[目的]探究S100A12、RAGE在宫颈癌细胞增殖、迁移和凋亡中的作用。[方法]采集2022年4月-2023年5月宫颈癌病例癌组织及癌旁组织的石蜡标本,用免疫组化法检测S100A12的表达。随机将SiHa细胞分为空白组(无转染)、阴性对照组(转染空白质粒)...[目的]探究S100A12、RAGE在宫颈癌细胞增殖、迁移和凋亡中的作用。[方法]采集2022年4月-2023年5月宫颈癌病例癌组织及癌旁组织的石蜡标本,用免疫组化法检测S100A12的表达。随机将SiHa细胞分为空白组(无转染)、阴性对照组(转染空白质粒)和敲低组(转染siRNA),构建相应细胞模型。免疫组化检测S100A12在宫颈癌组织和癌旁组织的表达情况;实时荧光定量PCR检测S100A12 mRNA与RAGE mRNA水平;Western Blot检测PCNA、S100A12的蛋白表达水平;通过MTT法以及细胞集落形成实验检测细胞的生长情况,通过Transwell实验检测细胞迁移情况;流式细胞术检测细胞凋亡情况。[结果]S100A12在宫颈癌组织中蛋白表达水平高于癌旁组织(82.47%±0.35%vs 11.34%±0.17%,P<0.05)。敲低组细胞中S100A12、RAGE的mRNA和蛋白表达均低于空白组与阴性对照组(1.16±0.12 vs 1.13±0.16 vs 0.17±0.08;2.57±0.13 vs 2.67±0.13 vs 0.65±0.05;P<0.05)。敲低组细胞的增殖能力、集落形成数量和迁移能力均低于空白组、阴性对照组(P<0.05)。敲低组细胞的凋亡率高于空白组、阴性对照组(1.16%±0.09%vs 1.78%±0.03%vs 11.53%±0.09%;P<0.05)。[结论]宫颈癌组织中RAGE与S100A12表达量显著升高,下调S100A12后,癌细胞的增殖、迁移能力减弱,凋亡率增加,并且RAGE表达受到抑制。因此,S100A12对宫颈癌细胞的抑制作用与调控RAGE相关。展开更多
BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignancies in elderly populations,and chemotherapy resistance remains a critical clinical challenge.Emerging evidence highlights the interplay between ...BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignancies in elderly populations,and chemotherapy resistance remains a critical clinical challenge.Emerging evidence highlights the interplay between chronic inflammation,gut microbiome dysbiosis,and CRC progression.Proinflammatory cytokines[e.g.,interleukin(IL)-6,tumor necrosis factor-alpha(TNF-α)]and mediators like S100 calcium-binding protein A12(S100A12)/soluble receptor for advanced glycation end products(sRAGE)are implicated in tumorigenesis,while gut microbial imbalances may exacerbate inflammatory microenvironments conducive to che-motherapy resistance.However,the triad relationship between S100A12/sRAGE,gut microbiota profiles,and chemotherapy efficacy in elderly patients with CRC remains unexplored,limiting biomarker-driven therapeutic strategies.AIM To analyze the correlation between serum levels of S100A12,sRAGE,gut microbiome dysbiosis,and systemic inflammation in elderly patients with CRC and to assess their predictive value for chemotherapy efficacy.METHODS A retrospective analysis was conducted on the clinical data of 120 elderly patients with advanced-stage CRC who visited our hospital from August 2023 to May 2024.These patients were enrolled in the study group.Additionally,120 healthy individuals undergoing routine health check-ups during the same period were selected as the control group.Serum S100A12,sRAGE,IL-6,and TNF-αlevels were measured by ELISA,and fresh stool samples were collected before chemotherapy to analyze gut microbiome composition in the study group.Follow-up observations were conducted after chemotherapy.Pearson correlation analysis was used to explore the relationship between serum S100A12,sRAGE levels,and gut microbiome dysbiosis in patients with CRC.The predictive diagnostic value of pre-chemotherapy serum S100A12 and sRAGE levels for chemotherapy efficacy was assessed using receiver operating characteristic curves.RESULTS Pre-chemotherapy serum S100A12,sRAGE,IL-6,and TNF-αlevels were significantly elevated in patients with CRC vs controls(all P<0.05).These biomarkers progressively increased with microbiota dysbiosis severity(severe vs mild dysbiosis:S100A12:340.26±52.39μg/L vs 302.53±56.97μg/L;sRAGE:525.64±37.32 ng/L vs 441.38±48.73 ng/L,P<0.05)and correlated strongly with IL-6(r=0.712)and TNF-α(r=0.698).Post-chemotherapy,biomarker levels decreased(P<0.05),coinciding with beneficial microbiota recovery(Bifidobacterium 176%,Lactobacillus 153%)and pathogenic taxa reduction(Escherichia coli 62%).The combined S100A12/sRAGE model predicted chemotherapy resistance with an area under the curve of 0.914(sensitivity=86.07%,specificity=88.89%),outper-forming individual biomarkers.CONCLUSION Elevated serum S100A12 and sRAGE in elderly patients with CRC reflected gut microbiome dysbiosis and systemic inflammation,driven by IL-6/TNF-αsignaling.Their post-chemotherapy decline parallels microbiota restoration,supporting a microbiome-inflammation-biomarker axis.The combined biomarker model offers robust clinical utility for chemotherapy efficacy prediction and personalized therapeutic strategies.展开更多
