肺腺癌组织中IGF1R、Cezanne-1表达与EGFR基因突变的相关性分析

doi:10.3877/cma.j.issn.1674-6902.2020.03.007

目的

探讨肺腺癌组织中胰岛素样生长因子-1受体(IGF1R)、Cezanne-1表达与表皮生长因子受体(EGFR)基因突变情况，分析IGF1R、Cezanne-1表达与EGFR基因突变的相关性。

方法

选择2017年3月至2019月4月本医经病理确诊且得到明确肺腺癌肿瘤组织与癌旁组织的肺腺癌患者56例，将其纳入病例组；纳入同期在医院接受手术治疗并在术中获得病灶组织的51例肺部良性病变患者，将其作为对照组。对全部纳入的组织样本进行IGF1R、Cezanne-1表达与EGFR基因突变检查，比较各组IGF1R、Cezanne-1阳性表达与EGFR基因突变检出率；比较不同EGFR基因突变肺腺癌患者临床特征、IGF1R、Cezanne-1阳性检出率；分析IGF1R、Cezanne-1表达与EGFR基因突变的相关性。

结果

肺腺癌组织EGFR基因突变、IGF1R、Cezanne-1阳性检出率均高于癌旁组织及肺部良性病变组，差异有统计学意义(P<0.05)；EGFR基因突变的肺腺癌患者与其他未检出基因突变的肺腺癌患者的临床特征比较，差异均无统计学意义(P>0.05)，但较未检出EGFR基因突变的肺腺癌组织，检出基因突变的组织中IGF1R、Cezanne-1阳性检出率更高，差异有统计学意义(P<0.05)；IGF1R、Cezanne-1表达与EGFR基因突变之间均呈正相关(r>0，P<0.05)。

结论

肺腺癌组织内IGF1R、Cezanne-1多呈过表达，EGFR基因突变率较其他正常组织高，且这种IGF1R、Cezanne-1的过表达与EGFR基因突变明显相关。

关键词: 肺腺癌, IGF1R, Cezanne-1, EGFR基因突变, 相关性, 预测价

Objective

To analyze the correlation between the expression levels of insulin-like growth factor-1 receptor (IGF1R) and Cezanne-1 and the gene mutations of epidermal growth factor receptor (EGFR) in lung adenocarcinoma tissues.

Methods

Clear lung adenocarcinoma tissues and para-carcinoma tissues obtained from the 56 patients with lung adenocarcinoma who were pathologically diagnosed in our hospital from March 2017 to April 2019 were included in the case group, and lesion tissues from the 51 patients with benign pulmonary lesions who underwent surgical treatment during the same period were included in the control group. The expression levels of IGF1R and Cezanne-1 and EGFR gene mutations of all the included tissue samples were examined, and the detection rates of IGF1R and Cezanne-1 positive expression and EGFR gene mutations were compared between the two groups. The clinical features, the positive detection rates of IGF1R and Cezanne-1 expression of the lung adenocarcinoma patients with different EGFR gene mutations were compared. The correlation between the expression levels of IGF1R and Cezanne-1 and EGFR gene mutations was analyzed, too.

Results

The positive detection rates of EGFR gene mutations and the expression levels of IGF1R and Cezanne-1 in the lung adenocarcinoma tissues were higher than those of the para-carcinoma tissues and the benign pulmonary lesions (P<0.05). There was no statistical significant difference in the clinical features between the lung adenocarcinoma patients with EGFR gene mutations and the lung adenocarcinoma patients without gene mutations (P>0.05). However, compared with the lung adenocarcinoma tissues without EGFR gene mutations, the positive detection rates of IGF1R and Cezanne-1 expression in the tissues with gene mutations were higher (P<0.05). The IGF1R and Cezanne-1 expression had positive correlations with EGFR gene mutations (r>0, P<0.05).

Conclusion

The IGF1R and Cezanne-1 are over-expressed in the lung adenocarcinoma tissues, and the EGFR gene mutation rate is higher than that of other normal tissues. Moreover, the over-expression of IGF1R and Cezanne-1 is significantly related to EGFR gene mutations.

