Expression of abnormal spindle-like microcephaly associated protein in non-small cell lung cancer and its clinical significance

doi:10.3877/cma.j.issn.1674-6880.2020.03.004

Abstract

Abstract:

Objective

To investigate the expression of abnormal spindle-like microcephaly associated protein (ASPM) in tumor and paracancerous tissues of patients with non-small cell lung cancer (NSCLC) and its relationship with their clinicopathological parameters and prognosis.

Methods

Paraffin samples including tumor and paracancerous tissues were collected from 175 NSCLC patients who had been followed up for 5 years and the expression of ASPM was detected by immunohistochemical staining in each tissue. The age, sex ratio, differentiation ratio, smoking history, pathological type, tumor size, lymph node metastasis and TNM staging ratio were compared among patients with different ASPM expression levels. The Kaplan-Meier survival curve was drawn and the 5-year overall survival rate of NSCLC patients was compared by the log-rank test. The Cox regression model was used to analyze the risk factors for the prognosis of NSCLC patients.

Results

The immunohistochemical staining revealed that 64.57% (113 / 175) of tumor tissue samples showed high expression of ASPM, while only 22.29% (39 / 175) of adjacent tissues showed high expression of ASPM. The high expression ratio of ASPM in tumor tissues of NSCLC patients was significantly higher than that in adjacent tissues ( χ² = 63.683, P < 0.001). The 175 NSCLC patients were divided into an ASPM low expression group (n = 62) and an ASPM high expression group (n = 113) according to the staining results of tumor tissue samples. The tumor size ( χ² = 5.060, P = 0.024), lymph node metastasis ( χ² = 3.998, P = 0.046) and TNM staging ( χ² = 5.427, P = 0.020) were statistically significantly different between these two groups. The Kaplan-Meier survival curve showed that the 5-year overall survival rate of NSCLC patients in the ASPM low expression group was significantly better than that in the ASPM high expression group ( χ² = 5.040, P = 0.025). The tumor size, lymph node metastasis, TNM stage and ASPM expression were included in the Cox regression analysis, and the result showed the TNM stage [hazard ratio (HR) = 3.883, 95% confidence interval (CI) (1.616, 9.330), P = 0.005] and ASPM expression [HR = 3.845, 95%CI (1.795, 8.236), P = 0.008] were risk factors for the prognosis of NSCLC patients.

Conclusion

ASPM is highly expressed in the tumor tissues of NSCLC patients, and its expression is a risk factor for their prognosis.

Key words: Abnormal spindle-like microcephaly associated protein, Carcinoma, non-small cell lung, Immunohistochemistry staining, Prognosis

Rui Zhang, Yafang Shen, Xiaoxia An, Shuang Lin. Expression of abnormal spindle-like microcephaly associated protein in non-small cell lung cancer and its clinical significance[J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2020, 13(03): 176-180.