文摘[目的]探究S100A12、RAGE在宫颈癌细胞增殖、迁移和凋亡中的作用。[方法]采集2022年4月-2023年5月宫颈癌病例癌组织及癌旁组织的石蜡标本,用免疫组化法检测S100A12的表达。随机将SiHa细胞分为空白组(无转染)、阴性对照组(转染空白质粒)和敲低组(转染siRNA),构建相应细胞模型。免疫组化检测S100A12在宫颈癌组织和癌旁组织的表达情况;实时荧光定量PCR检测S100A12 mRNA与RAGE mRNA水平;Western Blot检测PCNA、S100A12的蛋白表达水平;通过MTT法以及细胞集落形成实验检测细胞的生长情况,通过Transwell实验检测细胞迁移情况;流式细胞术检测细胞凋亡情况。[结果]S100A12在宫颈癌组织中蛋白表达水平高于癌旁组织(82.47%±0.35%vs 11.34%±0.17%,P<0.05)。敲低组细胞中S100A12、RAGE的mRNA和蛋白表达均低于空白组与阴性对照组(1.16±0.12 vs 1.13±0.16 vs 0.17±0.08;2.57±0.13 vs 2.67±0.13 vs 0.65±0.05;P<0.05)。敲低组细胞的增殖能力、集落形成数量和迁移能力均低于空白组、阴性对照组(P<0.05)。敲低组细胞的凋亡率高于空白组、阴性对照组(1.16%±0.09%vs 1.78%±0.03%vs 11.53%±0.09%;P<0.05)。[结论]宫颈癌组织中RAGE与S100A12表达量显著升高,下调S100A12后,癌细胞的增殖、迁移能力减弱,凋亡率增加,并且RAGE表达受到抑制。因此,S100A12对宫颈癌细胞的抑制作用与调控RAGE相关。
文摘BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignancies in elderly populations,and chemotherapy resistance remains a critical clinical challenge.Emerging evidence highlights the interplay between chronic inflammation,gut microbiome dysbiosis,and CRC progression.Proinflammatory cytokines[e.g.,interleukin(IL)-6,tumor necrosis factor-alpha(TNF-α)]and mediators like S100 calcium-binding protein A12(S100A12)/soluble receptor for advanced glycation end products(sRAGE)are implicated in tumorigenesis,while gut microbial imbalances may exacerbate inflammatory microenvironments conducive to che-motherapy resistance.However,the triad relationship between S100A12/sRAGE,gut microbiota profiles,and chemotherapy efficacy in elderly patients with CRC remains unexplored,limiting biomarker-driven therapeutic strategies.AIM To analyze the correlation between serum levels of S100A12,sRAGE,gut microbiome dysbiosis,and systemic inflammation in elderly patients with CRC and to assess their predictive value for chemotherapy efficacy.METHODS A retrospective analysis was conducted on the clinical data of 120 elderly patients with advanced-stage CRC who visited our hospital from August 2023 to May 2024.These patients were enrolled in the study group.Additionally,120 healthy individuals undergoing routine health check-ups during the same period were selected as the control group.Serum S100A12,sRAGE,IL-6,and TNF-αlevels were measured by ELISA,and fresh stool samples were collected before chemotherapy to analyze gut microbiome composition in the study group.Follow-up observations were conducted after chemotherapy.Pearson correlation analysis was used to explore the relationship between serum S100A12,sRAGE levels,and gut microbiome dysbiosis in patients with CRC.The predictive diagnostic value of pre-chemotherapy serum S100A12 and sRAGE levels for chemotherapy efficacy was assessed using receiver operating characteristic curves.RESULTS Pre-chemotherapy serum S100A12,sRAGE,IL-6,and TNF-αlevels were significantly elevated in patients with CRC vs controls(all P<0.05).These biomarkers progressively increased with microbiota dysbiosis severity(severe vs mild dysbiosis:S100A12:340.26±52.39μg/L vs 302.53±56.97μg/L;sRAGE:525.64±37.32 ng/L vs 441.38±48.73 ng/L,P<0.05)and correlated strongly with IL-6(r=0.712)and TNF-α(r=0.698).Post-chemotherapy,biomarker levels decreased(P<0.05),coinciding with beneficial microbiota recovery(Bifidobacterium 176%,Lactobacillus 153%)and pathogenic taxa reduction(Escherichia coli 62%).The combined S100A12/sRAGE model predicted chemotherapy resistance with an area under the curve of 0.914(sensitivity=86.07%,specificity=88.89%),outper-forming individual biomarkers.CONCLUSION Elevated serum S100A12 and sRAGE in elderly patients with CRC reflected gut microbiome dysbiosis and systemic inflammation,driven by IL-6/TNF-αsignaling.Their post-chemotherapy decline parallels microbiota restoration,supporting a microbiome-inflammation-biomarker axis.The combined biomarker model offers robust clinical utility for chemotherapy efficacy prediction and personalized therapeutic strategies.