Key words: Lung adenocarcinoma, IGF1R, Cezanne-1, EGFR gene mutation, Correlation, Predictive value

表1 各组EGFR基因突变阳性检出率比较

组　别		例数	组织样本	EGFR基因突变阳性例数(例)	阳性率(%)
研究组		56	肺腺癌组织	32	57.14
			癌旁组织	6	10.71^ab
对照组		51	肺部良性组织	1	1.96
	χ²值		-	-	52.835
	P值		-	-	<0.001

表1 各组EGFR基因突变阳性检出率比较

组　别		例数	组织样本	EGFR基因突变阳性例数(例)	阳性率(%)
研究组		56	肺腺癌组织	32	57.14
			癌旁组织	6	10.71^ab
对照组		51	肺部良性组织	1	1.96
	χ²值		-	-	52.835
	P值		-	-	<0.001

表2 研究组患者EGFR突变患者与未突变患者的临床特征比较

肺腺癌EGFR基因突变情况		例数	性别(例)		年龄(岁)	吸烟史(例)		TNM分期(例)
肺腺癌EGFR基因突变情况		例数	男性	女性	年龄(岁)	有	无	Ⅰ期	Ⅱ期	Ⅲ期	Ⅳ期
突变患者		32	21	11	52.47±7.11	20	12	2	6	17	7
未突变患者		24	15	9	49.09±11.02	11	13	1	7	12	4
统计值		-	0.058^a		1.393^b	1.542^a		0.650^c
	P值	-	0.809^a		0.169^b	0.214^a		0.516^c

表2 研究组患者EGFR突变患者与未突变患者的临床特征比较

肺腺癌EGFR基因突变情况		例数	性别(例)		年龄(岁)	吸烟史(例)		TNM分期(例)
肺腺癌EGFR基因突变情况		例数	男性	女性	年龄(岁)	有	无	Ⅰ期	Ⅱ期	Ⅲ期	Ⅳ期
突变患者		32	21	11	52.47±7.11	20	12	2	6	17	7
未突变患者		24	15	9	49.09±11.02	11	13	1	7	12	4
统计值		-	0.058^a		1.393^b	1.542^a		0.650^c
	P值	-	0.809^a		0.169^b	0.214^a		0.516^c

表3 IGF1R、Cezanne-1阳性表达检出率比较

组　别		例数	组织样本	IGF1R		Cezanne-1
组　别		例数	组织样本	例数	阳性率(%)	例数	阳性率(%)
研究组		56	肺腺癌组织	36	64.29^ab	38	67.86^ab
			癌旁组织	8	14.29	10	17.86
对照组		51	肺部良性组织	3	5.88	4	7.84
	χ²值		-	53.167		51.997
	P值		-	<0.001		<0.001

表3 IGF1R、Cezanne-1阳性表达检出率比较

组　别		例数	组织样本	IGF1R		Cezanne-1
组　别		例数	组织样本	例数	阳性率(%)	例数	阳性率(%)
研究组		56	肺腺癌组织	36	64.29^ab	38	67.86^ab
			癌旁组织	8	14.29	10	17.86
对照组		51	肺部良性组织	3	5.88	4	7.84
	χ²值		-	53.167		51.997
	P值		-	<0.001		<0.001

表4 不同EGFR基因突变肺腺癌组织中IGF1R、Cezanne-1阳性检出率比较

变　量		例数	IGF1R		Cazanne-1
变　量		例数	例数	阳性率(%)	例数	阳性率(%)
EGFR基因突变患者		32	30	93.75	28	87.50
EGFR基因未突变		24	6	25.00	10	41.67
	χ²值	-	28.233		13.209
	P值	-	<0.001		<0.001

表4 不同EGFR基因突变肺腺癌组织中IGF1R、Cezanne-1阳性检出率比较

变　量		例数	IGF1R		Cazanne-1
变　量		例数	例数	阳性率(%)	例数	阳性率(%)
EGFR基因突变患者		32	30	93.75	28	87.50
EGFR基因未突变		24	6	25.00	10	41.67
	χ²值	-	28.233		13.209
	P值	-	<0.001		<0.001

