Relationship between overexpression of serum exosomal has_circ_0060937 and metastasis and poor prognosis of NSCLC

doi:10.3877/cma.j.issn.1674-6902.2023.04.008

Abstract

Abstract:

Objective

To investigate the relationship between serum exosomal has_circ_0060937 and metastasis and poor prognosis of non-small cell lung cancer (NSCLC).

Methods

From May 2017 to December 2021, 63 patients with NSCLC and 83 patients with benign pulmonary nodulestreated in our hospital were included as the study subjects. The expression level of serum exosomal has_circ_0060937 was detected by real-time fluorescence quantitative PCR, and the overall survival rate was followed up.

Results

The expression level of serum exosomal has_circ_0060937 in NSCLC group was significantly higher than that in benign pulmonary nodules group(P<0.001), which can be used to distinguish NSCLC group vs. benign pulmonary nodules group. The area under the subject operating characteristic curve (AUC) was 0.858(95%CI: 0.818~0.898) and NSCLC patients were stratiized according to the median expression level of serum exosomal has_circ_0060937, and the high expression subgroup had a higher risk of TNM staging, lymph node metastasis and distant metastasis >2 locations (P<0.05). Serum exosomal has_circ_0060937 expression level predicted that the AUC of NSCLC lymph node metastasis or distant metastasis >2 sites was 0.855(95%CI: 0.807~0.903) and 0.762(95%CI: 0.702~0.823), respectively. The subgroup with low expression of serum exosomal has_circ_0060937 had a longer overall survival prognosis (χ²=14.022, P<0.00). Cox regression analysis showed that serum exosomal has_circ_0060937 expression level (HR=1.375, P<0.001) was a significant independent predictor of adverse overall survival.

Conclusion

Serum exosomal has_circ_0060937 is expected to be a new reliable biomarker for predicting metastasis and poor prognosis of NSCLC.

Key words: Serum exosomal has_circ_0060937, Non-small cell lung cancer, Tumor metastasis, Poor prognosis

Chenglu Huang, Fei Liao, Xianping Liu, Zhiqiang Wang. Relationship between overexpression of serum exosomal has_circ_0060937 and metastasis and poor prognosis of NSCLC[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2023, 16(04): 490-494.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhfbjbzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-6902.2023.04.008

https://zhfbjbzz.cma-cmc.com.cn/EN/Y2023/V16/I04/490

Figures/Tables 4

References 23

1	王洪武，金发光. 晚期非小细胞肺癌多域整合治疗策略[J/CD]. 中华肺部疾病杂志(电子版), 2022, 15(4): 457-461.
2	Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249.
3	Wang M, Herbst RS, Boshoff C. Toward personalized treatment approaches for non-small-cell lung cancer[J]. Nature medicine, 2021, 27(8): 1345-1356.
4	吕　婷，刘东璞，盛延良，等. 外泌体在过敏性疾病中的研究进展[J]. 中国老年学杂志，2022, 42(20): 5152-5156.
5	柯双熬，赵胜男，刘　玉，等. 环状RNA翻译蛋白在癌症中的研究进展[J]. 生物工程学报，2022, 38(9): 3131-3140.
6	徐　昊，方梦蝶，李　超，等. 新型肿瘤靶标环状RNA的研究进展[J]. 中国医学科学院学报，2021, 43(3): 435-444.
7	李燕伶，陈　艳. 外泌体环状RNA在肺癌中的研究进展[J]. 国际遗传学杂志，2021, 44(4): 255-260.
8	Zhang J, Mao W, Chen Z, et al. Clinical Significance of has_circ_0060937 in Bone Metastasis of NSCLC[J]. Int J Gen Med, 2020, 13: 1115-1121.
9	Xi J, Xi Y, Zhang Z, et al. Hsa_circ_0060937 accelerates non-small cell lung cancer progression via modulating miR-195-5p/HMGB3 pathway[J]. Cell Cycle, 2021, 20(19): 2040-2052.
10	Kay FU, Kandathil A, Batra K, et al. Revisions to the Tumor, Node, Metastasis staging of lung cancer (8 edition): Rationale, radiologic findings and clinical implications[J]. World J Radiol, 2017, 9(6): 269-279.
11	Liang ZZ, Guo C, Zou MM, et al. circRNA-miRNA-mRNA regulatory network in human lung cancer: an update[J]. Cancer cell international, 2020, 20(1): 1-16.
12	Cheng D, Wang J, Dong Z, et al. Cancer-related circular RNA: diverse biological functions[J]. Cancer cell international, 2021, 21(1): 1-16.
13	Gao P, Wang Z, Hu Z, et al. Circular RNA circ_0074027 indicates a poor prognosis for NSCLC patients and modulates cell proliferation, apoptosis, and invasion via miR-185-3p mediated BRD4/MADD activation[J]. J Cell Biochem, 2020, 121(3): 2632-2642.
14	Wang R, Liu H, Dong M, et al. Exosomal hsa_circ_0000519 modulates the NSCLC cell growth and metastasis via miR-1258/RHOV axis[J]. Open Med (Wars), 2022, 17(1): 826-840.
15	Meng Q, Li Y, Sun Z, et al. CircRNA hsa_circ_0070659 predicts poor prognosis and promotes non-small cell lung cancer (NSCLC) progression via microRNA-377 (miR-377)/Ras-Associated Binding Protein 3C (RAB3C) pathway[J]. Bioengineered, 2022, 13(6): 14578-14594.
16	Duréndez-Sáez E, Torres-Martinez S, Calabuig-Fariñas S, et al. Exosomal microRNAs in non-small cell lung cancer[J]. Transl Cancer Res, 2021, 10(6): 3128-3138.
17	Vlachakis D, Mitsis T, Nicolaides N, et al. Functions, pathophysiology and current insights of exosomal endocrinology[J]. Molecular Med Reports, 2021, 23(1): 26.
18	陈　婷，蒋晓东. 外泌体在非小细胞肺癌中的研究进展[J]. 现代肿瘤医学，2022, 30(11): 2073-2076.
19	Wani TU, Mohi-Ud-Din R, Mir RH, et al. Exosomes harnessed as nanocarriers for cancer therapy-current status and potential for future clinical applications[J]. Current molecular medicine, 2021, 21(9): 707-723.
20	Yang S, Wang D, Zhong S, et al. Tumor-derived exosomal circPSMA1 facilitates the tumorigenesis, metastasis, and migration in triple-negative breast cancer (TNBC) through miR-637/Akt1/β-catenin (cyclin D1) axis[J]. Cell death & disease, 2021, 12(5): 420-430.
21	Zhang N, Nan A, Chen L, et al. Circular RNA circSATB2 promotes progression of non-small cell lung cancer cells[J]. Molecular cancer, 2020, 19(1): 1-16.
22	Fang K, Chen X, Qiu F, et al. Serum-Derived exosomals-Mediated Circular RNA ARHGAP10 Modulates the Progression of Non-Small Cell Lung Cancer Through the miR-638/FAM83F Axis[J]. Cancer Biother Radiopharm, 2022, 37(2): 96-110.
23	Bu L, Tian Y, Wen H, et al. miR-195-5p exerts tumor-suppressive functions in human lung cancer cells through targeting TrxR2[J]. Acta Biochim Biophys Sin (Shanghai), 2021, 53(2): 189-200.

