)glycosylhydrolase(PARG)is an enzyme involved in hydrolyzing the ribose–ribose bonds present in poly(ADP-ribose)(PAR),which are primarily found in the nucleus.Along with poly(ADP-ribose)polymerase,PARG regulates the level of PAR in cells,playing a crucial role in DNA maintenance and repair processes.Recent studies have revealed elevated levels of PARG in various cancers,such as breast,liver,prostate,and esophageal cancers,indicating a link to unfavorable cancer outcomes.PARG is a significant molecular target for treating PAR-related cancers.This review provides a comprehensive overview of the physiological role of PARG and the development of its inhibitors,highlighting its potential as an innovative target for cancer treatment.展开更多
Gastric signet ring cell carcinoma(GSRCC)is a distinct subtype of gastric cancer with unique epidemiological and pathogenic characteristics.However,its prognostic features and molecular landscape remain poorly underst...Gastric signet ring cell carcinoma(GSRCC)is a distinct subtype of gastric cancer with unique epidemiological and pathogenic characteristics.However,its prognostic features and molecular landscape remain poorly understood,limiting the development of targeted therapies.In this study,we analyzed clinical data from over 10,000 patients with gastric cancer treated at Zhejiang Cancer Hospital between January 2010 and December 2019.A comprehensive proteomic analysis was conducted on 112 GSRCC patients with a signet ring cell content exceeding 70%,identifying 7322 proteins.This study established a tissue-specific peptide spectral library,representing the most extensive proteomic atlas of GSRCC to date.We identified four novel proteomic subtypes:metabolism,microenvironment dysregulation,migration,and proliferation.Furthermore,PRDX2 and DDX27 emerged as potential prognostic biomarkers,which were further validated in an independent cohort of 75 patients.Molecular profiling of 79 cases that lacked expression of established gastric cancer treatment targets and biomarkers revealed significant tumor heterogeneity.Unsupervised clustering identified three distinct proteomic clusters,with cluster 2 exhibiting the poorest prognosis.Additionally,we identified four potential drug targets,including PFAS,EIF2S3,EIF6,and NFKB2.Molecular docking analysis suggested that neratinib,a clinically approved drug,could serve as a promising therapeutic agent for GSRCC,offering new avenues for clinical intervention.展开更多
基金Supported by the National Natural Science Foundation of China,No.82473195 and No.32370797the Natural Science Foundation of Zhejiang Province,No.LTGY23H160018+3 种基金the Zhejiang Medical and Health Science and Technology Program,No.2024KY789 and No.2023KY615the National Research Center for Translational Medicine at Shanghai Program,No.NRCTM(SH)-2025-07the Beijing Science and Technology Innovation Medical Development Foundation,No.KC2023-JX-0270-07the Key Laboratory of Prevention,Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province,No.2022E10021.
文摘BACKGROUND The log odds of positive lymph nodes(LODDS)are correlated with survival outcomes in gastric cancer(GC)patients.However,the prognostic value across different tumor differentiation levels remains unclear.AIM To evaluate the independent prognostic value of LODDS and the stratified predictive efficacy in GC patients with different histologic differentiations.METHODS We conducted a retrospective analysis of 2103 GC patients who underwent radical gastrectomy at Zhejiang Cancer Hospital.The prognostic value of LODDS was compared with that of other lymph node-based metrics,including the pathologic N stage,number of positive lymph nodes,number of total lymph nodes,and lymph node ratio,stratified by tumor differentiation.RESULTS LODDS was identified as an independent prognostic factor for overall survival in moderately to poorly differentiated GC patients.LODDS demonstrated superior predictive accuracy over other lymph node metrics.A nomogram incorporating LODDS,age,carbohydrate antigen(CA)125,carcinoembryonic antigen,and tumor differentiation showed good predictive accuracy(C-index=0.703).A higher LODDS was significantly associated with an increased risk of recurrence or metastasis,poorly differentiated tumors,advanced cancer,mucinous gastric adenocarcinoma,nerve invasion,and vascular tumor thrombus.Additionally,LODDS was positively correlated with the tumor markers CA19-9,CA72-4,CA125,and CA242(all P<0.05).CONCLUSION LODDS is an independent prognostic indicator for patients with moderately and poorly differentiated GC,and its predictive performance is superior to that of other models.
基金Supported by the National Natural Science Foundation of China,No.82473195Natural Science Foundation of Zhejiang Province,No.LTGY23H160018+2 种基金Zhejiang Medical and Health Science and Technology Program,No.2024KY789Beijing Science and Technology Innovation Medical Development Foundation,No.KC2023-JX-0270-07National Natural Science Foundation of China,No.32370797.