表5 肺腺癌组织中IGF1R、Cezanne-1表达与EGFR基因突变的相关性分析结果r(P)

指　标	EGFR基因突变	IGF1R	Cezanne-1
EGFR基因突变	-	0.731(<0.001)	0.515(<0.001)
IGF1R	0.731(<0.001)	-	0.784(<0.001)
Cezanne-1	0.515(<0.001)	0.784(<0.001)	-

表5 肺腺癌组织中IGF1R、Cezanne-1表达与EGFR基因突变的相关性分析结果r(P)

指　标	EGFR基因突变	IGF1R	Cezanne-1
EGFR基因突变	-	0.731(<0.001)	0.515(<0.001)
IGF1R	0.731(<0.001)	-	0.784(<0.001)
Cezanne-1	0.515(<0.001)	0.784(<0.001)	-

1	赛亚飞，高美丽，金发光，等. 血清肿瘤标志物CEA、CA125、CYFRA21-1在支气管肺癌诊断、病理类型及TNM分期中的价值分析[J/CD]. 中华肺部疾病杂志(电子版), 2019, 12(1): 39-42.
2	Zhuo P, Pan LF, Niu ZQ, et al. Identification of microRNAs as potential biomarkers for lung adenocarcinoma using integrating genomics analysis[J]. Oncotarget, 2017, 8(38): 64143.
3	Thumallapally N, Yu H, Farhan M, et al. Concomitant Presence of EGFR and ALK Fusion Gene Mutation in Adenocarcinoma of Lung: A Case Report and Review of the Literature[J]. J Pharm Pract, 2017, 31(3): 089719001770475.
4	Obeidat N, Awidi A, Ababneh N, et al. Frequency of epidermal growth factor receptor mutations in Jordanian lung adenocarcinoma patients at diagnosis[J]. J Cancer Res Ther, 2016, 12(2): 616-619.
5	Inoue T, Matsumura Y, Araki O, et al. Epidermal Growth Factor Receptor Gene Mutation in Pleural Lavage Cytology Findings of Primary Lung Adenocarcinoma Cases[J]. Ann Thorac Cardiovasc Surg, 2017, 24(1): 1-5.
6	杨　柳. 肺腺癌EGFR基因突变与血清肿瘤标志物的关系[D]. 郑州大学，2014: 12-35.
7	Li H, Cao J, Zhang X, et al. Correlation between status of epidermal growth factor receptor mutation and distant metastases of lung adenocarcinoma upon initial diagnosis based on 1063 patients in China[J]. Clin Exp Metastasis, 2017, 34(1): 63-71.
8	Humar M, Kern I, Vlacic G, et al. Insulin-like Growth Factor 1 Receptor Expression in Advanced Non-small-cell Lung Cancer and its Impact on Overall Survival[J]. Radiol Oncol, 2017, 51(2): 195-202.
9	Nurwidya F, Andarini S, Takahashi F, et al. Implications of Insulin-like Growth Factor 1 Receptor Activation in Lung Cancer[J]. Malays J Med Sci, 2016, 23(3): 9-21.
10	Guo XF, Zhu XF, Cao HY, et al. A bispecific enediyne-energized fusion protein targeting both epidermal growth factor receptor and insulin-like growth factor 1 receptor showing enhanced antitumor efficacy against non-small cell lung cancer[J]. Oncotarget, 2017, 8(16): 27286-27299.
11	崔丽萱. 胰岛素样生长因子受体-1与cezanne-1在肺腺癌中的预后作用分析[D]. 山东大学，2017: 23-45.
12	王　嘉，吴　楠，郑庆锋，等. 国际肺癌研究会2007年版肺癌分期方案的应用[J]. 北京大学学报(医学版), 2009, 41(4): 442-446.
13	Lengerich BV, Agnew C, Puchner EM, et al. EGF and NRG induce phosphorylation of HER3/ERBB3 by EGFR using distinct oligomeric mechanisms[J]. Proceedings of the National Academy of Sciences, 2017, 114(14): E2836-E2845.
14	Stricker S, Rauschenberger V, Schambony A. ROR-Family Receptor Tyrosine Kinases[J]. Curr Top Dev Biol, 2017, 123: 105-142.
