Influence of Gli2 expression on liver neoplasms development and survival prognosis

doi:10.3877/cma.j.issn.1674-0793.2016.03.003

Abstract

Abstract:

Objective

To explore the expression of transcription factor Gli2 of Hedgehog (Hh) signaling pathway in human hepatocellular carcinoma (HCC) and its correlation with prognosis.

Methods

Immunohistochemistry was used for detection of Gli2 protein in sixty-eight pairs of HCC tissues and 20 samples of normal liver tissue from patients with liver hemangiomas. The correlation between Gli2 expression and clinicopathologic characteristics and prognosis were analyzed.

Results

The expression of Gli2 in HCC tissues (63.2%) was significantly higher than in paraneoplastic liver tissues (11.8%) and normal liver tissue (10.0%) (χ²=38.431、17528, all P<0.01). The expression level of Gli2 was significantly correlated with tumor differentiation, encapsulation, vascular invasion, early recurrence, and intrahepatic metastasis (P<0.05). The overall survival (OS) and disease free survival (DFS) rate of the patients with high Gli2 expression was lower than that of the patients with low Gli2 expression (P<0.05). The Cox multivariate analysis demonstrated that among the factors analyzed, Gli2 expression was an independent prognostic factor for OS and DFS in HCC patients after a curative resection (HR=2.239, P<0.05; HR=1.917, P<0.05).

Conclusion

The abnormal expression of Gli2 is closely related to invasion and metastasis of HCC and it can be used as a marker to evaluate the postoperative prognosis for patients with HCC.

Key words: Liver neoplasms, Transcription factors, Immunohistochemistry, Prognosis

Yue Li, Yu Zhang, Liangqi Cao, Ping Xue, Yize Hu, Dawei Zhang. Influence of Gli2 expression on liver neoplasms development and survival prognosis[J]. Chinese Archives of General Surgery(Electronic Edition), 2016, 10(03): 174-178.

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Figures/Tables 5

References 15

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病理特征		Gli2表达水平		χ²值	P值
病理特征		高(43例)	低(25例)	χ²值	P值
性别		?	?	?	?
?	男	33	20	0.097	0.755
?	女	10	5	?	?
年龄（岁）		?	?	?	?
?	≤60	29	14	0.890	0.345
?	>60	14	11	?	?
肝炎病毒		?	?	?	?
?	HBV	35	23	0.698	0.403
?	HCV	2	0	?	?
?	未感染	6	2	?	?
AFP(μg/L)		?	?	?	?
?	≤200	20	8	1.374	0.241
?	>200	23	17	?	?
肝硬化		?	?	?	?
?	有	30	18	0.038	0.846
?	无	13	7	?	?
肿直径(cm)		?	?	?	?
?	≤5	28	13	1.136	0.286
?	>5	15	12	?	?
TNM分期		?	?	?	?
?	Ⅰ-Ⅱ	25	20	3.375	0.066
?	Ⅲ-Ⅳ	18	5	?	?
肿瘤分化		?	?	?	?
?	高	6	10	6.591	0.037 ^a
?	中	28	11	?	?
?	低	9	4	?	?
肿瘤数目		?	?	?	?
?	单发	32	22	1.784	0.182
?	多发	11	3	?	?
包膜		?	?	?	?
?	完整	11	15	7.930	0.005 ^a
?	无或不完整	32	10	?	?
血管侵犯		?	?	?	?
?	有	23	6	5.620	0.018 ^a
?	无	20	19	?	?
早期复发		?	?	?	?
?	有	25	8	4.324	0.038 ^a
?	无	18	17	?	?
肝内转移		?	?	?	?
?	有	16	5	4.997	0.025 ^a
?	无	17	20	?	?

