BACKGROUND As one of the subsets of CD8+T cells,Tc17 cells have recently been identified and are characterized by the secretion of interleukin(IL)-17,which is related to inflammatory diseases.AIM To assess the status ...BACKGROUND As one of the subsets of CD8+T cells,Tc17 cells have recently been identified and are characterized by the secretion of interleukin(IL)-17,which is related to inflammatory diseases.AIM To assess the status of Tc17 cells in cervical cancer and investigate the biological function of Tc17 cells in cervical cancer development.METHODS Flow cytometry assay,immunohistochemistry,and immunofluorescence were performed to detect the levels and phenotype of Tc17 cells in blood and tumor samples from patients with cervical cancer.Prior to cell suspension culture,ELISA was carried out to measure the production of IL-6,IL-1β,IL-23,CXCL12,and IL-17 in tumor tissue supernatant and co-cultured supernatant of patients with cervical cancer.In addition,multivariate analysis was performed to identify factors associated with overall survival using the Cox proportional hazards model.RESULTS Compared with normal tissues,Tc17 cells specifically accumulated in tumor tissues of cervical cancer patients.Cancer cells produced a greater amount of IL-6,IL-1β,and IL-23,which in turn promoted Tc17 cell polarization.Unlike the traditional cytotoxic CD8^+T cells,Tc17 cells secreted IL-17,which subsequently promoted CXCL12 expression in tumor cells,eventually enhancing the proliferation and migration of tumor cells.Thus,the ratio of tumor-infiltrating Tc17 cells was highly correlated with poor clinical outcome in patients with cervical cancer.CONCLUSION Our data identified the oncogenic role of Tc17 cells in the development of cervical cancer.We propose that the ratio of Tc17 cells may be a useful index in the prognosis of patients with cervical cancer.展开更多
Short-term stress positively affects homeostasis recovery;however,long-term stress leads to various diseases.Accumulating evidence shows that cancer processes are not only related to genetics and environment but also ...Short-term stress positively affects homeostasis recovery;however,long-term stress leads to various diseases.Accumulating evidence shows that cancer processes are not only related to genetics and environment but also to chronic stress.For patients with cancer,the disease process induces prolonged psychological and physical stress,including fear and pain,which makes chronic stress common in patients.Chronic stress,in turn,regulates different components of the primary tumor and tumor microenvironment through a wide variety of stress mediators.Furthermore,studies indicate that chronic stress increases tumor burden and mortality in patients with different types of cancer,while the management of chronic stress can alleviate disease burden and extend patient survival.Therefore,a deeper understanding of the role and mechanism of chronic stress in cancer is necessary for developing new strategies for cancer treatment beyond traditional treatment approaches.Herein,we explored the different sources of chronic stress,the molecular mechanisms through which chronic stress affects cancer development and progression,and the stress mediators involved.We discussed the multiple impacts of chronic stress on cancer,as well as the currently available intervention strategies.We also highlighted the prospects and challenges of chronic stress management in the clinical treatment of cancer.展开更多
Although the type and etiology of cancers are different, pathways in glucose metabolism, pentose phosphate pathway(PPP) and glutamine metabolism have been reprogrammed in cancer cells to adapt to their rapid growth an...Although the type and etiology of cancers are different, pathways in glucose metabolism, pentose phosphate pathway(PPP) and glutamine metabolism have been reprogrammed in cancer cells to adapt to their rapid growth and proliferation. Recent research has also shown that multiple lipid metabolic pathways are altered in cancer cells.Here, we provide a brief review for the role of fatty acid metabolism in cancer development with a special focus on fatty acid uptake and de novo synthesis, triglycerides synthesis, storage and degradation. Reprogramming in fatty acid metabolism plays important roles in providing energy,macromolecules for membrane synthesis and lipid signals during cancer development. Understanding the mechanism of deregulated lipid metabolic pathways in cancer cells would reveal novel therapeutic approaches to combat cancer.展开更多
Microrchidia CW-type zinc finger 2(MORC2)is a member of the MORC superfamily of nuclear proteins.Growing evidence has shown that MORC2 not only participates in gene transcription and chromatin remodeling but also play...Microrchidia CW-type zinc finger 2(MORC2)is a member of the MORC superfamily of nuclear proteins.Growing evidence has shown that MORC2 not only participates in gene transcription and chromatin remodeling but also plays a key in human disease and tumor development by regulating the expression of downstream oncogenes or tumor suppressors.The present review provides an updated overview of MORC2 in the aspect of cancer hallmark and therapeutic resistance and summarizes its upstream regulators and downstream target genes.This systematic review may provide a favorable theoretical basis for emerging players of MORC2 in tumor development and new insight into the potential clinical application of basic science discoveries in the future.展开更多
