Clonal hematopoiesis(CH)is a clonally expanded population of hematopoietic stem cells carrying somatic mutations that differentiate through multilineage hematopoiesis to form terminally differentiated mature hematopoi...Clonal hematopoiesis(CH)is a clonally expanded population of hematopoietic stem cells carrying somatic mutations that differentiate through multilineage hematopoiesis to form terminally differentiated mature hematopoietic cells carrying markers of the clonal mutation.Genes integral to critical cellular processes such as epigenetic regulation,DNA damage response,and inflammation frequently carry these mutations.Clonal hematopoiesis becomes increasingly prevalent with age and is associated with an increased risk of hematological tumors and some nonhematological conditions.Recent insights have revealed that the mutations driving CH are not only implicated in hematologic neoplasms but also possess the potential to influence cardiovascular pathogenesis.Here,we reviewed up-to-date findings about the roles of CH in cardiovascular diseases and tumors and explored the clinical significance of CH,as well as look forward to future related studies,so as to provide valuable references for future research and clinical practice.展开更多
This review is part two of three, which will present an update on the classification of gastrointestinal submucosal tumors. Part one treats of the diagnosis and part three of the therapeutic methods regarding gastroin...This review is part two of three, which will present an update on the classification of gastrointestinal submucosal tumors. Part one treats of the diagnosis and part three of the therapeutic methods regarding gastrointestinal submucosal tumors. In the past there has been some confusion as to the classification of gastrointestinal submucosal tumors. Changes in classifications have emerged due to recent advances in mainly immunohistochemistry and electron microscopy. The aim of this paper is to update the reader on the current classification. Literature searches were performed to find information related to classification of gastrointestinal submucosal tumors. Based on these searches the twelve most frequent submucosal tumor types were chosen for description of their classification. The factors that indicate whether tumors are benign or malignant are mainly size and number of mitotic counts. Gastrointestinal stromal tumors are defined mainly by their CD117 positivity. In the future, there should be no more confusion between gastrointestinal stromal tumors and other types of submucosal tumors.2007 The WJG Press. All rights reserved.展开更多
Background:Combined hepatocellular and cholangiocarcinoma(CHC) is a unique subtype of liver cancer comprising both hepatocellular carcinoma(HCC) and intrahepatic cholangiocarcinoma(ICC);however,its cellular origin rem...Background:Combined hepatocellular and cholangiocarcinoma(CHC) is a unique subtype of liver cancer comprising both hepatocellular carcinoma(HCC) and intrahepatic cholangiocarcinoma(ICC);however,its cellular origin remains unclear.The purpose of this study was to investigate the clinicopathologic features and the clonal relationship between HCC and ICC in 34 patients with CHC.Methods:The clinicopathologic features and prognosis of the 34 CHC patients were compared with those of 29 patients with separated HCC and ICC(5HC).Loss of heterozygosity(LOH) at 10 highly polymorphic microsatellite markers was detected in 16 CHC and 10 SHC tissues for determination of the clonal origin of CHC.Expression of hepatocyte markers[hepatocyte paraffin 1(Hep Par 1) and glypican 3(GPC3)]and cholangiocyte markers[cytokeratin(CK)7 and 19]in tumor tissues was examined by immuno histochemical analysis.Results:In the 16 CHC specimens,the difference in LOH patterns between HCC and ICC was less than 30%,suggesting the same clonal origin of HCC and ICC.Consistent with this finding,immunohistochemical analysis revealed that hepatocyte markers(Hep Par 1 and GPC3) and cholangiocyte markers(CK7 and CK19) were simultaneously expressed in both the HCC and ICC components in 52.9%of CHC specimens,suggesting that the two components shared a similar phenotype with hepatic progenitor cells(HPCs).On the contrary,in all 10 SHC cases,the difference in LOH patterns between the HCC and ICC components was greater than 30%,suggesting different clonal origins of HCC and ICC.Overall survival and disease-free survival were shorter for patients with CHC than for patients with SHC(P < 0.05).Conclusions:Our results suggest that the HCC and ICC components of CHC may originate from the same clone,having the potential for dual-directional differentiation similar to HPCs.CHC tended to exhibit the biological behaviors of both HCC and ICC,which may enhance the infiltrative capacity of tumor cells,leading to poor clinical outcomes for patients with CHC.展开更多
