BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors of the digestive system worldwide,the prognosis of patients with advanced GC remains poor.AIM To evaluate the combined expression characteristics...BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors of the digestive system worldwide,the prognosis of patients with advanced GC remains poor.AIM To evaluate the combined expression characteristics of cancer stem cell markers CD24 and CD133 in GC pathological tissues,and to explore their association with patients’clinicopathological parameters and postoperative survival outcomes.METHODS A total of 304 GC patients who underwent surgical treatment in our hospital from January 2018 to January 2020 were retrospectively included.Immunohistochemistry was used to detect the protein expression of CD24 and CD133 in tumor tissues,adjacent tissues,and normal gastric mucosa tissues.Based on staining intensity and the proportion of positive cells,expression levels were classified into low and high expression,while clinicopathological parameters were recorded.χ2 test was used to evaluate the correlation between expression and categorical variables,Spearman rank correlation analysis was performed to assess the correlation between the expression intensities of the two markers,and multivariate regression models were applied to identify independent risk factors influencing co-expression.Kaplan-Meier survival curves and Log-rank test were used to compare survival differences among groups with different expression patterns.RESULTS Among the 304 patients,155 cases(50.99%)were CD24 positive,including 91 low-expression and 64 highexpression;133 cases(43.75%)were CD133 positive,including 81 low-expression and 52 high-expression.There were 74 cases(24.34%)with double positivity and 81 cases(26.64%)with double negativity.Compared with tumor tissues,the positive rates of CD24 and CD133 in normal gastric tissues and adjacent tissues were significantly lower(P<0.05).Univariate analysis showed that co-expression of CD24 and CD133 in GC tissues was significantly correlated with tumor size,Lauren classification,T stage,N stage,and vascular invasion(P<0.05),but not with patient age,gender,tumor site,World Health Organization histological classification,or M stage(P>0.05).Further multivariate regression analysis suggested that tumor size,T stage,N stage,and vascular invasion were independent risk factors promoting CD24 and CD133 double positivity.Spearman rank correlation analysis indicated a moderate positive correlation between their expression intensities(r=0.420,P<0.001).During follow-up,29 of 304 patients were lost(loss rate 9.54%);146 deaths occurred.According to expression combination,there were 89 cases of CD24 single positivity(39 deaths),68 cases of CD133 single positivity(31 deaths),81 cases of double negativity(25 deaths),and 66 cases of double positivity(51 deaths).Log-rank test showed significant differences in overall survival among the four groups(χ2=20.89,P<0.001),with CD24+/CD133+group showing the worst prognosis.CONCLUSION CD24 and CD133 exhibit high positive detection rates in GC tissues,and their co-positivity is closely associated with tumor stage progression and significantly indicates unfavorable survival outcomes.The co-expression of CD24/CD133 may reflect higher aggressiveness and metastatic potential of GC,serving as a potential prognostic marker and a direction for targeted therapeutic strategies.However,as this is a single-center retrospective study with limitations such as patient loss to follow-up and sample size,further prospective,multicenter,and mechanistic studies are required to validate its clinical applicability and biological role.展开更多
As a rising immune checkpoint on tumor cells,CD24 is closely related to tumorigenesis and progression.CD24 can directly regulate the malignant behavior of tumor cells and indirectly inhibit the function of immune cell...As a rising immune checkpoint on tumor cells,CD24 is closely related to tumorigenesis and progression.CD24 can directly regulate the malignant behavior of tumor cells and indirectly inhibit the function of immune cells in the meantime,which promotes the immune escape of tumor cells,induces cancer invasion and causes poor prognosis.The basic principle of cancer treatment is to induce cell death and inhibit cell survival.Resistance to chemoradiotherapy is a critical challenge in oncology,which limits the effectiveness of anti-cancer treatments.Many studies have shown a strong association between CD24 and chemoradiotherapy resistance in tumor cells,but the specific mechanism remains unclear.Understanding the mechanisms that CD24 induces chemoradiotherapy resistance may allow us to develop new promising therapeutic strategies to enhance the efficacy of chemoradiotherapy and improve clinical outcomes in the treatment of cancer patients.In this review,we summarized the basic characteristics and functions of CD24,as well as its role in the development of cancer.We focused on the resistance to radiotherapy and chemotherapy mediated by CD24,deciphered fundamental mechanisms and introduced existing clinical studies,with an attempt to propose potential solutions for future explorations.展开更多