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Figures/Tables 4

References 21

1	Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019[J]. CA Cancer J Clin, 2019, 69 (1): 7-34.
2	宁洪叶，蒋贤高，施伎蝉，等. 结核分枝杆菌感染对非小细胞肺癌患者调节性免疫细胞的负向调节作用[J/CD]. 中华危重症医学杂志（电子版），2019，12(4):240-244. URL
3	Souquet PJ, Couraud S. Immune checkpoint inhibitors: a game changer for metastatic non-small-cell lung cancer[J]. Lancet Oncol, 2019, 20 (10): 1334-1335.
4	Johnson MB, Sun X, Kodani A, et al. Aspm knockout ferret reveals an evolutionary mechanism governing cerebral cortical size[J]. Nature, 2018, 556 (7701): 370-375.
5	喻昊骏. TPX2与ASPM在前列腺癌中表达的相关性及临床意义[D]. 广州：广州医科大学，2018.
6	Shi Z, Xiao Z, Hu L, et al. The genetic association between type 2 diabetic and hepatocellular carcinomas[J]. Ann Transl Med, 2020, 8 (6): 380.
7	Lin S, Zhang R, An X, et al. LncRNA HOXA-AS3 confers cisplatin resistance by interacting with HOXA3 in non-small-cell lung carcinoma cells[J]. Oncogenesis, 2019, 8 (11): 60.
8	Zhai S, Lin S, Lin Z, et al. eIF4EBP3 was downreg-ulated by methylation and acted as a tumor suppressor by targeting eIF4E / β-catenin in gastric cancer[J]. Gastric Cancer, 2020, 23 (3): 483-496.
9	李伟琴. 口腔鳞状细胞癌患者血清Cyfra 21-1和癌胚抗原含量检测的临床意义[J/CD]. 中华危重症医学杂志（电子版），2019，12(2):126-127. URL
10	Arbour KC, Riely GJ. Systemic therapy for locally advanced and metastatic non-small cell lung cancer: a review[J]. JAMA, 2019, 322 (8): 764-774.
11	张秀义，许浩然，孙亚东. 非小细胞肺癌组织Beclin1、LC3表达变化及其临床意义[J]. 山东医药，2018，58(48):66-69.
12	Jiang K, Rezabkova L, Hua S, et al. Microtubule minus-end regulation at spindle poles by an ASPM-katanin complex[J]. Nat Cell Biol, 2017, 19 (5): 480-492.
13	Gai M, Bianchi FT, Vagnoni C, et al. ASPM and CITK regulate spindle orientation by affecting the dynamics of astral microtubules[J]. EMBO Rep, 2017, 18 (10): 1870.
14	梁文涛. 胶质瘤中ASPM与MGMT表达及其临床意义[D]. 兰州：兰州大学，2015.
15	Timaner M, Shaked Y. Elucidating the roles of ASPM isoforms reveals a novel prognostic marker for pancreatic cancer[J]. J Pathol, 2019, 250 (2): 123-125.
16	Pai VC, Hsu CC, Chan TS, et al. ASPM promotes prostate cancer stemness and progression by augmenting Wnt-Dvl-3-β-catenin signaling[J]. Oncogene, 2019, 38 (8): 1340-1353.
17	Wang F, Li J, Liu J, et al. Controversial role of the possible oxyntic stem cell marker ASPM in gastric cancer[J]. J Pathol, 2017, 241 (4): 559-561.
18	Selamat SA, Chung BS, Girard L, et al. Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression[J]. Genome Res, 2012, 22 (7): 1197-1211.
19	Hou J, Aerts J, den Hamer B, et al. Gene expression-based classification of non-small cell lung carcinomas and survival prediction[J]. PLoS One, 2010, 5 (4): e10312.
20	Okayama H, Kohno T, Ishii Y, et al. Identification of genes upregulated in ALK-positive and EGFR / KRAS / ALK-negative lung adenocarcinomas[J]. Cancer Res, 2012, 72 (1): 100-111.
21	Gyorffy B, Surowiak P, Budczies J, et al. Online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-small-cell lung cancer[J]. PLoS One, 2013, 8 (12): e82241.

组别	例数	年龄		性别		分化程度		吸烟史
组别	例数	≤ 50岁	> 50岁	男	女	中、高分化	未分化及低分化	无	有
ASPM低表达组	62	34	28	26	36	27	35	28	34
ASPM高表达组	113	56	57	41	72	61	52	39	74
χ²值	?	0.447		0.541		1.743		1.921
P值	?	0.504		0.462		0.187		0.166
组别	例数	病理类型		肿瘤大小		淋巴结转移		TNM分期
组别	例数	腺癌	鳞癌	≤ 2 cm	> 2 cm	无	有	Ⅰ期	Ⅱ ~ Ⅲ期
ASPM低表达组	62	37	25	39	23	41	21	41	21
ASPM高表达组	113	55	58	51	62	57	56	54	59
χ²值	?	1.945		5.060		3.998		5.427
P值	?	0.163		0.024		0.046		0.020

组别	例数	年龄		性别		分化程度		吸烟史
组别	例数	≤ 50岁	> 50岁	男	女	中、高分化	未分化及低分化	无	有
ASPM低表达组	62	34	28	26	36	27	35	28	34
ASPM高表达组	113	56	57	41	72	61	52	39	74
χ²值	?	0.447		0.541		1.743		1.921
P值	?	0.504		0.462		0.187		0.166
组别	例数	病理类型		肿瘤大小		淋巴结转移		TNM分期
组别	例数	腺癌	鳞癌	≤ 2 cm	> 2 cm	无	有	Ⅰ期	Ⅱ ~ Ⅲ期
ASPM低表达组	62	37	25	39	23	41	21	41	21
ASPM高表达组	113	55	58	51	62	57	56	54	59
χ²值	?	1.945		5.060		3.998		5.427
P值	?	0.163		0.024		0.046		0.020

危险因素	回归系数	标准误	Wald值	P值	HR值	95%CI
肿瘤大小	0.119	0.221	6.721	0.209	2.409	0.322 ~ 2.391
淋巴结转移	0.340	0.261	3.567	0.712	2.865	1.436 ~ 5.716
TNM分期	0.521	0.042	12.761	0.005	3.883	1.616 ~ 9.330
ASPM表达	0.385	0.176	15.235	0.008	3.845	1.795 ~ 8.236

危险因素	回归系数	标准误	Wald值	P值	HR值	95%CI
肿瘤大小	0.119	0.221	6.721	0.209	2.409	0.322 ~ 2.391
淋巴结转移	0.340	0.261	3.567	0.712	2.865	1.436 ~ 5.716
TNM分期	0.521	0.042	12.761	0.005	3.883	1.616 ~ 9.330
ASPM表达	0.385	0.176	15.235	0.008	3.845	1.795 ~ 8.236

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