直肠癌手术前后血清miR-24-3p和FOXQ1水平变化及其与预后的关系研究
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摘要
[目的]研究直肠癌患者手术前后血清miR-24-3p和叉头框蛋白Q1(FOXQ1)水平变化及其与预后的关系。[方法]选择2011年2月~2014年10月在我院行根治性手术切除的64例直肠癌患者(直肠癌组)作为研究对象,同时期体检健康且无肿瘤家族史的50例正常者(正常组)作为对照,检测直肠癌患者手术前后及正常组血清miR-24-3p和FOXQ1水平,分析血清miR-24-3p和FOXQ1水平与直肠癌患者临床病理特征和3年生存率的关系。[结果]直肠癌组手术前和手术后血清miR-24-3p相对表达量均显著低于正常组(P<0.05),血清FOXQ1水平均显著高于正常组(P<0.05),直肠癌患者术后血清miR-24-3p相对表达量显著升高,血清FOXQ1水平显著降低;直肠癌患者术后半年内复发患者血清miR-24-3p相对表达量显著低于未复发患者(P<0.05),血清FOXQ1水平显著高于未复发患者(P<0.05)。血清miR-24-3p表达水平与直肠癌患者TNM分期、浸润程度及淋巴结转移有关(P<0.05),血清FOXQ1水平与直肠癌患者肿瘤大小、TNM分期、浸润程度及淋巴结转移有关(P<0.05);直肠癌组患者血清miR-24-3p和FOXQ1表达水平呈显著负相关关系(r=-0.762,P=0.000);术后血清miR-24-3p升高率>48.15%患者3年生存率显著高于升高率<48.15%患者(P<0.05),血清FOXQ1降低率>33.69%患者3年生存率显著高于降低率<33.69%患者(P<0.05);FOXQ1表达水平是影响直肠癌患者预后的危险因素,而miR-24-3p表达水平是直肠癌患者预后的保护因素。[结论]直肠癌患者术后血清miR-24-3p水平显著升高,FOXQ1水平显著降低,其升高或降低程度与患者远期预后密切相关。
[Objective]To study the changes of serum miR-24-3 p and forking box protein Q1(FOXQ1)levels in rectal cancer patients before and after operation and their relationships with prognosis.[Methods]From February 2011 to October 2014,64 cases of rectal cancer patients(rectal cancer group)treated with radical resection in our hospital were selected as subjects.50 normal subjects(normal group)which were tested without family history of tumor were selected as control,the levels of serum miR-24-3 p and FOXQ1 were measured before and after operation in rectal cancer patients,analyzed the relationships between serum miR-24-3 p and FOXQ1 levels with clinicopathological features and 3-year survival rate in rectal cancer patients.[Results]The relative expressions of serum miR-24-3 p in rectal cancer group before operation and after operation were significantly lower than those in normal group(P<0.05),serum FOXQ1 levels weresignificantly higher than those in the normal group(P<0.05),the relative expression of serum miR-24-3 p in rectal cancer patients after operation increased significantly,the level of serum FOXQ1 decreased significantly;the relative expression of serum miR-24-3 p in patients with rectal cancer recurrence in six months after operation was significantly lower than that in patients without recurrence(P<0.05),serum FOXQ1 level was significantly higher than that of non recurrence patients(P<0.05).The expression of miR-24-3 p in serum was correlated with TNM stage,degree of invasion and lymph node metastasis(P<0.05),serum FOXQ1 level was correlated with tumor size,TNM stage,infiltration degree and lymph node metastasis in rectal cancer(P<0.05);there was a significant negative correlation between serum miR-24-3 p and FOXQ1 expression in rectal cancer group(r=-0.762,P=0.000);the 3-year survival rate of patients with serum miR-24-3 p increase rate>48.15% after operation was significantly higher than that of patients with increase rate<48.15%(P<0.05),the 3-year survival rate of patients with serum FOXQ1 decrease rate>33.69% was significantly higher than that of patients with decrease rate<33.69%(P<0.05);FOXQ1 expression level was a risk factor for the prognosis of rectal cancer patients,the expression level of miR-24-3 p was a protective factor for the prognosis of rectal cancer patients.[Conclusion]The level of serum miR-24-3 p increased significantly in rectal cancer patients after the operation.Meanwhile,the level of FOXQ1 decreased significantly,the degree of increase or decrease is closely related to the long-term prognosis of patients.
[Objective]To study the changes of serum miR-24-3 p and forking box protein Q1(FOXQ1)levels in rectal cancer patients before and after operation and their relationships with prognosis.[Methods]From February 2011 to October 2014,64 cases of rectal cancer patients(rectal cancer group)treated with radical resection in our hospital were selected as subjects.50 normal subjects(normal group)which were tested without family history of tumor were selected as control,the levels of serum miR-24-3 p and FOXQ1 were measured before and after operation in rectal cancer patients,analyzed the relationships between serum miR-24-3 p and FOXQ1 levels with clinicopathological features and 3-year survival rate in rectal cancer patients.[Results]The relative expressions of serum miR-24-3 p in rectal cancer group before operation and after operation were significantly lower than those in normal group(P<0.05),serum FOXQ1 levels weresignificantly higher than those in the normal group(P<0.05),the relative expression of serum miR-24-3 p in rectal cancer patients after operation increased significantly,the level of serum FOXQ1 decreased significantly;the relative expression of serum miR-24-3 p in patients with rectal cancer recurrence in six months after operation was significantly lower than that in patients without recurrence(P<0.05),serum FOXQ1 level was significantly higher than that of non recurrence patients(P<0.05).The expression of miR-24-3 p in serum was correlated with TNM stage,degree of invasion and lymph node metastasis(P<0.05),serum FOXQ1 level was correlated with tumor size,TNM stage,infiltration degree and lymph node metastasis in rectal cancer(P<0.05);there was a significant negative correlation between serum miR-24-3 p and FOXQ1 expression in rectal cancer group(r=-0.762,P=0.000);the 3-year survival rate of patients with serum miR-24-3 p increase rate>48.15% after operation was significantly higher than that of patients with increase rate<48.15%(P<0.05),the 3-year survival rate of patients with serum FOXQ1 decrease rate>33.69% was significantly higher than that of patients with decrease rate<33.69%(P<0.05);FOXQ1 expression level was a risk factor for the prognosis of rectal cancer patients,the expression level of miR-24-3 p was a protective factor for the prognosis of rectal cancer patients.[Conclusion]The level of serum miR-24-3 p increased significantly in rectal cancer patients after the operation.Meanwhile,the level of FOXQ1 decreased significantly,the degree of increase or decrease is closely related to the long-term prognosis of patients.