Human gastrointestinal tract harbours trillions of microbes to form the gut microbiota.Through interacting with host cells,gut microbes play critical roles in host physiology and function.On the other hand,an altered ...Human gastrointestinal tract harbours trillions of microbes to form the gut microbiota.Through interacting with host cells,gut microbes play critical roles in host physiology and function.On the other hand,an altered or dysbiotic microbiota is now well acknowledged for contributing to cancer development and progression.Since the last decade,immunotherapy has risen as a promising and novel means to fight against cancer.Meanwhile,accumulating studies have clearly revealed the close association of gut microbiota with immunotherapy efficacy,suggesting the feasibility of modulating microbiota to improve treatment responsiveness.In this review,we present the current evidence elucidating the interplay between gut microbiota and immune system in the development of several cancers including colorectal cancer,hepatocellular carcinoma and melanoma.We also discuss how the gut microbiota impacts immune checkpoint inhibitors,one of the most common approaches of immunotherapy,and explore approaches that aim to harness the gut microbiota to improve treatment efficacy.Overall,investigations on the relationship between microbiota and cancer immunotherapy can have important clinical significance,potentially leading to the development of more potent and effective cancer therapeutics in the near future.展开更多
In vitro 3D cancer spheroids (tumoroids) exhibit a drug resistance profile similar to that found in solid tumors. 3D spheroid culture methods recreate more physiologically relevant microenvironments for cells. Therefo...In vitro 3D cancer spheroids (tumoroids) exhibit a drug resistance profile similar to that found in solid tumors. 3D spheroid culture methods recreate more physiologically relevant microenvironments for cells. Therefore, these models are more appropriate for cancer drug screening. We have recently developed a protocol for MCF-7 cell spheroid culture, and used this method to test the effects of different types of drugs on this estrogen-dependent breast cancer cell spheroid. Our results demonstrated that MCF-7 cells can grow spheroid in medium using a low attachment plate. We managed to grow one spheroid in each well, and the spheroid can grow over a month, the size of the spheroid can grow over a hundred times in volume. Our targeted drug experimental results suggest that estrogen sulfotransferase, steroid sulfatase, and G protein-coupled estrogen receptor may play critical roles in MCF-7 cell spheroid growth, while estrogen receptors α and β may not play an essential role in MCF-7 spheroid growth. Organoids are the miniatures of in vivo tissues and reiterate the in vivo microenvironment of a specific organ, best fit for the in vitro studies of diseases and drug development. Tumoroid, developed from cancer cell lines or patients’ tumor tissue, is the best in vitro model of in vivo tumors. 3D spheroid technology will be the best future method for drug development of cancers and other diseases. Our reported method can be developed clinically to develop personalized drugs when the patient’s tumor tissues are used to develop a spheroid culture for drug screening.展开更多
Exercise can enhance motivation to change lifestyle behaviors,improve aerobic fitness,improve physical function,control fatigue,and enhance quality of life.Studies have demonstrated the benefits to be gained from phys...Exercise can enhance motivation to change lifestyle behaviors,improve aerobic fitness,improve physical function,control fatigue,and enhance quality of life.Studies have demonstrated the benefits to be gained from physical exercise,highlighting the importance of popularizing the concept of physical exercise for individuals and making professional exercise-treatment programs available to patients with cancer.However,the correlation between physical exercise and carcinogenesis is easily overlooked,and exercise interventions are not routinely provided to patients with cancer,especially those with advanced cancer.In this article,we present a literature review of the effects of exercise on cancer development and progression and give recent evidence for the type of exercise best suited for different types of cancer and in different disease stages.Moreover,the molecular mechanisms about regulating metabolism and systemic immune function in cancer are summarized and discussed.In conclusion,physical exercise should be considered as an important intervention for preventing and treating cancer and its complications.展开更多
