Clinical significance of miR-148a expression in patients with esophageal squamous cell cancer

doi:10.3877/cma.j.issn.2095-8773.2014.01.0010

Abstract

Abstract:

Objective

To detect the expression of miR-148a in the tissues of esophageal squamous cell cancer, and investigate its clinicopathological and prognostic significance.

Methods

The tumor tissue specimens of 75 patients with esophageal squamous cell cancer undergoing subtotal esophagectomy and regional lymph node dissection between January 2009 and December 2009 at Qilu Hospital, Shandong University were obtained. Real-time PCR was performed to detect the expression of miR-148a. All statistical analyses were done with SPSS 18.0 software. χ² test was used to examine the association between miR-148a expression and clinicopathological factors. Survival curves were plotted by the Kaplan-Meier method, and survival differences were compared by the Log-rank test. Cox regression multivariate analysis was conducted to identify significantly independent prognostic factors.

Results

The low expression of miR-148a was detected in 32(42.7%, 32/75) cases, and significantly correlated with infiltration depth (χ²=8.149, P=0.017), lymph node metastasis (χ²=4.151, P=0.042) and pathological stage (χ²=6.474, P=0.039). The overall 3-year survival after operation was 70.7%, and univariate survival analysis demonstrated that patients with low expression of miR-148a had significantly lower 3-year overall survival than those with high expression of miR-148a (53.1% vs 83.7%, χ²=9.136, P=0.003). Cox regression multivariate survival analysis indicated that infiltration depth (95%CI: 1.015-2.799, P=0.044) and lymph node metastasis (95%CI: 1.285-4.796, P=0.007) were independent predictors for 3-year overall survival.

Conclusions

Aberrant low expression of miR-148a exists in tissues of esophageal squamous cell cancer, and is significantly associated with tumor progression and unfavorable prognosis. miR-148a may serve as an indicator of progression and poor prognosis of esophageal squamous cell cancer.

Key words: miR-148a, Esophageal squamous cell cancer, Progression, Prognosis

Shuhai Li, Hui Tian, Weiming Yue, Lin Li, Cun Gao, Libo Si, Wensi Hu, Lei Qi, Ming Lu, Jingjing Cui, Guanqing Chen. Clinical significance of miR-148a expression in patients with esophageal squamous cell cancer[J]. Chinese Journal of Thoracic Surgery(Electronic Edition), 2014, 01(01): 48-52.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhxbwkdzzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-8773.2014.01.0010