引文
[1]汪欣,姜勇.局部复发直肠癌的外科综合治疗进展及临床策略[J].中华胃肠外科杂志,2017,20(7):748-752.
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[9] Jing P,Zhao N,Xie N,et al.miR-24-3p/FGFR3Signaling as a Novel Axis Is Involved in Epithelial-Mesenchymal Transition and Regulates Lung Adenocarcinoma Progression[J].J Immunol Res,2018:2834109.
[10]Gao Y,Liu Y,Du L,et al.Down-regulation of miR-24-3p in colorectal cancer is associated with malignant behavior[J].Med Oncol,2015,32(1):362.
[11]Guo J,Yan Y,Yan Y,et al.Tumor-associated macrophages induce the expression of FOXQ1to promote epithelial-mesenchymal transition and metastasis in gastric cancer cells[J].Oncol Rep,2017,38(4):2003-2010.
[12]Huang W,Chen Z,Shang X,et al.Sox12,a direct target of FoxQ1,promotes hepatocellular carcinoma metastasis through up-regulating Twist1and FGFBP1[J].Hepatology,2015,61(6):1920-1933.
[13]Christensen J,Bentz S,Sengstag T,et al.FOXQ1,a novel target of the Wnt pathway and a new marker for activation of Wnt signaling in solid tumors.[J].Plos One,2013,8(3):e60051.
[14]郑成军,赵雪云,王健,等.264例直肠癌预后的影响因素分析[J].重庆医学,2014(1):122-124.
[15]Church J M.Extent of mesorectal invasion is a prognostic indicator in T3rectal carcinoma[J].Anz J Surg,2015,72(7):483-487.
[2]宋应周.根治性直肠癌术后局部复发的预后因素分析[J].临床合理用药杂志,2015(16):116-117.
[3] Leva G D,Garofalo M,Croce C M.MicroRNAs in Cancer[J].Ann Rev Pathol,2014,9(1):287-314.
[4]屈昌民,李连勇,梁淑文,等.直肠腺瘤和直肠癌中microRNA表达谱差异[J].中华临床医师杂志(电子版),2013,7(12):29-33.
[5]李杨,徐敏,LiYang,等.叉头框蛋白Q1与消化系统肿瘤的关系[J].中华肝胆外科杂志,2016,22(5):351-354.
[6] Martin E C,Elliott S,Rhodes L V,et al.Preferential star strand biogenesis of pre-miR-24-2targets PKC-alpha and suppresses cell survival in MCF-7breast cancer cells[J].Mol Carcinog,2014,53(1):38-48.
[7] Ma Y,She X G,Ming Y Z,et al.miR-24promotes the proliferation and invasion of HCC cells by targeting SOX7[J].Tumour Bio,2014,35(11):10731-10736.
[8] Ye S B,Zhang H,Cai T T,et al.Exosomal miR-24-3p impedes T-cell function by targeting FGF11and serves as a potential prognostic biomarker for nasopharyngeal carcinoma[J].J Pathol,2016,240(3):329-340.
[9] Jing P,Zhao N,Xie N,et al.miR-24-3p/FGFR3Signaling as a Novel Axis Is Involved in Epithelial-Mesenchymal Transition and Regulates Lung Adenocarcinoma Progression[J].J Immunol Res,2018:2834109.
[10]Gao Y,Liu Y,Du L,et al.Down-regulation of miR-24-3p in colorectal cancer is associated with malignant behavior[J].Med Oncol,2015,32(1):362.
[11]Guo J,Yan Y,Yan Y,et al.Tumor-associated macrophages induce the expression of FOXQ1to promote epithelial-mesenchymal transition and metastasis in gastric cancer cells[J].Oncol Rep,2017,38(4):2003-2010.
[12]Huang W,Chen Z,Shang X,et al.Sox12,a direct target of FoxQ1,promotes hepatocellular carcinoma metastasis through up-regulating Twist1and FGFBP1[J].Hepatology,2015,61(6):1920-1933.
[13]Christensen J,Bentz S,Sengstag T,et al.FOXQ1,a novel target of the Wnt pathway and a new marker for activation of Wnt signaling in solid tumors.[J].Plos One,2013,8(3):e60051.
[14]郑成军,赵雪云,王健,等.264例直肠癌预后的影响因素分析[J].重庆医学,2014(1):122-124.
[15]Church J M.Extent of mesorectal invasion is a prognostic indicator in T3rectal carcinoma[J].Anz J Surg,2015,72(7):483-487.