The microbiota impact on human diseases is well-known,and a growing body of literature is providing evidence about the complex interplay between microbiotaimmune system-human physiology/pathology,including cancers.Tog...The microbiota impact on human diseases is well-known,and a growing body of literature is providing evidence about the complex interplay between microbiotaimmune system-human physiology/pathology,including cancers.Together with the defined risk factors(e.g.,smoke habits,diet,diabetes,and obesity),the oral,gut,biliary,and intrapancreatic microbiota contribute to pancreatic cancer development through different pathways including the interaction with the immune system.Unfortunately,a great majority of the pancreatic cancer patients received a diagnosis in advanced stages not amenable to be radically treated and potentially cured.Given the poor pancreatic cancer prognosis,complete knowledge of these complicated relationships could help researchers better understand the disease pathogenesis and thus provide early potential noninvasive biomarkers,new therapeutic targets,and tools for risk stratification that might result in greater therapeutic possibilities and eventually in a better and longer patient survival.展开更多
AIM:To describe the clinical and epidemiologic profiles of the disease and to compare the findings with those generated from the previous hospital-based studies.METHODS:The Gharbiah cancer registry is the only populat...AIM:To describe the clinical and epidemiologic profiles of the disease and to compare the findings with those generated from the previous hospital-based studies.METHODS:The Gharbiah cancer registry is the only population-based cancer registry in Egypt since 1998.We analyzed the data of all colorectal cancer patients included in the registry for the period of 1999-2007.All medical records of the 1364 patients diagnosed in Gharbiah during the study period were retrieved and the following information abstracted:age,residence,diagnosis date,grade,stage,topology,clinical characteristics,and histology variables.Egyptian census data for 1996 and 2006 were used to provide the general population's statistics on age,sex,residence and other related demographic factors.In addition to age-and sex-specific incidence rate analyses,we analyze the data to explore the incidence distribution by rural-urban differences among the 8 districts of the province.We also compared the incidence rates of Gharbiah to the rates of the Surveillance Epidemiology and End Results(SEER) data of the United States.RESULTS:Over the 9 year-period,1364 colorectal cancer cases were included.The disease incidence under age 40 years was relatively high(1.3/10 5) while the incidence in the age groups 40 and over was very low(12.0/10 5,19.4/10 5 and 21.2/10 5 in the age groups 40-59 years,60-69 years and > 70 years,respectively).The vast majority of tumors(97.2%) had no polyps and 37.2% of the patients presented with primary lesions in the rectum.Colorectal cancer was more common in patients from urban(55%) than rural(45%) areas.Regional differences in colon and rectal cancer incidence in the 8 districts of the study province may reflect different etiologic patterns in this population.The registry data of Egypt shows a slightly higher incidence of colorectal cancer than the United States in subjects under age 40 years.The results also shows significantly lower incidence of colorectal cancer in subjects over age 40 years compared to the same age group in the United States SEER.CONCLUSION:Low rate of polyps,low incidence in older subjects,and high rate of rectal cancer in Egypt.Future studies should explore clinical and molecular disease patterns.展开更多
Ubiquitination,a multifaceted post-translational modification,regulates protein function,degradation,and gene expression.The pivotal role of ubiquitination in the pathogenesis and progression of cancer,including color...Ubiquitination,a multifaceted post-translational modification,regulates protein function,degradation,and gene expression.The pivotal role of ubiquitination in the pathogenesis and progression of cancer,including colorectal,breast,and liver cancer,is well-established.Osteosarcoma,an aggressive bone tumor predominantly affecting adolescents,also exhibits dysregulation of the ubiquitination system,encompassing both ubiquitination and deubiquitination processes.This dysregulation is now recognized as a key driver of osteosarcoma development,progression,and chemoresistance.This review highlights recent progress in elucidating how ubiquitination modulates tumor behavior across signaling pathways.We then focus on the mechanisms by which ubiquitination influences osteosarcoma cell function.Finally,we discuss the potential for targeting the ubiquitin-proteasome system in osteosarcoma therapy.By unraveling the impact of ubiquitination on osteosarcoma cell physiology,we aim to facilitate the development of novel strategies for prognosis,staging,treatment,and overcoming chemoresistance.展开更多