病理特征		Gli2表达水平		χ²值	P值
病理特征		高(43例)	低(25例)	χ²值	P值
性别		?	?	?	?
?	男	33	20	0.097	0.755
?	女	10	5	?	?
年龄（岁）		?	?	?	?
?	≤60	29	14	0.890	0.345
?	>60	14	11	?	?
肝炎病毒		?	?	?	?
?	HBV	35	23	0.698	0.403
?	HCV	2	0	?	?
?	未感染	6	2	?	?
AFP(μg/L)		?	?	?	?
?	≤200	20	8	1.374	0.241
?	>200	23	17	?	?
肝硬化		?	?	?	?
?	有	30	18	0.038	0.846
?	无	13	7	?	?
肿直径(cm)		?	?	?	?
?	≤5	28	13	1.136	0.286
?	>5	15	12	?	?
TNM分期		?	?	?	?
?	Ⅰ-Ⅱ	25	20	3.375	0.066
?	Ⅲ-Ⅳ	18	5	?	?
肿瘤分化		?	?	?	?
?	高	6	10	6.591	0.037 ^a
?	中	28	11	?	?
?	低	9	4	?	?
肿瘤数目		?	?	?	?
?	单发	32	22	1.784	0.182
?	多发	11	3	?	?
包膜		?	?	?	?
?	完整	11	15	7.930	0.005 ^a
?	无或不完整	32	10	?	?
血管侵犯		?	?	?	?
?	有	23	6	5.620	0.018 ^a
?	无	20	19	?	?
早期复发		?	?	?	?
?	有	25	8	4.324	0.038 ^a
?	无	18	17	?	?
肝内转移		?	?	?	?
?	有	16	5	4.997	0.025 ^a
?	无	17	20	?	?

影响因素	P值
影响因素	总生存率	无瘤生存率
性别（男vs女）	0.564	0.867
年龄（≤ 60岁vs >60岁）	0.430	0.682
肝炎病毒（HBV vs HCV和未感染）	0.410	0.247
AFP（≤ 200 μg/L vs >200 μg/L）	0.909	0.626
肝硬化（无vs有）	0.313	0.551
肿瘤直径(≤ 5 cm vs >5 cm)	0.005 ^a	0.001 ^a
TNM分期（Ⅰ-Ⅱ vs Ⅲ-Ⅳ）	0.034 ^a	0.056
肿瘤分化（高-中vs低）	0.011 ^a	0.110
肿瘤数目（单发vs多发）	0.401	0.741
包膜（完整vs无或不完整）	0.011 ^a	0.009 ^a
血管侵犯（无vs有）	0.003 ^a	0.001 ^a
Gli2表达（低vs高）	0.005 ^a	0.017 ^a

影响因素	P值
影响因素	总生存率	无瘤生存率
性别（男vs女）	0.564	0.867
年龄（≤ 60岁vs >60岁）	0.430	0.682
肝炎病毒（HBV vs HCV和未感染）	0.410	0.247
AFP（≤ 200 μg/L vs >200 μg/L）	0.909	0.626
肝硬化（无vs有）	0.313	0.551
肿瘤直径(≤ 5 cm vs >5 cm)	0.005 ^a	0.001 ^a
TNM分期（Ⅰ-Ⅱ vs Ⅲ-Ⅳ）	0.034 ^a	0.056
肿瘤分化（高-中vs低）	0.011 ^a	0.110
肿瘤数目（单发vs多发）	0.401	0.741
包膜（完整vs无或不完整）	0.011 ^a	0.009 ^a
血管侵犯（无vs有）	0.003 ^a	0.001 ^a
Gli2表达（低vs高）	0.005 ^a	0.017 ^a

影响因素		P值	风险比	95%置信区间
影响因素		P值	风险比	下限	上限
总生存率		?	?	?	?
?	肿瘤大小	0.002^a	2.509	1.414	4.454
?	TNM分期	NS	-	?	?
?	肿瘤分化	NS	-	?	?
?	包膜	NS	-	?	?
?	血管侵犯	0.004^a	2.305	1.304	4.073
?	Gli2表达	0.007^a	2.239	1.244	4.028
无瘤生存率		?	?	?	?
?	肿瘤大小	NS	-	?	?
?	包膜	0.001^a	2.763	1.534	4.977
?	血管侵犯	0.002^a	2.516	1.397	4.533
?	Gli2表达	0.042^a	1.917	1.025	3.584

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