AIM To observe the natural course of 1-3 cm gastric submucosal tumors originating from the muscularis propria(SMTMPs).METHODS By reviewing the computerized medical records over a period of 14 years(2000-2013), patient...AIM To observe the natural course of 1-3 cm gastric submucosal tumors originating from the muscularis propria(SMTMPs).METHODS By reviewing the computerized medical records over a period of 14 years(2000-2013), patients with 1-3 cm gastric SMTMPs who underwent at least two endoscopic ultrasound(EUS) examinations were enrolled. Tumor progression was defined as a ≥ 1.2 times enlargement in tumor diameter observed during EUS surveillance. All patients were divided into stationary and progressive subgroups and further analyzed. We also reviewed the patients in the progressive subgroup again in 2016.RESULTS A total of 88 patients were studied, including 25 in the progressive subgroup. The mean time of EUS surveillance was 24.6 mo in the stationary subgroup and 30.7 mo in the progressive subgroup. Risk factors for tumor progression included larger tumor size and irregular border. Initial tumor size > 14.0 mm may be considered a cut-off size for predicting tumor progression. Seventeen patients underwent surgery, of whom 13 had gastrointestinal stromal tumors(GISTs) and 4 had leiomyomas. Tumor progression was found only in patients with GISTs. All of the tumors exhibited benign behaviors without metastasis until 2016.CONCLUSION Most 1-3 cm gastric SMTMPs(71.6%) are indolent. Tumor progression was found only in GISTs, and it is a good predictor for differentiating GISTs from leiomyomas. Predictors of tumor progression include larger tumor size(> 14.0 mm) and irregular border.展开更多
Objective: Multiple mechanisms underlying the development of portal vein tumor thrombus(PVTT) in hepatocellular carcinoma(HCC) have been reported recently. However, the origins of PVTT remain unknown. Increasing multi...Objective: Multiple mechanisms underlying the development of portal vein tumor thrombus(PVTT) in hepatocellular carcinoma(HCC) have been reported recently. However, the origins of PVTT remain unknown. Increasing multi-omics data on PVTTs in HCCs have made it possible to investigate whether PVTTs originate from the corresponding primary tumors(Ts).Methods: The clonal relationship between PVTTs and their corresponding primary Ts was investigated using datasets deposited in public databases. One DNA copy number variations dataset and three gene expression datasets were downloaded for the analyses.Clonality analysis was performed to investigate the clonal relationship between PVTTs and Ts from an individual patient.Differential gene expression analysis was applied to investigate the gene expression profiles of PVTTs and Ts.Results: One out of 19 PVTTs had no clonal relationship with its corresponding T, whereas the others did. The PVTTs with independent clonal origin showed different gene expression and enrichment in biological processes from the primary Ts. Based on the unique gene expression profiles, a gene signature including 24 genes was used to identify pairs of PVTTs and primary Ts without any clonal relationship. Validation in three datasets showed that these types of pairs of PVTTs and Ts can be identified by the 24-gene signature.Conclusions: Our findings show a direct evidence for PVTT origin and consolidate the heterogeneity of PVTTs observed in clinic.The results suggest that PVTT investigation at a molecular level is clinically necessary for diagnosis and treatment.展开更多
Collision tumors are thought to arise from the accidental meeting and interpenetration of two independent tumors. We report here a highly unusual case of a 61-year old man who had a unique tumor that was composed of a...Collision tumors are thought to arise from the accidental meeting and interpenetration of two independent tumors. We report here a highly unusual case of a 61-year old man who had a unique tumor that was composed of a metastatic adenocarcinoma from the stomach to the rectum, which harbored a collision tumor of primary rectal adenocarcinoma. The clonalities of the two histologically distinct lesions of the rectal mass were confirmed by immunohistochemical and molecular analysis. Although histologic examination is the cornerstone in pathology, immunohistochemical and molecular analysis can provide evidence regarding whether tumors originate from the same clone or different clones. To the best of our knowledge, this is the fi rst reported case of such an occurrence.展开更多
Objective:The high post-operative recurrence of hepatocellular carcinoma(RHCC)and multinodular hepatocellular carcinoma(MHCC)seriously limit the surgical efficacy of HCC.Theoretically,RHCC/MHCC arise from either resid...Objective:The high post-operative recurrence of hepatocellular carcinoma(RHCC)and multinodular hepatocellular carcinoma(MHCC)seriously limit the surgical efficacy of HCC.Theoretically,RHCC/MHCC arise from either residual tumor cells or novel clone-derived tumor cells which have a great impact on designing personalized therapies and the evaluation of clinical long-term outcome.展开更多
