摘要
目的 探讨长链非编码RNA(lncRNA)同源异形盒基因A11反义RNA(HOXA11-AS)和微小RNA-98-5p(miR-98-5p)在乳腺癌中的表达,并分析其与临床病理特征的关系.方法 回顾性选取2014年1月至2016年10月青岛大学附属青岛市中心医院(青岛市肿瘤医院)接收的120例乳腺癌患者作为研究对象.收集乳腺癌患者的临床病理资料,如年龄、肿瘤大小、TNM分期、病理分级、病理类型、孕激素受体(PR)表达、人类表皮生长因子受体2(HER-2)表达、雌激素受体(ER)表达、Ki-67表达等.采用实时荧光定量PCR法检测所有组织HOXA11-AS、miR-98-5p表达水平.比较HOXA11-AS、miR-98-5p在乳腺癌组织及乳腺癌各分子分型上的表达水平.采用Spearman法分析癌组织中HOXA11-AS与miR-98-5p的相关性.分析HOXA11-AS、miR-98-5p表达水平与乳腺癌临床病理特征关系.结果 癌组织中HOXA11-AS的水平为2.21±0.53,较癌旁组织(1.02±0.21)显著升高,而miR-98-5p水平为0.58±0.12,较癌旁组织(1.03±0.19)显著降低,差异均有统计学意义(P＜0.05).HER-2阳性、Luminal A型、Luminal B型、Basal-like型的癌组织中HOXA11-AS表达水平较癌旁组织显著升高,miR-98-5p表达水平显著降低,差异均有统计学意义(P＜0.05).以表达水平将乳腺癌患者分别分为HOXA11-AS高表达组(n=67)和HOXA11-AS 低表达组(n=53),miR-98-5p 低表达组(n=63)和 miR-98-5p 高表达组(n=57).HOXA11-AS、miR-98-5p均与乳腺癌TNM分期、HER-2表达、Ki-67表达、ER表达、PR表达相关(P＜0.05).乳腺癌组织中HOXA11-AS与miR-98-5p表达水平呈负相关(r=-0.571,P＜0.05).Kaplan-Meier分析表明,HOXA11-AS低表达组的平均生存时间为(53.61±1.58)个月,高于HOXA11-AS高表达组[(42.11±2.14)个月],差异有统计学意义(P＜0.05);miR-98-5p高表达组的平均生存时间为(52.65±1.62)个月,高于miR-98-5p低表达组[(42.25±2.23)个月],差异有统计学意义(P＜0.05).TNM分期、病理分级、病理类型、PR表达、HER-2表达、ER表达、Ki-67、HOXA11-AS、miR-98-5p是乳腺癌患者预后的独立危险因素(P＜0.05).结论 乳腺癌组织HOXA11-AS呈高表达、miR-98-5p呈低表达,HOXA11-AS、miR-98-5p与患者生存期密切相关,是影响乳腺癌预后的独立因素,可能成为新的乳腺癌治疗靶点.
Abstract
Objective To investigate the expression of long non-coding RNA(lncRNA)Homeobox A11 antisense RNA(HOXA11-AS)and microRNA-98-5p(miR-98-5p)in breast cancer,and to analyze their relationship with the clinicopathological characteristics.Methods A total of 120 patients with breast cancer admitted to Qingdao Central Hospital Affiliated to Qingdao University(Qingdao Cancer Hospi-tal)from January 2014 to October 2016 were retrospectively selected as the study subjects.The clinicopathological data of breast cancer patients were collected,such as age,tumor size,TNM stage,pathological grade,pathological type,progesterone receptor(PR)expression,human epi-dermal growth factor receptor 2(HER-2)expression,estrogen receptor(ER)expression,Ki-67 expression,etc.The expression levels of HOXA11-AS and miR-98-5p in all tissues were detected using real-time fluorescent quantitative PCR method.The expression levels of HOXA11-AS and miR-98-5p in breast cancer tissues and molecular subtypes of breast cancer were compared.The correlation between HOXA11-AS and miR-98-5p in cancer tissues was analyzed by Spearman method.The relationship between the expression levels of HOXA11-AS,miR-98-5p and the clinicopathological characteristics of breast cancer was analyzed.Results The level of HOXA11-AS in cancer tis-sues was 2.21±0.53,which was significantly higher than that in adjacent tissues(1.02±0.21),while the level of miR-98-5p in cancer tis-sues was 0.58±0.12,which was significantly lower than that in adjacent tissues(1.03±0.19),and the differences were statistically significant(P＜0.05).The expression levels of HOXA11-AS in HER-2 positive,Luminal A,Luminal B and Basal-like cancer tissues were signifi-cantly higher than those in adjacent tissues,and the expression level of miR-98-5 p was significantly lower,the differences were statistically sig-nificant(P＜0.05).According to the expression level,breast cancer patients were divided into the HOXA11-AS high expression group(n=67)and the low expression group(n=53),the miR-98-5p low expression group(n=63)and the miR-98-5p high expression group(n=57).Both HOXA11-AS and miR-98-5p were related to breast cancer TNM staging,HER-2 expression,Ki-67 expression,ER ex-pression and PR expression(P＜0.05).The expression levels of HOXA11-AS and miR-98-5p in breast cancer tissues were negatively cor-related(r=-0.571,P＜0.05).Kaplan-Meier analysis showed that the average survival time of the HOXA11-AS low expression group was(53.61±1.58)months,which was higher than that of the HOXA11-AS high expression group[(42.11±2.14)months],and the difference was statistically significant(P＜0.05).The average survival time of the miR-98-5p high expression group was(52.65±1.62)months,which was higher than that of miR-98-5p low expression group[(42.25±2.23)months],and the difference was statistically significant(P＜0.05).TNM stage,pathological grading,type of pathology,PR expression,HER-2 expression,ER expression,Ki-67,HOXA11-AS,miR-98-5p were independent factors for prognosis of breast cancer patients(P＜0.05).Conclusion HOXA11-AS is highly expressed in breast cancer tissues,and miR-98-5p is low expressed,HOXA11-AS and miR-98-5p are closely related to patient survival,are independ-ent factors affecting the prognosis of breast cancer,and may become new breast cancer treatment targets.
基金项目
山东省医药卫生科技发展计划项目(2017WD253)
NETL
NSTL
万方数据