Expression of TPX2 in kidney renal clear cell carcinoma and its clinical significance

doi:10.3760/cma.j.cn371439-20230113-00042

Abstract

Abstract:

Objective To analyze the expression of targeting protein for Xklp2 （TPX2） in kidney renal clear cell carcinoma （KIRC） and its clinical significance. Methods The postoperative tissue samples of 54 patients with KIRC admitted to the Department of Urology， the First Affiliated Hospital of Bengbu Medical College from July 2017 to June 2019 were collected. Immunohistochemistry was used to detect the protein expression of TPX2 in renal carcinoma and paracancerous tissues. The difference of TPX2 mRNA expression between KIRC tissues and normal tissues was analyzed by using the TIMER database， which verified the immunohistochemical results. The UALCAN database and the Kaplan-Meier plotter database were used to analyze the relationship between TPX2 mRNA expression and clinical stage， molecular subtypes， lymph node metastasis， and prognosis of patients with KIRC. The protein interaction network was constructed by STRING database to obtain TPX2-related proteins， and the genes corresponding to the related proteins were enriched for the KEGG pathway. The relationship between TPX2 expression and immune cell infiltration and the immune checkpoint was studied by using the TIMER database. Results Immunohistochemical results showed that the positive expression rate of TPX2 protein was 48.15% （26/54） in cancer tissues， which was higher than that in paracancerous tissues （20.37%，11/54）（χ²=9.25， P=0.002）. The results of bioinformatics analysis showed that TPX2 mRNA expression was significantly up-regulated in KIRC [cancer tissue: 1.89 （1.49， 2.42）， normal tissue: 0.35 （0.24， 0.57）， U=2 297.00， P<0.001]. The expression of TPX2 mRNA was related to the clinical stage （χ²=34.36， P<0.001）， molecular subtypes （χ²=30.15， P<0.001）， and lymph node metastasis status （χ²=27.21， P<0.001） of KIRC patients. The 5-year survival rate （53.80%） in patients with high TPX2 expression was lower than that in patients with low TPX2 expression （74.40%， χ²=18.87， P<0.001）. STRING database protein interaction network construction obtained 20 TPX2-related proteins， and the genes corresponding to the related proteins were enriched in the cell cycle. The expression of TPX2 was positively correlated with B cells （r=0.30， P<0.001）， CD8⁺ T cells （r=0.23， P<0.001）， CD4⁺ T cells （r=0.18， P<0.001）， macrophages （r=0.20， P<0.001）， neutrophils （r=0.31， P<0.001）， dendritic cells （r=0.39， P<0.001） infiltration and most of its biomarkers （all P<0.05）. It was positively correlated with immune checkpoint PD-1 （r=0.31， P<0.001） and CTLA-4 （r=0.27， P<0.001）， but not correlated with PD-L1 （r=0.07， P=0.146）. Conclusion TPX2 is highly expressed in KIRC and is closely associated with poor prognosis. It is expected to be a new therapeutic target for KIRC.

Key words: Carcinoma, renal cell, Tumor escape, TPX2

Li Jun, Xue Sheng, Wang Weijie, Tao Run, Zhang Jiajun. Expression of TPX2 in kidney renal clear cell carcinoma and its clinical significance[J]. Journal of International Oncology, 2023, 50(4): 214-219.

Figures/Tables 6

References 14

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临床病理特征	TPX2表达量	χ²值	P值
临床分期
正常组织	0.35（0.24，0.56）
Ⅰ期	1.77（1.41，2.12）^a
Ⅱ期	1.74（1.33，2.30）^a	34.36	<0.001
Ⅲ期	2.03（1.60，2.56）^ab
Ⅳ期	2.57（1.83，3.22）^abcd
分子亚型
正常组织	0.35（0.24，0.56）
ccA亚型	1.82（1.45，2.30）^a	30.15	<0.001
ccB亚型	2.58（1.85，3.19）^ab
淋巴结转移状态
正常组织	0.35（0.24，0.56）
N₀	1.90（1.51，2.44）^a	27.21	<0.001
N₁	3.04（2.33，3.98）^ab

免疫细胞生物标志物	r值	P值
B细胞
CD19	0.27	<0.001
CD79A	0.22	<0.001
CD8⁺ T细胞
CD8A	0.34	<0.001
CD8B	0.30	<0.001
CD4⁺ T细胞
CD4	0.38	<0.001
M1巨噬细胞
NOS2	0.05	0.241
IRF5	0.22	<0.001
PTGS2	0.13	0.002
M2巨噬细胞
CD163	0.32	<0.001
VSIG4	0.34	<0.001
MS4A4A	0.31	<0.001
中性粒细胞
CEACAM8	-0.03	0.569
ITGAM	0.31	<0.001
CCR7	0.28	<0.001
树突状细胞
HLA-DPB1	0.23	<0.001
HLA-DQB1	0.09	0.035
HLA-DRA	0.26	<0.001
HLA-DPA1	0.28	<0.001
CD1C	0.08	0.061
NRP1	0.13	0.003
ITGAX	0.24	<0.001

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