文摘BACKGROUND Gastric cancer(GC)is a highly prevalent gastrointestinal tract tumor.Several trials have demonstrated that the location of GC can affect patient prognosis.However,the factors determining tumor location remain unclear.AIM To investigate the tumor location of patients,we went on to study the influencing factors that lead to changes in the location of GC.METHODS A retrospective evaluation was carried out on 3287 patients who underwent gastrectomy for GC in Zhejiang Cancer Hospital.The patients were followed up post-diagnosis and post-gastrectomy.The clinicopathological variables and overall survival of the patients were recorded.By analyzing the location of GC,the tumor location was divided into four categories:“Upper”,“middle”,“lower”,and“total”.Statistical software was utilized to analyze the relationship of each variable with the location of GC.RESULTS A total of 3287 patients were included in this study.The clinicopathological indices of gender,age,serum levels of carcinoembryonic antigen(CEA),carbohydrate antigen(CA19-9)and CA72-4 levels,were significantly associated with tumor location in patients with GC.In addition,there was a strong correlation between GC location and the prognosis of postoperative patients.Specifically,patients with“lower”and“middle”GC demonstrated a better prognosis than those with tumors in other categories.CONCLUSION The five clinicopathological indices of gender,age,CEA,CA19-9 and CA72-4 levels exhibit varying degrees of influence on the tumor location.The tumor location correlates with patient prognosis following surgery.
基金supported by grants from the National Natural Science Foundation of China(32271485)the Natural Science Foundation of Zhejiang Province(YXD23H0302)to J.J.+3 种基金as well as grants from the National Natural Science Foundation of China(82473195)the Natural Science Foundation of Zhejiang Province(LTGY23H160018)the Zhejiang Medical and Health Science and Technology Program(2024KY789)the Beijing Science and Technology Innovation Medical Development Foundation(KC2023-JX-0270-07)to Z.Y.
文摘Poly(ADP-ribose)glycosylhydrolase(PARG)is an enzyme involved in hydrolyzing the ribose–ribose bonds present in poly(ADP-ribose)(PAR),which are primarily found in the nucleus.Along with poly(ADP-ribose)polymerase,PARG regulates the level of PAR in cells,playing a crucial role in DNA maintenance and repair processes.Recent studies have revealed elevated levels of PARG in various cancers,such as breast,liver,prostate,and esophageal cancers,indicating a link to unfavorable cancer outcomes.PARG is a significant molecular target for treating PAR-related cancers.This review provides a comprehensive overview of the physiological role of PARG and the development of its inhibitors,highlighting its potential as an innovative target for cancer treatment.
基金supported by the National Key Research and Development Program of China(No.2021YFA0910100,2021YFA0910101)the Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer(China)(No.JBZX-202006)+6 种基金the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(China)(No.ZYYCXTD-C-202208)the Medical Science and Technology Project of Zhejiang Province,China(No.WKJ-ZJ-2202,WKJ-ZJ-2104)the National Natural Science Foundation of China(No.82074245,81973634,82204828)the Natural Science Foundation of Zhejiang Province,China(No.QKHM25H3103,LHDMY22H160008)the Zhejiang Leading Innovation and Entrepreneurship Team(China)(No.2022R01006)the Pioneer R&D Program of Zhejiang,China(No.2024SDYXS0003,2023SDYXS0001)the Program of Zhejiang Provincial TCM Sci-Tech Plan(China)(No.GZY-ZJ-KJ-24064).
文摘Gastric signet ring cell carcinoma(GSRCC)is a distinct subtype of gastric cancer with unique epidemiological and pathogenic characteristics.However,its prognostic features and molecular landscape remain poorly understood,limiting the development of targeted therapies.In this study,we analyzed clinical data from over 10,000 patients with gastric cancer treated at Zhejiang Cancer Hospital between January 2010 and December 2019.A comprehensive proteomic analysis was conducted on 112 GSRCC patients with a signet ring cell content exceeding 70%,identifying 7322 proteins.This study established a tissue-specific peptide spectral library,representing the most extensive proteomic atlas of GSRCC to date.We identified four novel proteomic subtypes:metabolism,microenvironment dysregulation,migration,and proliferation.Furthermore,PRDX2 and DDX27 emerged as potential prognostic biomarkers,which were further validated in an independent cohort of 75 patients.Molecular profiling of 79 cases that lacked expression of established gastric cancer treatment targets and biomarkers revealed significant tumor heterogeneity.Unsupervised clustering identified three distinct proteomic clusters,with cluster 2 exhibiting the poorest prognosis.Additionally,we identified four potential drug targets,including PFAS,EIF2S3,EIF6,and NFKB2.Molecular docking analysis suggested that neratinib,a clinically approved drug,could serve as a promising therapeutic agent for GSRCC,offering new avenues for clinical intervention.
