恶性肿瘤严重威胁人类健康,其发病机制复杂多样。分化簇抗原(cluster of differentiation,CD)24是一种近年来备受关注的糖基化膜蛋白,其在人体正常组织中参与细胞生理功能调控、免疫稳态维持、组织发育与分化等生理过程,而在乳腺癌、卵...恶性肿瘤严重威胁人类健康,其发病机制复杂多样。分化簇抗原(cluster of differentiation,CD)24是一种近年来备受关注的糖基化膜蛋白,其在人体正常组织中参与细胞生理功能调控、免疫稳态维持、组织发育与分化等生理过程,而在乳腺癌、卵巢癌、肺癌等多种恶性肿瘤组织中呈现异常高表达。CD24为肿瘤干细胞(cancer stem cell,CSC)核心标志物,与肿瘤细胞的恶性生物学行为、肿瘤恶性进展、治疗耐受及不良预后密切相关。CD24可通过CD24/唾液酸结合免疫球蛋白样凝集素-10(sialic acid-binding immunoglobulin-like lectin-10,Siglec-10)通路抑制巨噬细胞吞噬、重塑肿瘤免疫抑制微环境、激活促癌信号通路、调控肿瘤细胞黏附转移等多重机制参与肿瘤发生和发展,且在血液肿瘤中表现出独特的功能双重性。系统探究CD24在不同恶性肿瘤中的表达特征、作用机制及预后价值,发现靶向CD24的单克隆抗体等治疗策略有良好的临床应用前景,且CD24相较经典免疫检查点具有低血液毒性的潜在优势。研究证实CD24可作为恶性肿瘤精准诊断、预后评估的潜在标志物及个体化治疗的新靶点,具有重要的基础研究意义与临床转化价值。展开更多
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
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.