文摘BACKGROUND As one of the subsets of CD8+T cells,Tc17 cells have recently been identified and are characterized by the secretion of interleukin(IL)-17,which is related to inflammatory diseases.AIM To assess the status of Tc17 cells in cervical cancer and investigate the biological function of Tc17 cells in cervical cancer development.METHODS Flow cytometry assay,immunohistochemistry,and immunofluorescence were performed to detect the levels and phenotype of Tc17 cells in blood and tumor samples from patients with cervical cancer.Prior to cell suspension culture,ELISA was carried out to measure the production of IL-6,IL-1β,IL-23,CXCL12,and IL-17 in tumor tissue supernatant and co-cultured supernatant of patients with cervical cancer.In addition,multivariate analysis was performed to identify factors associated with overall survival using the Cox proportional hazards model.RESULTS Compared with normal tissues,Tc17 cells specifically accumulated in tumor tissues of cervical cancer patients.Cancer cells produced a greater amount of IL-6,IL-1β,and IL-23,which in turn promoted Tc17 cell polarization.Unlike the traditional cytotoxic CD8^+T cells,Tc17 cells secreted IL-17,which subsequently promoted CXCL12 expression in tumor cells,eventually enhancing the proliferation and migration of tumor cells.Thus,the ratio of tumor-infiltrating Tc17 cells was highly correlated with poor clinical outcome in patients with cervical cancer.CONCLUSION Our data identified the oncogenic role of Tc17 cells in the development of cervical cancer.We propose that the ratio of Tc17 cells may be a useful index in the prognosis of patients with cervical cancer.
基金supported by the National Natural Science Fundation of China(32125016,32525002,32025011,W2411011,T2321005,and U24A20371)programs from the Ministry of Science and Technology of China(2024YFC2707400,2021YFA1101000,2022YFA1105200,and 2023YFA1800200)+6 种基金a Key R&D Program of Zhejiang Province(2024C03142)a project funded by Basic Research Program of Jiangsu(BK20250359)Jiangsu Funding Program for Excellent Postdoctoral Talent,the China Postdoctoral Science Foundation(2025M772706)the Suzhou Medical College Basic Frontier Innovation Cross Project(YXY2303027)the Suzhou Medical College-Qilu Medical Research Program of Soochow University(24QL101301)the Joint Project of Pinnacle Disciplinary Group,the Second Affiliated Hospital of Chongqing Medical,Principal Investigator Foundation of Tianfu Jincheng Laboratory(TFJCPI20250022)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions,and the Postdoctoral Research Fund of The First Affiliated Hospital of Soochow University(09020320250001).
文摘Short-term stress positively affects homeostasis recovery;however,long-term stress leads to various diseases.Accumulating evidence shows that cancer processes are not only related to genetics and environment but also to chronic stress.For patients with cancer,the disease process induces prolonged psychological and physical stress,including fear and pain,which makes chronic stress common in patients.Chronic stress,in turn,regulates different components of the primary tumor and tumor microenvironment through a wide variety of stress mediators.Furthermore,studies indicate that chronic stress increases tumor burden and mortality in patients with different types of cancer,while the management of chronic stress can alleviate disease burden and extend patient survival.Therefore,a deeper understanding of the role and mechanism of chronic stress in cancer is necessary for developing new strategies for cancer treatment beyond traditional treatment approaches.Herein,we explored the different sources of chronic stress,the molecular mechanisms through which chronic stress affects cancer development and progression,and the stress mediators involved.We discussed the multiple impacts of chronic stress on cancer,as well as the currently available intervention strategies.We also highlighted the prospects and challenges of chronic stress management in the clinical treatment of cancer.
基金supported by the National Basic Research Program(2013CB530602)the National Natural Science Foundation of China(31430040,31321003)
文摘Although the type and etiology of cancers are different, pathways in glucose metabolism, pentose phosphate pathway(PPP) and glutamine metabolism have been reprogrammed in cancer cells to adapt to their rapid growth and proliferation. Recent research has also shown that multiple lipid metabolic pathways are altered in cancer cells.Here, we provide a brief review for the role of fatty acid metabolism in cancer development with a special focus on fatty acid uptake and de novo synthesis, triglycerides synthesis, storage and degradation. Reprogramming in fatty acid metabolism plays important roles in providing energy,macromolecules for membrane synthesis and lipid signals during cancer development. Understanding the mechanism of deregulated lipid metabolic pathways in cancer cells would reveal novel therapeutic approaches to combat cancer.