Objective: Neoantigens derived from tumor-specific genomic alterations have demonstrated great potential for immunotherapeutic interventions in cancers. However, the comprehensive profile of hepatocellular carcinoma(H...Objective: Neoantigens derived from tumor-specific genomic alterations have demonstrated great potential for immunotherapeutic interventions in cancers. However, the comprehensive profile of hepatocellular carcinoma(HCC) neoantigens and their complex interplay with immune microenvironment and tumor evolution have not been fully addressed.Methods: Here we integrated whole exome sequencing data, transcriptome sequencing data and clinical information of 72 primary HCC patients to characterize the HCC neoantigen profile, and systematically explored its interactions with tumor clonal evolution, driver mutations and immune microenvironments.Results: We observed that higher somatic mutation/neoantigen load was associated with better clinical outcomes and HCC patients could be further divided into two subgroups with distinct prognosis based on their neoantigen expression patterns. HCC subgroup with neoantigen expression probability high(NEP-H) showed more aggressive pathologic features including increased incidence of tumor thrombus(P=0.038), higher recurrence rate(P=0.029),more inclined to lack tumor capsule(P=0.026) and with more microsatellite instability sites(P=0.006). In addition,NEP-H subgroup was also characterized by higher chance to be involved in tumor clonal evolution [odds ratio(OR)=46.7, P<0.001]. Gene set enrichment analysis revealed that upregulation of MYC and its targets could suppress immune responses, leading to elevated neoantigen expression proportion in tumor cells. Furthermore, we discovered an immune escape mechanism that tumors could become more inconspicuous by evolving subclones with less immunogenicity. We observed that smaller clonal mutation clusters with higher immunogenicity in tumor were more likely to involve in clonal evolution. Based on identified neoantigen profiles, we also discovered series of neoantigenic hotspot genes, which could serve as potential actionable targets in future.Conclusions: Our results revealed the landscape of HCC neoantigens and discovered two clinically relevant subgroups with distinct neoantigen expression patterns, suggesting the neoantigen expression should be fully considered in future immunotherapeutic interventions.展开更多
AIM:To investigate the histological origin of pseudomyxoma peritonei(PMP)in Chinese women.METHODS:The clinical and pathological data were reviewed for 35 women with PMP,and specimens of the peritoneal,appendiceal and ...AIM:To investigate the histological origin of pseudomyxoma peritonei(PMP)in Chinese women.METHODS:The clinical and pathological data were reviewed for 35 women with PMP,and specimens of the peritoneal,appendiceal and ovarian lesions of each patient were examined using the PV-6000 immunohistochemistry method.Antibodies included cytokeratin(CK)7,CK20,mucin(MUC)-1,MUC-2,carbohydrate antigen(CA)-125,estrogen receptor(ER),and progesterone receptor(PR).RESULTS:Abundant colloidal mucinous tumors were observed in the peritoneum in all 35 cases.Thirty-one patients had a history of appendectomy,28 of whom had mucinous lesions.There was one patient with appendicitis,one whose appendix showed no apparent pathological changes,and one with unknown surgical pathology.Ovarian mucinous tumors were found in 24 patients.The tumors were bilateral in 13 patients,on the right-side in nine,and on the left side in two.Twenty patients had combined appendiceal and ovarian lesions;16 of whom had undergone initial surgery for appendiceal lesions.Four patients had undergone initial surgery for ovarian lesions,and relapse occurred in these patients at 1,11,32 and 85 mo after initial surgery.Appendi-ceal mucinous tumors were found in each of these four patients.Thirty-three of the 35 patients showed peritoneal lesions that were positive for CK20 and MUC-2,but negative for CK7,MUC-1,CA125,ER and PR.The expression patterns in the appendix and the ovary were similar to those of the peritoneal lesions.In one of the remaining two cases,CK20,CK7 and MUC-2 were positive,and MUC-1,CA125,ER and PR were negative.The ovaries were not resected.The appendix of one patient was removed at another hospital,and no specimen was evaluated.In the other case,the appendix appeared to be normal during surgery,and was not resected.Peritoneal and ovarian lesions were negative for CK20,MUC-2,CK7,MUC-1,CA125,ER and PR.CONCLUSION:Most PMP originated from the appendix.Among women with PMP,the ovarian tumors were implanted rather than primary.For patients with PMP,appendectomy should be performed routinely.The ovaries,especially the right ovaries should be explored.展开更多