背景:肿瘤干细胞与肿瘤的复发、转移以及耐药等之间存在十分密切的联系。目的:探讨CD44^+CD24^(-/low)乳腺癌干细胞活性与多药耐药的相关性。方法:运用免疫磁珠法从多药耐药乳腺癌细胞株MCF-7/ADR中分选出CD44^+CD24^(-/low)乳腺癌干细...背景:肿瘤干细胞与肿瘤的复发、转移以及耐药等之间存在十分密切的联系。目的:探讨CD44^+CD24^(-/low)乳腺癌干细胞活性与多药耐药的相关性。方法:运用免疫磁珠法从多药耐药乳腺癌细胞株MCF-7/ADR中分选出CD44^+CD24^(-/low)乳腺癌干细胞。流式细胞仪测定分选后CD44^+CD24^(-/low)乳腺癌干细胞亚群比例和细胞膜P-gp荧光强度,RT-PCR法检测多药耐药基因MDR m RNA表达水平。结果与结论:(1)获得的CD44^+CD24^(-/low)乳腺癌干细胞比例在90%以上;(2)CD44^+CD24^(-/low)细胞亚群成球比例明显强于non-CD44^+CD24^(-/low)细胞亚群;(3)CD44^+CD24^(-/low)细胞亚群的细胞膜P-gp荧光强度显著高于MFC-7/ADR细胞株(P<0.05);(4)CD44^+CD24^(-/low)细胞亚群的MDR mRNA表达水平显著高于MFC-7/ADR细胞株(P<0.05);(5)结果表明,分选得到的CD44^+CD24^(-/low)乳腺癌干细胞具有很强的体外成球能力,高表达P-gp蛋白和MDR mRNA可能是导致多药耐药的原因之一。展开更多
基金National Natural Science Foundation of China,No.82003223and China Postdoctoral Science Foundation,No.2020M671398.
文摘BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors of the digestive system worldwide,the prognosis of patients with advanced GC remains poor.AIM To evaluate the combined expression characteristics of cancer stem cell markers CD24 and CD133 in GC pathological tissues,and to explore their association with patients’clinicopathological parameters and postoperative survival outcomes.METHODS A total of 304 GC patients who underwent surgical treatment in our hospital from January 2018 to January 2020 were retrospectively included.Immunohistochemistry was used to detect the protein expression of CD24 and CD133 in tumor tissues,adjacent tissues,and normal gastric mucosa tissues.Based on staining intensity and the proportion of positive cells,expression levels were classified into low and high expression,while clinicopathological parameters were recorded.χ2 test was used to evaluate the correlation between expression and categorical variables,Spearman rank correlation analysis was performed to assess the correlation between the expression intensities of the two markers,and multivariate regression models were applied to identify independent risk factors influencing co-expression.Kaplan-Meier survival curves and Log-rank test were used to compare survival differences among groups with different expression patterns.RESULTS Among the 304 patients,155 cases(50.99%)were CD24 positive,including 91 low-expression and 64 highexpression;133 cases(43.75%)were CD133 positive,including 81 low-expression and 52 high-expression.There were 74 cases(24.34%)with double positivity and 81 cases(26.64%)with double negativity.Compared with tumor tissues,the positive rates of CD24 and CD133 in normal gastric tissues and adjacent tissues were significantly lower(P<0.05).Univariate analysis showed that co-expression of CD24 and CD133 in GC tissues was significantly correlated with tumor size,Lauren classification,T stage,N stage,and vascular invasion(P<0.05),but not with patient age,gender,tumor site,World Health Organization histological classification,or M stage(P>0.05).Further multivariate regression analysis suggested that tumor size,T stage,N stage,and vascular invasion were independent risk factors promoting CD24 and CD133 double positivity.Spearman rank correlation analysis indicated a moderate positive correlation between their expression intensities(r=0.420,P<0.001).During follow-up,29 of 304 patients were lost(loss rate 9.54%);146 deaths occurred.According to expression combination,there were 89 cases of CD24 single positivity(39 deaths),68 cases of CD133 single positivity(31 deaths),81 cases of double negativity(25 deaths),and 66 cases of double positivity(51 deaths).Log-rank test showed significant differences in overall survival among the four groups(χ2=20.89,P<0.001),with CD24+/CD133+group showing the worst prognosis.CONCLUSION CD24 and CD133 exhibit high positive detection rates in GC tissues,and their co-positivity is closely associated with tumor stage progression and significantly indicates unfavorable survival outcomes.The co-expression of CD24/CD133 may reflect higher aggressiveness and metastatic potential of GC,serving as a potential prognostic marker and a direction for targeted therapeutic strategies.However,as this is a single-center retrospective study with limitations such as patient loss to follow-up and sample size,further prospective,multicenter,and mechanistic studies are required to validate its clinical applicability and biological role.