基金financially supported in part by grants from the National Natural Science Foundation of China(No.81572611 and 81828009)the Foundation Committee of Basic Research of Liaoning Province,China(No.LJKMZ20221205)the Application Foundation Plan Project of Liaoning Provincial Department of Science and Technology(China)(No.2023JH2/101300012).
文摘Microrchidia CW-type zinc finger 2(MORC2)is a member of the MORC superfamily of nuclear proteins.Growing evidence has shown that MORC2 not only participates in gene transcription and chromatin remodeling but also plays a key in human disease and tumor development by regulating the expression of downstream oncogenes or tumor suppressors.The present review provides an updated overview of MORC2 in the aspect of cancer hallmark and therapeutic resistance and summarizes its upstream regulators and downstream target genes.This systematic review may provide a favorable theoretical basis for emerging players of MORC2 in tumor development and new insight into the potential clinical application of basic science discoveries in the future.
基金supported by the National Key R&D Program of China(2020YFA0509200/2020YFA0509203)Shenzhen-Hong Kong-Macao Science and Technology Program(Category C),Shenzhen(SGDX20210823103535016)+1 种基金RGC-GRF(14117422,14117123)the National Natural Science Foundation of China(82103355,82272619 and 82222901).
文摘Human gastrointestinal tract harbours trillions of microbes to form the gut microbiota.Through interacting with host cells,gut microbes play critical roles in host physiology and function.On the other hand,an altered or dysbiotic microbiota is now well acknowledged for contributing to cancer development and progression.Since the last decade,immunotherapy has risen as a promising and novel means to fight against cancer.Meanwhile,accumulating studies have clearly revealed the close association of gut microbiota with immunotherapy efficacy,suggesting the feasibility of modulating microbiota to improve treatment responsiveness.In this review,we present the current evidence elucidating the interplay between gut microbiota and immune system in the development of several cancers including colorectal cancer,hepatocellular carcinoma and melanoma.We also discuss how the gut microbiota impacts immune checkpoint inhibitors,one of the most common approaches of immunotherapy,and explore approaches that aim to harness the gut microbiota to improve treatment efficacy.Overall,investigations on the relationship between microbiota and cancer immunotherapy can have important clinical significance,potentially leading to the development of more potent and effective cancer therapeutics in the near future.
文摘In vitro 3D cancer spheroids (tumoroids) exhibit a drug resistance profile similar to that found in solid tumors. 3D spheroid culture methods recreate more physiologically relevant microenvironments for cells. Therefore, these models are more appropriate for cancer drug screening. We have recently developed a protocol for MCF-7 cell spheroid culture, and used this method to test the effects of different types of drugs on this estrogen-dependent breast cancer cell spheroid. Our results demonstrated that MCF-7 cells can grow spheroid in medium using a low attachment plate. We managed to grow one spheroid in each well, and the spheroid can grow over a month, the size of the spheroid can grow over a hundred times in volume. Our targeted drug experimental results suggest that estrogen sulfotransferase, steroid sulfatase, and G protein-coupled estrogen receptor may play critical roles in MCF-7 cell spheroid growth, while estrogen receptors α and β may not play an essential role in MCF-7 spheroid growth. Organoids are the miniatures of in vivo tissues and reiterate the in vivo microenvironment of a specific organ, best fit for the in vitro studies of diseases and drug development. Tumoroid, developed from cancer cell lines or patients’ tumor tissue, is the best in vitro model of in vivo tumors. 3D spheroid technology will be the best future method for drug development of cancers and other diseases. Our reported method can be developed clinically to develop personalized drugs when the patient’s tumor tissues are used to develop a spheroid culture for drug screening.
文摘Exercise can enhance motivation to change lifestyle behaviors,improve aerobic fitness,improve physical function,control fatigue,and enhance quality of life.Studies have demonstrated the benefits to be gained from physical exercise,highlighting the importance of popularizing the concept of physical exercise for individuals and making professional exercise-treatment programs available to patients with cancer.However,the correlation between physical exercise and carcinogenesis is easily overlooked,and exercise interventions are not routinely provided to patients with cancer,especially those with advanced cancer.In this article,we present a literature review of the effects of exercise on cancer development and progression and give recent evidence for the type of exercise best suited for different types of cancer and in different disease stages.Moreover,the molecular mechanisms about regulating metabolism and systemic immune function in cancer are summarized and discussed.In conclusion,physical exercise should be considered as an important intervention for preventing and treating cancer and its complications.
