宫颈癌组织中miR-337-3p、TCF12表达与患者术后生存期的相关性研究

Correlation between the expression of miR-337-3p and TCF12 in cervical cancer tissues and postoperative survival of patients

摘要

目的 探索宫颈癌患者癌组织中微小RNA-337-3p(miR-337-3p)、转录因子12(TCF12)的表达情况及其与患者术后生存期的相关性,为宫颈癌诊治提供新的研究方向.方法 选取2016年5月至2017年5月在某中心行手术治疗的110例宫颈癌患者作为研究对象,采集癌组织与癌旁组织并分别作为癌组织组(n=110)和癌旁组织组(n=110).采用实时荧光定量PCR(qRT-PCR)法测定癌组织组与癌旁组织组miR-337-3p、TCF12 mRNA水平;通过免疫组化评估TCF12蛋白阳性率.采用Pearson分析miR-337-3p与TCF12 mRNA水平的相关性;采用Kaplan-Meier法分析miR-337-3p mRNA水平、TCF12阳性率与宫颈癌患者预后生存期的关系;采用Cox生存分析影响宫颈癌患者预后的相关因素.结果 与癌旁组织组相比,宫颈癌组miR-337-3p mRNA水平降低,TCF12 mRNA水平升高(t=8.930、9.838,P<0.05);宫颈癌组织中TCF12蛋白阳性表达率为77.27%,显著高于癌旁组织(38.18%)(P<0.05);miR-337-3p与TCF12 mRNA表达呈负相关(r=-0.519,P<0.05);miR-337-3p、TCF12表达均与分化程度(中高分化、低分化)、FIGO分期(Ⅰ期、Ⅱ期)、间质浸润(是、否)、淋巴结转移(是、否)相关(χ²值分别在6.638~14.175之间及4.009~21.706之间,均P<0.05);miR-337-3p低表达患者5年内累积生存率(75.00%)低于miR-337-3p高表达患者(90.70%)(logRank χ²=4.720,P=0.030);TCF12阴性患者5年内累积生存率(97.20%)高于TCF12阳性患者(81.10%)(logRank χ²=7.150,P=0.007);Cox回归分析显示,与miR-337-3p低表达患者相比,miR-337-3p高表达患者复发风险更低,HR及95%CI为0.901(0.835~0.973);与TCF表达阴性的患者相比,TCF12表达阳性的患者术后复发风险更高,HR及95%CI为2.983(1.346~6.611)(均P<0.05).结论 TCF12阳性、miR-337-3p低表达与患者术后宫颈癌复发显著相关,提示两者可作为评估宫颈癌复发的指标.

Abstract

Objective To explore the expression of microRNA-337-3p (miR-337-3p) and transcription factor 12 (TCF12) in the cancer tissues of cervical cancer patients and their correlation with postoperative survival, so as to provide a new research direction for the diagnosis and treatment of cervical cancer. Methods A total of 110 cervical cancer patients who underwent surgery in a center from May 2016 to May 2017 were selected as the study subjects, and cancer tissues and adjacent tissues were collected as cancer tissue group (n=110) and adjacent tissue group (n=110), respectively. The mRNA levels of miR-337-3p and TCF12 in cancer tissue group and adjacent tissue group were determined by real-time quantitative PCR (qRT-PCR). The positive rate of TCF12 protein was assessed by immunohistochemistry. Pearson was used to analyze the correlation between miR-337-3p and TCF12 mRNA levels. Kaplan-Meier method was used to analyze the relationship between miR-337-3p mRNA level and TCF12 positive rate and prognostic survival of cervical cancer patients. Cox survival analysis was used to analyze the prognosis of cervical cancer patients. Results Compared with the adjacent tissue group, the mRNA level of miR-337-3p in the cervical cancer group decreased and the mRNA level of TCF12 increased (t=8.930, 9.838, P<0.05), the positive expression rate of TCF12 protein in cervical cancer tissue was 77.27%, which was significantly higher than that in adjacent tissue (38.18%) (P<0.05), and miR-337-3p was negatively correlated with TCF12 mRNA expression (r=-0.519, P<0.05). The expressions of miR-337-3p and TCF12 were correlated with the degree of differentiation (moderately high differentiation, low differentiation), FIGO stage (stage Ⅰ, stage Ⅱ), interstitial infiltration (yes, no), and lymph node metastasis (χ ² values were between 6.638-14.175 and 4.009-21.706, respectively, both P<0.05). The cumulative survival rate within 5 years (75.00%) of patients with low expression of miR-337-3p was lower than that of patients with high expression of miR-337-3p (90.70%) (logrank χ ²=4.720, P=0.030). The cumulative survival rate within 5 years of TCF12-negative patients (97.20%) was higher than that of TCF12-positive patients (81.10%) (logrank χ ²=7.150, P=0.007). Cox regression analysis showed that compared with patients with low miR-337-3p expression, patients with high miR-337-3p expression had a lower risk of recurrence, with HR and 95% CI of 0.901 (0.835-0.973). Compared with patients with negative TCF expression, patients with positive TCF12 expression had a higher risk of postoperative recurrence, with HR and 95% CI of 2.983 (1.346-6.611) (all P<0.05). Conclusion TCF12 positivity and low expression of miR-337-3p were significantly correlated with postoperative cervical cancer recurrence, suggesting that they could be used as indicators to evaluate cervical cancer recurrence.

关键词

宫颈癌 / 微小RNA-337-3p / 转录因子12 / 复发风险

Key words

cervical cancer / microRNA-337-3p / transcription factor 12 / risk of recurrence

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