The applied value of serum hepcidin in differential diagnosis of infection fevers versus tumor fevers was explored.A total of 432 fever patients were selected according to the domestic fever of unknown origin(FUO) d...The applied value of serum hepcidin in differential diagnosis of infection fevers versus tumor fevers was explored.A total of 432 fever patients were selected according to the domestic fever of unknown origin(FUO) diagnostic criteria from our hospital between June 2010 and November 2013.Venous blood samples were taken on the day 1,5,10 after admission.The infection group(98 cases) and the tumor group(50 cases) were set up based on the clinical and laboratory findings.ELISA was used to determine the serum hepcidin and IL-6 levels.SPSS 13.0 was used for statistical analysis.Hepcidin showed obvious descending trend on the 10 th day in both the bacterial infection group(66 cases) and the virus infection group(32 cases),and the descending trend was similar to that of inflammatory indexes such as procalcitonin(PCT),hypersensitive C-reactive protein(h-CRP),erythrocyte sedimentation rate(ESR),white blood cell(WBC),and ferritin.Serum hepcidin showed no obvious differences in the tumor group on the day 1,5,10 after admission.In the infection groups,serum hepcidin was positively correlated with IL-6(r=0.687,P=0.000) and CRP(r=0.487,P=0.026),but had a poor correlation with blood sedimentation,ferritin,PCT and WBC(P〉0.05).Monitoring dynamic changes of hepcidin and related inflammatory factors in patients with fever is expected to be used for clinical identification of infection fever and tumor fever.展开更多
Brain tumors are the leading cause of cancer death in children,with ependymoma being the third most common and posing a significant clinical burden.Its mechanism of pathogenesis,reliable prognostic indicators,and effe...Brain tumors are the leading cause of cancer death in children,with ependymoma being the third most common and posing a significant clinical burden.Its mechanism of pathogenesis,reliable prognostic indicators,and effective treatments other than surgical resection have all remained elusive.Until recently,ependymoma research was hindered by the small number of tumors available for study,low resolution of cytogenetic techniques,and lack of cell lines and animal models.Ependymoma heterogeneity,which manifests as variations in tumor location,patient age,histological grade,and clinical behavior,together with the observation of a balanced genomic profile in up to 50% of cases,presents additional challenges in understanding the development and progression of this disease.Despite these difficulties,we have made significant headway in the past decade in identifying the genetic alterations and pathways involved in ependymoma tumorigenesis through collaborative efforts and the application of microarray-based genetic(copy number) and transcriptome profiling platforms.Genetic characterization of ependymoma unraveled distinct mRNA-defined subclasses and led to the identification of radial glial cells as its cell type of origin.This review summarizes our current knowledge in the molecular genetics of ependymoma and proposes future research directions necessary to further advance this field.展开更多
Hepatocellular carcinoma (HCC) is a kind of malignancy with high potential of metastasis and multicentric occurrence. The treatment of recurrent hepatocellular carcinoma (RHCC) and multinodular hepatocellular carcinom...Hepatocellular carcinoma (HCC) is a kind of malignancy with high potential of metastasis and multicentric occurrence. The treatment of recurrent hepatocellular carcinoma (RHCC) and multinodular hepatocellular carcinoma (MHCC) is always a nodus because of the diverse clonal origin of RHCC/MHCC. Theoretically, the RHCC/MHCC can originate from intrahepatic metastasis (IM type) or multicentric occurrence (MO type). Our previous study proposed that there are at least 6 subtypes of clonal origin patterns in RHCC. RHCC and MHCC with different clonal origins have variant biological behaviors, clinical prognosis as well as treatment strategy. Generally speaking, patients with IM type HCC have a poorer prognosis compared with those with MO type HCC. Therefore, it is essential to emphasize the distribution of the clonal origin in HCC in order to determine the choice of clinical treatment. Undoubtedly, the detection of clonal origin pattern will become a promising breakthrough in the molecular pathological diagnosis of HCC. We should attach more attention to the establishment of a standardized molecular pathological clonal origin detection method and a new stratification of clinical treatment choice for RHCC/MHCC in future.展开更多
基金Supported by a grant from the National Natural Science Founda-tion of China(no.82200319).
