Expression of lymphoid enhancer factor-1 in pancreatic ductal adenocarcinoma and its effect on prognosis

doi:10.3760/cma.j.cn371439-20201111-00119

Abstract

Abstract:

Objective To investigate the expression of lymphoid enhancement factor-1 (LEF-1) in Wnt signaling pathway in pancreatic ductal adenocarcinoma (PDAC) and its significance. Methods The relative expressions of LEF-1 mRNA in human PDAC cell line PANC-1 and normal pancreatic ductal epithelial cell line HPDE6 were detected by fluorescence quantitative PCR. A total of 45 pancreatic cancer tissue specimens and their corresponding paracancerous tissue specimens were collected from the Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Xinjiang Medical University from June 2012 to December 2013. The expressions of LEF-1 in the cancer tissues and paracancerous tissues were detected by immunohistochemistry, and the relationships between LEF-1 expression and clinicopathological characteristics and prognosis of patients were analyzed. Results Fluorescence quantitative PCR showed that the relative expression level of LEF-1 mRNA in PANC-1 cell line was significantly higher than that in HPDE-6 cell line (2.895±0.485 vs. 1.006±0.126, t=3.056, P<0.001). Immunohistochemical results showed that LEF-1 was highly expressed in 33 cases (73.3%) of cancer tissues, which was higher than that in 12 cases (26.7%) of adjacent tissues, and there was a statistically significant difference (χ²=14.815, P<0.001). LEF-1 expression was correlated with preoperative carbohydrate antigen (CA) 19-9 level (P<0.001) and local lymph node metastasis (P=0.041). Survival analysis showed that the median overall survival (OS) was 22.0 months in patients with PDAC, 19.0 months in patients with high LEF-1 expression (n=33), 31.0 months in patients with low LEF-1 expression (n=12), and there was a statistically significant difference (χ ²=5.554, P=0.018). Univariate Cox regression analysis showed that age (HR=1.962, 95%CI: 1.043-3.692, P=0.037), LEF-1 (HR=2.253, 95%CI: 1.097-4.630, P=0.027), and CA19-9 (HR=2.667, 95%CI: 1.258-5.656, P=0.011) were associated with OS. Multivariate Cox regression analysis showed that CA19-9 (HR=6.431, 95%CI: 1.078-38.382, P=0.041), CA125 (HR=0.151, 95%CI: 0.027-0.839, P=0.031), primary tumor size (HR=8.364, 95%CI: 1.925-36.335, P=0.005), LEF-1 (HR=2.281, 95%CI: 1.025-5.075, P=0.043) were independent risk factors affecting the prognosis of PDAC patients. Conclusion LEF-1 expression is up-regulated in PDAC tissues, which is positively correlated with preoperative CA19-9 level and local lymph node metastasis, and is an independent prognostic factor in patients with PDAC.

Key words: Lymphoid enhancer-binding factor 1, Wnt signaling pathway, Pancreatic neoplasms, Prognosis

Li Keke, Kong Panpan, Yi Chao, Wang Xiyan, Yan Dong. Expression of lymphoid enhancer factor-1 in pancreatic ductal adenocarcinoma and its effect on prognosis[J]. Journal of International Oncology, 2021, 48(10): 608-613.

Figures/Tables 5

References 14

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临床病理特征	例数	LEF-1		χ²值	P值	临床病理特征	例数	LEF-1		χ²值	P值
临床病理特征	例数	高表达	低表达	χ²值	P值	临床病理特征	例数	高表达	低表达	χ²值	P值
性别						肿瘤大小(cm)
男性	27	20	7	0.019	0.891	≤2.0	11	8	3
女性	18	13	5			2.1~4.0	22	18	4	―	0.379
年龄(岁)						>4.0	12	7	5
≤60	24	17	7	0.164	0.685	肿瘤浸润情况
>60	21	16	5			无浸润	24	16	8
BMI(kg/m²)						十二指肠黏膜层	2	2	0
<18.5	2	2	0			十二指肠黏膜下层	4	2	2	―	0.440
18.5~23.9	19	14	5	―	>0.999	十二指肠肌层	5	4	1
≥24.0	24	17	7			十二指肠浆膜层	10	9	1
糖尿病						局部淋巴结转移
无	37	29	8	―	0.181	无	18	10	8	―	0.041
有	8	4	4			有	27	23	4
术前总胆红素(μmol/L)						TNM分期
≤17.1	13	11	2	―	0.460	Ⅰa	2	1	1
>17.1	32	22	10			Ⅰb	14	9	5
术前直接胆红素(μmol/L)						Ⅱa	11	7	4	―	0.301
≤6.8	16	13	3	―	0.491	Ⅱb	17	15	2
>6.8	29	20	9			Ⅲ	1	1	0
术前CA19-9(U/ml)						肿瘤分化程度
≤40	12	4	8	―	<0.001	高分化	16	9	7
>40	33	29	4			中分化	14	13	1	―	0.089
术前CA125(U/ml)						低分化	15	11	4
≤35	37	26	11	―	0.419
>35	8	7	1

临床病理特征	HR值	95% CI	P值
性别	1.585	0.849~2.958	0.148
年龄	1.962	1.043~3.692	0.037
BMI	0.819	0.475~1.412	0.472
有无糖尿病	1.989	0.880~4.496	0.099
术前总胆红素	0.580	0.295~1.140	0.114
术前直接胆红素	0.615	0.321~1.176	0.142
CA19-9	2.667	1.258~5.656	0.011
CA125	0.801	0.369~1.739	0.575
原发肿瘤大小	1.242	0.855~1.804	0.254
原发肿瘤浸润情况	0.909	0.764~1.081	0.279
局部淋巴结转移	1.150	0.625~2.114	0.654
肿瘤分期	1.123	0.841~1.501	0.432
肿瘤分化	1.124	0.793~1.593	0.513
LEF-1	2.253	1.097~4.630	0.027

临床病理特征	β值	SE值	Wald值	HR值	95%CI	P值
CA19-9	1.861	0.911	4.170	6.431	1.078~38.382	0.041
CA125	-1.893	0.876	4.665	0.151	0.027~0.839	0.031
原发肿瘤大小	2.124	0.749	8.033	8.364	1.925~36.335	0.005
LEF-1	0.825	0.408	4.086	2.281	1.025~5.075	0.043

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