https://zhxbwkdzzz.cma-cmc.com.cn/EN/Y2014/V01/I01/48

Figures/Tables 3

References 26

[1]	Sano A, Kato H, Sakurai S, et al. CD24 expression is a novel prognostic factor in esophageal squamous cell carcinoma[J]. Ann Surg Oncol, 2009，16(2)：506-514.
[2]	Ren Y, Cao B, Law S, et al. Hepatocyte growth factor promotes cancer cell migration and angiogenic factors expression: a prognostic marker of human esophageal squamous cell carcinomas[J]. Clin Cancer Res, 2005，11(17)：6190-6197.
[3]	Mariette C, Balon JM, Piessen G, et al. Pattern of recurrence following complete resection of esophageal carcinoma and factors predictive of recurrent disease[J]. Cancer, 2003，97(7)：1616-1623.
[4]	Law S, Kwong DL, Kwok KF, et al. Improvement in treatment results and long-term survival of patients with esophageal cancer: impact of chemoradiation and change in treatment strategy[J]. Ann Surg, 2003，238(3)：339-347.
[5]	Okawa T, Naomoto Y, Nobuhisa T, et al. Heparanase is involved in angiogenesis in esophageal cancer through induction of cyclooxygenase-2[J]. Clin Cancer Res, 2005；11(22)：7995-8005.
[6]	Shih CH, Ozawa S, Ando N, et al. Vascular endothelial growth factor expression predicts outcome and lymph node metastasis in squamous cell carcinoma of the esophagus[J]. Clin Cancer Res, 2000；6(3)：1161-1168.
[7]	Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function[J]. Cell, 2004，116(2)：281-297.
[8]	Lim LP, Lau NC, Garrett-Engele P, et al. Microarray analysis shows that some microRNAs down regulate large numbers of target mRNAs[J]. Nature, 2005，433(7027)：769-773.
[9]	Dykxhoorn DM. MicroRNAs and metastasis: little RNAs go a long way[J]. Cancer Res, 2010，70(16)：6401-6406.
[10]	Calin GA, Croce CM. MicroRNA signatures in human cancers[J]. Nat Rev Cancer, 2006，6(11)：857-866.
[11]	Lovat F, Valeri N, Croce CM. Micro-RNAs in the pathogenesis of cancer[J]. Semin Oncol, 2011，38(6)：724-733.
[12]	Chen PS, Su JL, Hung MC. Dysregulation of microRNAs in cancer[J]. J Biomed Sci, 2012，19：90.
[13]	贾筱琴，缪俊俊，雍军，等．miR-148a对肝癌细胞株侵袭和迁移的抑制作用及机制[J]．中国癌症杂志，2014，24(6)：412-417.
[14]	Chen Y, Song Y, Wang Z, et al. Altered expression of MiR-148a and MiR-152 in gastrointestinal cancers and its clinical significance[J]. J Gastrointest Surg, 2010，14(7)：1170-1179.
[15]	Hummel R, Watson DI, Smith C, et al. Mir-148a improves response to chemotherapy in sensitive and resis-tant oesophageal adenocarcinoma and squamous cell carcinoma cells[J]. J Gastrointest Surg, 2011，15(3)：429-438.
[16]	Zhang H, Li Y, Huang Q, et al. MiR-148a promotes apoptosis by targeting Bcl-2 in colorectal cancer[J]. Cell Death Differ, 2011，18(11)：1702-1710.
[17]	Takahashi M, Cuatrecasas M, Balaguer F, et al. The clinical significance of MiR-148a as a predictive biomarker in patients with advanced colorectal cancer[J]. PLoS One, 2012，7(10)：e46684.
[18]	Korst RJ, Rusch VW, Venkatraman E, et al. Proposed revision of the staging classification for esophageal cancer[J]. J Thorac Cardiovasc Surg, 1998；115(3)：660- 669.
[19]	Hamilton SR, Aaltonen LA. Tumours of the digestive system[M]//Pathology and Genetics, World Health Organization Classification of Tumours. Lyon：IARC Press, 2000：10-25.
[20]	Greene FL, Page DL, Fleming ID, et al. AJCC cancer staging handbook[M]. 6th ed. New York: Springer-Verlag, 2002：91-98.
[21]	Fujita Y, Kojima K, Ohhashi R, et al. MiR-148a attenuates paclitaxel resistance of hormone-refractory, drug-resistant prostate cancer PC3 cells by regulating MSK1 expression[J]. J Biol Chem, 2010，285(25)：19076-19084.
[22]	Murata T, Takayama K, Katayama S, et al. miR-148a is an androgen-responsive microRNA that promotes LNCaP prostate cell growth by repressing its target CAND1 expression[J]. Prostate Cancer Prostatic Dis, 2010，13(4)：356-361.
[23]	邱光庭，王遂函，李大鹏，等．微小RNA-148a对胃癌细胞MKN45增殖能力的影响及机制研究[J]．中华胃肠外科杂志，2014，17(10)：1036-1039.
[24]	Bofill-De Ros X, Gironella M, Fillat C. miR-148a- and miR-216a-regulated oncolytic adenoviruses targeting pancreatic tumors attenuate tissue damage without perturbation of miRNA activity[J]. Mol Ther, 2014，22(9)：1665-1677.
[25]	Tao S, He H, Chen Q, et al. GPER mediated estradiol reduces miR-148a to promote HLA-G expression in breast cancer[J]. Biochem Biophys Res Commun, 2014，451(1)：74-78.
[26]	Zhou X, Zhao F, Wang ZN, et al. Altered expression of miR-152 and miR-148a in ovarian cancer is related to cell proliferation[J]. Oncol Rep, 2012，27(2)：447-454.