基金supported by Health Commission of Hubei Province Scientific Research Project(No.WJ2023M068)Leading Discipline of Oncology Construction Project of Zhongnan Hospital of Wuhan University(No.XKJS202005)+8 种基金Youth Interdisciplinary Special Fund of Zhongnan Hospital of Wuhan University(No.ZNQNJC2022003)Knowledge Innovation Program of Wuhan-Shuguang Project(No.2023020201020510)Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University(ZNJC202322)Fundamental Research Funds for the Central Universities(Wuhan University,Clinical Medicine+X,2042024YXB017)Hubei Province Chinese Medicine Research Project(ZY2023Q015)Natural Science Foundation of Hubei Province(2023A FB665)Medical Young Talents Program of Hubei Province,Wuhan Young Medical Talents Training Project to L.-L.Bu,Youth Fund of the National Natural Science Foundation of China(82001644)Medical Young Talents Program of Hubei Province(7020206)“Dawn of Scientific and Technological Innovation”Program of Wuhan(703030804).
文摘As a rising immune checkpoint on tumor cells,CD24 is closely related to tumorigenesis and progression.CD24 can directly regulate the malignant behavior of tumor cells and indirectly inhibit the function of immune cells in the meantime,which promotes the immune escape of tumor cells,induces cancer invasion and causes poor prognosis.The basic principle of cancer treatment is to induce cell death and inhibit cell survival.Resistance to chemoradiotherapy is a critical challenge in oncology,which limits the effectiveness of anti-cancer treatments.Many studies have shown a strong association between CD24 and chemoradiotherapy resistance in tumor cells,but the specific mechanism remains unclear.Understanding the mechanisms that CD24 induces chemoradiotherapy resistance may allow us to develop new promising therapeutic strategies to enhance the efficacy of chemoradiotherapy and improve clinical outcomes in the treatment of cancer patients.In this review,we summarized the basic characteristics and functions of CD24,as well as its role in the development of cancer.We focused on the resistance to radiotherapy and chemotherapy mediated by CD24,deciphered fundamental mechanisms and introduced existing clinical studies,with an attempt to propose potential solutions for future explorations.
文摘背景:肿瘤干细胞与肿瘤的复发、转移以及耐药等之间存在十分密切的联系。目的:探讨CD44^+CD24^(-/low)乳腺癌干细胞活性与多药耐药的相关性。方法:运用免疫磁珠法从多药耐药乳腺癌细胞株MCF-7/ADR中分选出CD44^+CD24^(-/low)乳腺癌干细胞。流式细胞仪测定分选后CD44^+CD24^(-/low)乳腺癌干细胞亚群比例和细胞膜P-gp荧光强度,RT-PCR法检测多药耐药基因MDR m RNA表达水平。结果与结论:(1)获得的CD44^+CD24^(-/low)乳腺癌干细胞比例在90%以上;(2)CD44^+CD24^(-/low)细胞亚群成球比例明显强于non-CD44^+CD24^(-/low)细胞亚群;(3)CD44^+CD24^(-/low)细胞亚群的细胞膜P-gp荧光强度显著高于MFC-7/ADR细胞株(P<0.05);(4)CD44^+CD24^(-/low)细胞亚群的MDR mRNA表达水平显著高于MFC-7/ADR细胞株(P<0.05);(5)结果表明,分选得到的CD44^+CD24^(-/low)乳腺癌干细胞具有很强的体外成球能力,高表达P-gp蛋白和MDR mRNA可能是导致多药耐药的原因之一。