15	Bazzani L, Donnini S, Finetti F, et al. PGE2/EP3/SRC signaling induces EGFR nuclear translocation and growth through EGFR ligands release in lung adenocarcinoma cells[J]. Oncotarget, 2017, 8(19): 31270-31287.
16	张　莹，王　哲，杨向红. 辽宁沈阳地区非小细胞肺癌EGFR基因突变分析[J]. 现代肿瘤医学，2018, 26(26): 25-39.
17	Sharma SV, Bell DW, Settleman J, et al. Epidermal growth factor receptor mutations in lung cancer[J]. Nat Rev Cancer, 2007, 7(3): 169-181.
18	陈天才，蒋　玮，曾爱屏，等. EGFR敏感突变型NSCLC患者血清CEA水平对靶向治疗疗效预测价值分析[J]. 中华肿瘤防治杂志，2018, 25(12): 877-882.
19	王　娜，郑　清，孙成铭，等. 非小细胞肺癌EGFR基因突变的表现及其与肿瘤标记物的相关性[J]. 现代肿瘤医学，2016, 24(19): 3053-3056.
20	Yu J, Wang L, Zhang T, et al. Co-expression of β-arrestin1 and NF-кB is associated with cancer progression and poor prognosis in lung adenocarcinoma[J]. Tumor Biol, 2015, 36(8): 6551-6558.
21	Gabriela C, Lobato SL, Imad T, et al. Abstract 58: Metformin impacts IGF-1R/Akt signaling and energy metabolism in lung adenocarcinoma[J]. Cancer Res, 2016, 76(14 Supplement): 58-58.
22	Baumgarten SC, Marah A, Chemyong K, et al. IGF1R Expression in Ovarian Granulosa Cells Is Essential for Steroidogenesis, Follicle Survival, and Fertility in Female Mice[J]. Endocrinology, 2017, 158(7): 2309-2318.
23	Solomon-Zemler R, Sarfstein R, Werner H. Nuclear insulin-like growth factor-1 receptor (IGF1R) displays proliferative and regulatory activities in non-malignant cells[J]. PLoS ONE, 2017, 12(9): e0185164.
24	Al-Saad S, Richardsen E, Kilvaer TK, et al. The impact of MET, IGF-1, IGF1R expression and EGFR mutations on survival of patients with non-small-cell lung cancer[J]. Plos One, 2017, 12(7): e0181527.
25	Komander D, Clague MJ, Urbé S. Breaking the chains: structure and function of the deubiquitinases[J]. Nat Rev Mol Cell Biol, 2009, 10(8): 550-563.
26	梁超超，程梦华，刘石娟. 去泛素化酶活性的调控[J]. 中国生物化学与分子生物学报，2018, 34(1): 38-44.
27	Pang Z, Cui L, Ding N, et al. Expressions of insulin-like growth factor receptor-1 and cezanne-1 in lung adenocarcinoma[J]. Med Oncol, 2017, 34(5): 78.
28	李启荣，师永红. 缺氧诱导因子1降解-泛素化研究进展[J]. 中华肿瘤防治杂志，2013, 20(17): 88-91.
29	Moniz S, Bandarra D, Biddlestone J, et al. Cezanne regulates E2F1-dependent HIF2α expression[J]. J Cell Sci, 2015, 128(16): 3082-3093.
30	Pareja F, Ferraro DA, Rubin C, et al. Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression[J]. Oncogene, 2012, 31(43): 4599-4608.

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Correlation between expression levels of insulin-like growth factor-1 receptor and Cezanne-1 and epidermal growth factor receptor gene mutations in lung adenocarcinoma tissues

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Correlation between expression levels of insulin-like growth factor-1 receptor and Cezanne-1 and epidermal growth factor receptor gene mutations in lung adenocarcinoma tissues