指标		总例数	miR-148a表达(例)		低表达率(%)	χ ²值	P值
指标		总例数	低表达	高表达	低表达率(%)	χ ²值	P值
性别		?	?	?	?	0.230	0.632
?	男性	56	23	33	41.1	?	?
?	女性	19	9	10	47.4	?	?
年龄(岁)		?	?	?	?	0.020	0.888
?	<50	17	7	10	41.2	?	?
?	≥50	58	25	33	43.1	?	?
肿瘤直径(cm)		?	?	?	?	0.523	0.770
?	<3	12	4	8	33.3	?	?
?	3～5	40	18	22	45.0	?	?
?	>5	23	10	13	43.5	?	?
分化程度		?	?	?	?	0.461	0.794
?	高	12	5	7	41.7	?	?
?	中	39	18	21	46.2	?	?
?	低	24	9	15	37.5	?	?
浸润深度		?	?	?	?	8.149	0.017
?	T₁	10	2	8	20.0	?	?
?	T₂	25	7	18	28.0	?	?
?	T₃	40	23	17	57.5	?	?
淋巴结转移		?	?	?	?	4.151	0.042
?	N₀	36	11	25	30.6	?	?
?	N₁	39	21	18	53.8	?	?
病理分期		?	?	?	?	6.474	0.039
?	Ⅰ	9	2	7	22.2	?	?
?	Ⅱ	38	13	25	34.2	?	?
?	Ⅲ	28	17	11	60.7	?	?

指标		总例数	miR-148a表达(例)		低表达率(%)	χ ²值	P值
指标		总例数	低表达	高表达	低表达率(%)	χ ²值	P值
性别		?	?	?	?	0.230	0.632
?	男性	56	23	33	41.1	?	?
?	女性	19	9	10	47.4	?	?
年龄(岁)		?	?	?	?	0.020	0.888
?	<50	17	7	10	41.2	?	?
?	≥50	58	25	33	43.1	?	?
肿瘤直径(cm)		?	?	?	?	0.523	0.770
?	<3	12	4	8	33.3	?	?
?	3～5	40	18	22	45.0	?	?
?	>5	23	10	13	43.5	?	?
分化程度		?	?	?	?	0.461	0.794
?	高	12	5	7	41.7	?	?
?	中	39	18	21	46.2	?	?
?	低	24	9	15	37.5	?	?
浸润深度		?	?	?	?	8.149	0.017
?	T₁	10	2	8	20.0	?	?
?	T₂	25	7	18	28.0	?	?
?	T₃	40	23	17	57.5	?	?
淋巴结转移		?	?	?	?	4.151	0.042
?	N₀	36	11	25	30.6	?	?
?	N₁	39	21	18	53.8	?	?
病理分期		?	?	?	?	6.474	0.039
?	Ⅰ	9	2	7	22.2	?	?
?	Ⅱ	38	13	25	34.2	?	?
?	Ⅲ	28	17	11	60.7	?	?

指标	χ ²值	单因素分析(P值)	多因素分析
指标	χ ²值	单因素分析(P值)	P值	OR值	95% CI
性别	0.789	0.374	0.567	1.218	0.620～2.392
年龄	1.065	0.302	0.723	1.134	0.567～2.268
肿瘤直径	0.333	0.847	0.768	1.066	0.696～1.632
分化程度	0.205	0.903	0.114	1.407	0.922～2.149
浸润深度	18.288	<0.001	0.044	1.685	1.015～2.799
淋巴结转移	14.285	<0.001	0.007	2.483	1.285～4.796
miR-148a表达	9.136	0.003	0.237	1.448	0.784～2.674

指标	χ ²值	单因素分析(P值)	多因素分析
指标	χ ²值	单因素分析(P值)	P值	OR值	95% CI
性别	0.789	0.374	0.567	1.218	0.620～2.392
年龄	1.065	0.302	0.723	1.134	0.567～2.268
肿瘤直径	0.333	0.847	0.768	1.066	0.696～1.632
分化程度	0.205	0.903	0.114	1.407	0.922～2.149
浸润深度	18.288	<0.001	0.044	1.685	1.015～2.799
淋巴结转移	14.285	<0.001	0.007	2.483	1.285～4.796
miR-148a表达	9.136	0.003	0.237	1.448	0.784～2.674

Please choose a citation manager

Content to export