文摘Clonal hematopoiesis(CH)is a clonally expanded population of hematopoietic stem cells carrying somatic mutations that differentiate through multilineage hematopoiesis to form terminally differentiated mature hematopoietic cells carrying markers of the clonal mutation.Genes integral to critical cellular processes such as epigenetic regulation,DNA damage response,and inflammation frequently carry these mutations.Clonal hematopoiesis becomes increasingly prevalent with age and is associated with an increased risk of hematological tumors and some nonhematological conditions.Recent insights have revealed that the mutations driving CH are not only implicated in hematologic neoplasms but also possess the potential to influence cardiovascular pathogenesis.Here,we reviewed up-to-date findings about the roles of CH in cardiovascular diseases and tumors and explored the clinical significance of CH,as well as look forward to future related studies,so as to provide valuable references for future research and clinical practice.
文摘This review is part two of three, which will present an update on the classification of gastrointestinal submucosal tumors. Part one treats of the diagnosis and part three of the therapeutic methods regarding gastrointestinal submucosal tumors. In the past there has been some confusion as to the classification of gastrointestinal submucosal tumors. Changes in classifications have emerged due to recent advances in mainly immunohistochemistry and electron microscopy. The aim of this paper is to update the reader on the current classification. Literature searches were performed to find information related to classification of gastrointestinal submucosal tumors. Based on these searches the twelve most frequent submucosal tumor types were chosen for description of their classification. The factors that indicate whether tumors are benign or malignant are mainly size and number of mitotic counts. Gastrointestinal stromal tumors are defined mainly by their CD117 positivity. In the future, there should be no more confusion between gastrointestinal stromal tumors and other types of submucosal tumors.2007 The WJG Press. All rights reserved.
基金supported by the grants from the National Natural Science Foundation of China(Nos.81072026 and 81272662)the Science Fund for Creative Research Groups of China(No.81221061)the Key Project of Science and Technology Committee of Shanghai(No.10411951000)
文摘Background:Combined hepatocellular and cholangiocarcinoma(CHC) is a unique subtype of liver cancer comprising both hepatocellular carcinoma(HCC) and intrahepatic cholangiocarcinoma(ICC);however,its cellular origin remains unclear.The purpose of this study was to investigate the clinicopathologic features and the clonal relationship between HCC and ICC in 34 patients with CHC.Methods:The clinicopathologic features and prognosis of the 34 CHC patients were compared with those of 29 patients with separated HCC and ICC(5HC).Loss of heterozygosity(LOH) at 10 highly polymorphic microsatellite markers was detected in 16 CHC and 10 SHC tissues for determination of the clonal origin of CHC.Expression of hepatocyte markers[hepatocyte paraffin 1(Hep Par 1) and glypican 3(GPC3)]and cholangiocyte markers[cytokeratin(CK)7 and 19]in tumor tissues was examined by immuno histochemical analysis.Results:In the 16 CHC specimens,the difference in LOH patterns between HCC and ICC was less than 30%,suggesting the same clonal origin of HCC and ICC.Consistent with this finding,immunohistochemical analysis revealed that hepatocyte markers(Hep Par 1 and GPC3) and cholangiocyte markers(CK7 and CK19) were simultaneously expressed in both the HCC and ICC components in 52.9%of CHC specimens,suggesting that the two components shared a similar phenotype with hepatic progenitor cells(HPCs).On the contrary,in all 10 SHC cases,the difference in LOH patterns between the HCC and ICC components was greater than 30%,suggesting different clonal origins of HCC and ICC.Overall survival and disease-free survival were shorter for patients with CHC than for patients with SHC(P < 0.05).Conclusions:Our results suggest that the HCC and ICC components of CHC may originate from the same clone,having the potential for dual-directional differentiation similar to HPCs.CHC tended to exhibit the biological behaviors of both HCC and ICC,which may enhance the infiltrative capacity of tumor cells,leading to poor clinical outcomes for patients with CHC.
