摘要
目的:探讨鳞状上皮热休克蛋白53 (CRNN)在食管鳞状细胞癌(ESCC)中的表达情况,并评估其对ESCC细胞Eca9706细胞生物学行为的影响。方法:采用免疫组织化学法检测CRNN蛋白在93例ESCC组织和101例癌旁正常食管上皮组织中的表达,并分析CRNN表达水平与ESCC患者临床病理特征及生存预后之间的关系。采用受试者工作特征(ROC)曲线分析CRNN水平对ESCC的预测效能。将Eca9706细胞分为对照组和CRNN组(过表达CRNN),采用细胞计数试剂盒(CCK-8)实验检测2组Eca9706细胞增殖活性,Transwell小室实验检测2组Eca9706细胞迁移细胞数,平板克隆形成实验检测2组Eca9706细胞克隆形成数,流式细胞术检测2组Eca9706细胞凋亡率。结果:与癌旁正常食管上皮组织比较,ESCC组织中CRNN蛋白表达强度明显降低(χ^(2)=23.476,P<0.001);ESCC组织中CRNN蛋白表达下调与肿瘤部位(χ^(2)=5.353,P=0.021)和组织学分级(χ^(2)=4.434,P=0.035)存在关联,与患者年龄(χ^(2)=0.102,P=0.750)、性别(χ^(2)=0.050,P=0.822)、肿瘤分期(χ^(2)=0.047,P=0.828)和淋巴结转移(χ^(2)=0.553,P=0.457)均无关联。生存分析,CRNN蛋白高表达组ESCC患者预后优于CRNN蛋白低表达组(P=0.013)。单因素Cox比例风险回归分析,ESCC患者总生存率与CRNN蛋白表达水平[风险比(HR)=0.198,95%置信区间(CI):0.047~0.842,P=0.028]和肿瘤分期(HR=2.479,95%CI:1.247~4.929,P=0.010)存在关联;多因素Cox比例风险回归分析,CRNN蛋白表达水平(HR=0.213,95%CI:0.050~0.895,P=0.035)和肿瘤分期(HR=2.391,95%CI:1.198~4.772,P=0.013)是ESCC预后的独立因素。与对照组比较,CRNN组Eca9706细胞增殖活性明显降低(P=0.004),克隆形成数明显减少(P=0.002),迁移细胞数明显降低(P=0.002),细胞凋亡率明显升高(P=0.006)。结论:CRNN蛋白在ESCC组织中表达水平较低,提示患者预后不良。过表达CRNN蛋白可能抑制ESCC细胞的增殖、迁移和侵袭能力,并促进其凋亡。
Objective:To investigate the expression of squamous cell heat shock protein 53(CRNN)in esophageal squamous cell carcinoma(ESCC),and toevaluate its impact on the biological behavior of ESCC cells Eca9706.Methods:Immunohistochemical method was used to detect the expression of CRNN protein in 93 ESCC tissues and 101 normal esophageal epithelial tissues adjacent to cancer,and the associations of CRNN expression levels with the clinical pathological characteristics and survival prognosis of ESCC patients were analyzed.Receiver operating characteristic(ROC)curve was used to analyze the predictive performance of CRNN expression level on ESCC.The Eca9706 cells were divided into control group and CRNN group(overexpression of CRNN).Cell counting kit-8(CCK-8)assay was used to detect the proliferation activities of Eca9706 cells in two groups;Transwell chamber assay was used to detect the numbers of migration cells of Eca9706 cells in two groups;plate clone formation assay was used to assess the numbers of clone formation of Eca9706 cells in two groups;flow cytometry was used to detect the apoptotic rates of Eca9706 cells in two groups.Results:Compared with adjacent normal esophageal epithelial tissue,the expression intensity of CRNN protein in ESCC tissue was significantly decreased(χ^(2)=23.476,P<0.001).The downregulation of CRNN protein expression in ESCC patients was associated with tumor location(χ^(2)=5.353,P=0.021)and histological grade(χ^(2)=4.434,P=0.035),but not with age(χ^(2)=0.102,P=0.750),gender(χ^(2)=0.050,P=0.822),tumor stage(χ^(2)=0.047,P=0.828)or lymph node metastasis(χ^(2)=0.553,P=0.457).Survival analysis showed that ESCC patients in high expression of CRNN protein group had better prognosis than those in low expression of CRNN protein group(P=0.013).Univariable Cox proportional hazards regression analysis showed the associations between overall survival rate in ESCC patients and the expression level of CRNN protein[hazard ratio(HR)=0.198,95%confidence interval(CI):0.047-0.842,P=0.028]and tumor stage(HR=2.479,95%CI:1.247-4.929,P=0.010).Multivariable Cox regression analysis showed that the expression level of CRNN protein(HR=0.213,95%CI:0.050-0.895,P=0.035)and tumor stage(HR=2.391,95%CI:1.198-4.772,P=0.013)were independent factors for the prognosis of ESCC.Compared with control group,the proliferation activity of cells in CRNN group was significantly decreased(P=0.004),the number of clone formation was decreased(P=0.002),the number of migration cells was decreased(P=0.002),and the apoptotic rate was significantly increased(P=0.006).Conclusion:Low expression level of CRNN protein suggests poor prognosis for the ESCC patients.Overexpression of CRNN may inhibit the proliferation,migration and invasion abilities of ESCC cells,and promote their apoptosis.
作者
孙淑妍
张华坤
周紫如
李锋
崔晓宾
SUN Shuyan;ZHANG Huakun;ZHOU Ziru;LI Feng;CUI Xiaobin(Department of Pathology,School of Medical Sciences,Shihezi University,Shihezi 832002,China;Department of Pathology,Gulou Hospital,School of Medical Sciences,Nanjing University,Nanjing 210008,China)
出处
《吉林大学学报(医学版)》
北大核心
2025年第2期275-283,共9页
Journal of Jilin University:Medicine Edition
基金
国家自然科学基金项目(82160542,82273020)
南京大学医学院附属鼓楼医院临床研究专项资金项目(2023-LCYJ-MS-17)。
