lncRNA HOXA11-AS和miR-98-5p在乳腺癌组织中的表达及临床意义

Expression and clinical significance of lncRNA HOXA11-AS and miR-98-5p in breast cancer

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。

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 Hospital)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 epidermal 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 tissues 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 tissues 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 significantly higher than those in adjacent tissues,and the expression level of miR-98-5 p was significantly lower,the differences were statistically significant(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 expression and PR expression(P<0.05).The expression levels of HOXA11-AS and miR-98-5p in breast cancer tissues were negatively correlated(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 independent factors affecting the prognosis of breast cancer,and may become new breast cancer treatment targets.