文摘AIM To observe the natural course of 1-3 cm gastric submucosal tumors originating from the muscularis propria(SMTMPs).METHODS By reviewing the computerized medical records over a period of 14 years(2000-2013), patients with 1-3 cm gastric SMTMPs who underwent at least two endoscopic ultrasound(EUS) examinations were enrolled. Tumor progression was defined as a ≥ 1.2 times enlargement in tumor diameter observed during EUS surveillance. All patients were divided into stationary and progressive subgroups and further analyzed. We also reviewed the patients in the progressive subgroup again in 2016.RESULTS A total of 88 patients were studied, including 25 in the progressive subgroup. The mean time of EUS surveillance was 24.6 mo in the stationary subgroup and 30.7 mo in the progressive subgroup. Risk factors for tumor progression included larger tumor size and irregular border. Initial tumor size > 14.0 mm may be considered a cut-off size for predicting tumor progression. Seventeen patients underwent surgery, of whom 13 had gastrointestinal stromal tumors(GISTs) and 4 had leiomyomas. Tumor progression was found only in patients with GISTs. All of the tumors exhibited benign behaviors without metastasis until 2016.CONCLUSION Most 1-3 cm gastric SMTMPs(71.6%) are indolent. Tumor progression was found only in GISTs, and it is a good predictor for differentiating GISTs from leiomyomas. Predictors of tumor progression include larger tumor size(> 14.0 mm) and irregular border.
基金supported by grants of China National Funds for Distinguished Young Scientists (Grant No. 81425019)National Natural Science Foundation of China (Grant No. 81672899)+2 种基金the State Key Program of National Natural Science Foundation of China (Grant No. 81730076)Shanghai Science and Technology Committee Program (Grant No. 18XD1405300)Specially-Appointed Professor Fund of Shanghai (Grant No. GZ2015009)
文摘Objective: Multiple mechanisms underlying the development of portal vein tumor thrombus(PVTT) in hepatocellular carcinoma(HCC) have been reported recently. However, the origins of PVTT remain unknown. Increasing multi-omics data on PVTTs in HCCs have made it possible to investigate whether PVTTs originate from the corresponding primary tumors(Ts).Methods: The clonal relationship between PVTTs and their corresponding primary Ts was investigated using datasets deposited in public databases. One DNA copy number variations dataset and three gene expression datasets were downloaded for the analyses.Clonality analysis was performed to investigate the clonal relationship between PVTTs and Ts from an individual patient.Differential gene expression analysis was applied to investigate the gene expression profiles of PVTTs and Ts.Results: One out of 19 PVTTs had no clonal relationship with its corresponding T, whereas the others did. The PVTTs with independent clonal origin showed different gene expression and enrichment in biological processes from the primary Ts. Based on the unique gene expression profiles, a gene signature including 24 genes was used to identify pairs of PVTTs and primary Ts without any clonal relationship. Validation in three datasets showed that these types of pairs of PVTTs and Ts can be identified by the 24-gene signature.Conclusions: Our findings show a direct evidence for PVTT origin and consolidate the heterogeneity of PVTTs observed in clinic.The results suggest that PVTT investigation at a molecular level is clinically necessary for diagnosis and treatment.
基金Supported by the Korea Science and Engineering Foundation through the MRCCMT at Dong-A University
文摘Collision tumors are thought to arise from the accidental meeting and interpenetration of two independent tumors. We report here a highly unusual case of a 61-year old man who had a unique tumor that was composed of a metastatic adenocarcinoma from the stomach to the rectum, which harbored a collision tumor of primary rectal adenocarcinoma. The clonalities of the two histologically distinct lesions of the rectal mass were confirmed by immunohistochemical and molecular analysis. Although histologic examination is the cornerstone in pathology, immunohistochemical and molecular analysis can provide evidence regarding whether tumors originate from the same clone or different clones. To the best of our knowledge, this is the fi rst reported case of such an occurrence.