文摘The microbiota impact on human diseases is well-known,and a growing body of literature is providing evidence about the complex interplay between microbiotaimmune system-human physiology/pathology,including cancers.Together with the defined risk factors(e.g.,smoke habits,diet,diabetes,and obesity),the oral,gut,biliary,and intrapancreatic microbiota contribute to pancreatic cancer development through different pathways including the interaction with the immune system.Unfortunately,a great majority of the pancreatic cancer patients received a diagnosis in advanced stages not amenable to be radically treated and potentially cured.Given the poor pancreatic cancer prognosis,complete knowledge of these complicated relationships could help researchers better understand the disease pathogenesis and thus provide early potential noninvasive biomarkers,new therapeutic targets,and tools for risk stratification that might result in greater therapeutic possibilities and eventually in a better and longer patient survival.
基金Supported by The National Cancer Institute Grant,No.R25CA112383 (to Veruttipong D and Gilbert SF)the University of Michigan Center for Global Health
文摘AIM:To describe the clinical and epidemiologic profiles of the disease and to compare the findings with those generated from the previous hospital-based studies.METHODS:The Gharbiah cancer registry is the only population-based cancer registry in Egypt since 1998.We analyzed the data of all colorectal cancer patients included in the registry for the period of 1999-2007.All medical records of the 1364 patients diagnosed in Gharbiah during the study period were retrieved and the following information abstracted:age,residence,diagnosis date,grade,stage,topology,clinical characteristics,and histology variables.Egyptian census data for 1996 and 2006 were used to provide the general population's statistics on age,sex,residence and other related demographic factors.In addition to age-and sex-specific incidence rate analyses,we analyze the data to explore the incidence distribution by rural-urban differences among the 8 districts of the province.We also compared the incidence rates of Gharbiah to the rates of the Surveillance Epidemiology and End Results(SEER) data of the United States.RESULTS:Over the 9 year-period,1364 colorectal cancer cases were included.The disease incidence under age 40 years was relatively high(1.3/10 5) while the incidence in the age groups 40 and over was very low(12.0/10 5,19.4/10 5 and 21.2/10 5 in the age groups 40-59 years,60-69 years and > 70 years,respectively).The vast majority of tumors(97.2%) had no polyps and 37.2% of the patients presented with primary lesions in the rectum.Colorectal cancer was more common in patients from urban(55%) than rural(45%) areas.Regional differences in colon and rectal cancer incidence in the 8 districts of the study province may reflect different etiologic patterns in this population.The registry data of Egypt shows a slightly higher incidence of colorectal cancer than the United States in subjects under age 40 years.The results also shows significantly lower incidence of colorectal cancer in subjects over age 40 years compared to the same age group in the United States SEER.CONCLUSION:Low rate of polyps,low incidence in older subjects,and high rate of rectal cancer in Egypt.Future studies should explore clinical and molecular disease patterns.
基金the Sichuan Provincial Central Leading Local Science and Technology Development Special Project(Grant No.2023ZYD0072)the National Natural Science Foundation of China(Grant No.82301785)the Guangdong Basic and Applied Basic Research Foundation(Grant No.2019A1515111078).
文摘Ubiquitination,a multifaceted post-translational modification,regulates protein function,degradation,and gene expression.The pivotal role of ubiquitination in the pathogenesis and progression of cancer,including colorectal,breast,and liver cancer,is well-established.Osteosarcoma,an aggressive bone tumor predominantly affecting adolescents,also exhibits dysregulation of the ubiquitination system,encompassing both ubiquitination and deubiquitination processes.This dysregulation is now recognized as a key driver of osteosarcoma development,progression,and chemoresistance.This review highlights recent progress in elucidating how ubiquitination modulates tumor behavior across signaling pathways.We then focus on the mechanisms by which ubiquitination influences osteosarcoma cell function.Finally,we discuss the potential for targeting the ubiquitin-proteasome system in osteosarcoma therapy.By unraveling the impact of ubiquitination on osteosarcoma cell physiology,we aim to facilitate the development of novel strategies for prognosis,staging,treatment,and overcoming chemoresistance.