文摘Objective:The high post-operative recurrence of hepatocellular carcinoma(RHCC)and multinodular hepatocellular carcinoma(MHCC)seriously limit the surgical efficacy of HCC.Theoretically,RHCC/MHCC arise from either residual tumor cells or novel clone-derived tumor cells which have a great impact on designing personalized therapies and the evaluation of clinical long-term outcome.
基金supported by the National Science and Technology Major Project of China (No. 2018ZX 10302205)the Scientific Foundation of Fujian Province (No. 2018J01145, No. 2020J011171)+1 种基金the Scientific Foundation of Fujian Health and family planning Department (No. 2019-ZQN-87)the Joint Funds for the Innovation of Science and Technology of Fujian Province (No. 2018Y9121)。
文摘Objective: Neoantigens derived from tumor-specific genomic alterations have demonstrated great potential for immunotherapeutic interventions in cancers. However, the comprehensive profile of hepatocellular carcinoma(HCC) neoantigens and their complex interplay with immune microenvironment and tumor evolution have not been fully addressed.Methods: Here we integrated whole exome sequencing data, transcriptome sequencing data and clinical information of 72 primary HCC patients to characterize the HCC neoantigen profile, and systematically explored its interactions with tumor clonal evolution, driver mutations and immune microenvironments.Results: We observed that higher somatic mutation/neoantigen load was associated with better clinical outcomes and HCC patients could be further divided into two subgroups with distinct prognosis based on their neoantigen expression patterns. HCC subgroup with neoantigen expression probability high(NEP-H) showed more aggressive pathologic features including increased incidence of tumor thrombus(P=0.038), higher recurrence rate(P=0.029),more inclined to lack tumor capsule(P=0.026) and with more microsatellite instability sites(P=0.006). In addition,NEP-H subgroup was also characterized by higher chance to be involved in tumor clonal evolution [odds ratio(OR)=46.7, P<0.001]. Gene set enrichment analysis revealed that upregulation of MYC and its targets could suppress immune responses, leading to elevated neoantigen expression proportion in tumor cells. Furthermore, we discovered an immune escape mechanism that tumors could become more inconspicuous by evolving subclones with less immunogenicity. We observed that smaller clonal mutation clusters with higher immunogenicity in tumor were more likely to involve in clonal evolution. Based on identified neoantigen profiles, we also discovered series of neoantigenic hotspot genes, which could serve as potential actionable targets in future.Conclusions: Our results revealed the landscape of HCC neoantigens and discovered two clinically relevant subgroups with distinct neoantigen expression patterns, suggesting the neoantigen expression should be fully considered in future immunotherapeutic interventions.
文摘AIM:To investigate the histological origin of pseudomyxoma peritonei(PMP)in Chinese women.METHODS:The clinical and pathological data were reviewed for 35 women with PMP,and specimens of the peritoneal,appendiceal and ovarian lesions of each patient were examined using the PV-6000 immunohistochemistry method.Antibodies included cytokeratin(CK)7,CK20,mucin(MUC)-1,MUC-2,carbohydrate antigen(CA)-125,estrogen receptor(ER),and progesterone receptor(PR).RESULTS:Abundant colloidal mucinous tumors were observed in the peritoneum in all 35 cases.Thirty-one patients had a history of appendectomy,28 of whom had mucinous lesions.There was one patient with appendicitis,one whose appendix showed no apparent pathological changes,and one with unknown surgical pathology.Ovarian mucinous tumors were found in 24 patients.The tumors were bilateral in 13 patients,on the right-side in nine,and on the left side in two.Twenty patients had combined appendiceal and ovarian lesions;16 of whom had undergone initial surgery for appendiceal lesions.Four patients had undergone initial surgery for ovarian lesions,and relapse occurred in these patients at 1,11,32 and 85 mo after initial surgery.Appendi-ceal mucinous tumors were found in each of these four patients.Thirty-three of the 35 patients showed peritoneal lesions that were positive for CK20 and MUC-2,but negative for CK7,MUC-1,CA125,ER and PR.The expression patterns in the appendix and the ovary were similar to those of the peritoneal lesions.In one of the remaining two cases,CK20,CK7 and MUC-2 were positive,and MUC-1,CA125,ER and PR were negative.The ovaries were not resected.The appendix of one patient was removed at another hospital,and no specimen was evaluated.In the other case,the appendix appeared to be normal during surgery,and was not resected.Peritoneal and ovarian lesions were negative for CK20,MUC-2,CK7,MUC-1,CA125,ER and PR.CONCLUSION:Most PMP originated from the appendix.Among women with PMP,the ovarian tumors were implanted rather than primary.For patients with PMP,appendectomy should be performed routinely.The ovaries,especially the right ovaries should be explored.
文摘The applied value of serum hepcidin in differential diagnosis of infection fevers versus tumor fevers was explored.A total of 432 fever patients were selected according to the domestic fever of unknown origin(FUO) diagnostic criteria from our hospital between June 2010 and November 2013.Venous blood samples were taken on the day 1,5,10 after admission.The infection group(98 cases) and the tumor group(50 cases) were set up based on the clinical and laboratory findings.ELISA was used to determine the serum hepcidin and IL-6 levels.SPSS 13.0 was used for statistical analysis.Hepcidin showed obvious descending trend on the 10 th day in both the bacterial infection group(66 cases) and the virus infection group(32 cases),and the descending trend was similar to that of inflammatory indexes such as procalcitonin(PCT),hypersensitive C-reactive protein(h-CRP),erythrocyte sedimentation rate(ESR),white blood cell(WBC),and ferritin.Serum hepcidin showed no obvious differences in the tumor group on the day 1,5,10 after admission.In the infection groups,serum hepcidin was positively correlated with IL-6(r=0.687,P=0.000) and CRP(r=0.487,P=0.026),but had a poor correlation with blood sedimentation,ferritin,PCT and WBC(P〉0.05).Monitoring dynamic changes of hepcidin and related inflammatory factors in patients with fever is expected to be used for clinical identification of infection fever and tumor fever.
文摘Brain tumors are the leading cause of cancer death in children,with ependymoma being the third most common and posing a significant clinical burden.Its mechanism of pathogenesis,reliable prognostic indicators,and effective treatments other than surgical resection have all remained elusive.Until recently,ependymoma research was hindered by the small number of tumors available for study,low resolution of cytogenetic techniques,and lack of cell lines and animal models.Ependymoma heterogeneity,which manifests as variations in tumor location,patient age,histological grade,and clinical behavior,together with the observation of a balanced genomic profile in up to 50% of cases,presents additional challenges in understanding the development and progression of this disease.Despite these difficulties,we have made significant headway in the past decade in identifying the genetic alterations and pathways involved in ependymoma tumorigenesis through collaborative efforts and the application of microarray-based genetic(copy number) and transcriptome profiling platforms.Genetic characterization of ependymoma unraveled distinct mRNA-defined subclasses and led to the identification of radial glial cells as its cell type of origin.This review summarizes our current knowledge in the molecular genetics of ependymoma and proposes future research directions necessary to further advance this field.
文摘Hepatocellular carcinoma (HCC) is a kind of malignancy with high potential of metastasis and multicentric occurrence. The treatment of recurrent hepatocellular carcinoma (RHCC) and multinodular hepatocellular carcinoma (MHCC) is always a nodus because of the diverse clonal origin of RHCC/MHCC. Theoretically, the RHCC/MHCC can originate from intrahepatic metastasis (IM type) or multicentric occurrence (MO type). Our previous study proposed that there are at least 6 subtypes of clonal origin patterns in RHCC. RHCC and MHCC with different clonal origins have variant biological behaviors, clinical prognosis as well as treatment strategy. Generally speaking, patients with IM type HCC have a poorer prognosis compared with those with MO type HCC. Therefore, it is essential to emphasize the distribution of the clonal origin in HCC in order to determine the choice of clinical treatment. Undoubtedly, the detection of clonal origin pattern will become a promising breakthrough in the molecular pathological diagnosis of HCC. We should attach more attention to the establishment of a standardized molecular pathological clonal origin detection method and a new stratification of clinical treatment choice for RHCC/MHCC in future.