临床资料	变量	血清外泌体has_circ_0060937水平		P值
临床资料	变量	低表达(n＝32)	高表达(n＝31)	P值
病理亚型	腺癌	27(84.38)	21(67.74)	0.121
	鳞癌	5(15.62)	10(32.26)
TNM分期	Ⅰ	8(25.00)	2(6.45)	0.024
	Ⅱ	4(12.50)	1(3.23)
	Ⅲ	7(21.88)	4(22.58)
	Ⅳ	13(40.62)	24(77.42)
淋巴结转移	无	15(46.88)	5(16.13)	0.009
	有	17(53.12)	26(83.87)
远处转移位置(个)	≤2	18(56.25)	9(29.03)	0.029
	>2	14(43.75)	22(70.97)
肿瘤分化程度	低/中	16(50.00)	12(38.71)	0.367
	高	16(50.00)	19(61.29)
LYM(×10⁹/L)	<3.2	30(93.75)	29(90.32)	0.641
	≥3.2	2(6.25)	3(9.68)
Hb(g/L)	<150	29(90.63)	26(83.87)	0.421
	≥150	3(9.37)	5(16.13)
CEA(ng/ml)	<5.0	24(75.00)	22(70.97)	0.719
	≥5.0	8(25.00)	9(29.03)
NLR	<3.0	15(46.88)	10(32.26)	0.236
	≥3.0	17(53.12)	21(67.74)
EGFR突变	野生型	15(46.88)	17(54.84)	0.819
	突变型	6(18.75)	5(16.13)
	未检测	11(34.37)	9(29.03)

临床资料	变量	血清外泌体has_circ_0060937水平		P值
临床资料	变量	低表达(n＝32)	高表达(n＝31)	P值
病理亚型	腺癌	27(84.38)	21(67.74)	0.121
	鳞癌	5(15.62)	10(32.26)
TNM分期	Ⅰ	8(25.00)	2(6.45)	0.024
	Ⅱ	4(12.50)	1(3.23)
	Ⅲ	7(21.88)	4(22.58)
	Ⅳ	13(40.62)	24(77.42)
淋巴结转移	无	15(46.88)	5(16.13)	0.009
	有	17(53.12)	26(83.87)
远处转移位置(个)	≤2	18(56.25)	9(29.03)	0.029
	>2	14(43.75)	22(70.97)
肿瘤分化程度	低/中	16(50.00)	12(38.71)	0.367
	高	16(50.00)	19(61.29)
LYM(×10⁹/L)	<3.2	30(93.75)	29(90.32)	0.641
	≥3.2	2(6.25)	3(9.68)
Hb(g/L)	<150	29(90.63)	26(83.87)	0.421
	≥150	3(9.37)	5(16.13)
CEA(ng/ml)	<5.0	24(75.00)	22(70.97)	0.719
	≥5.0	8(25.00)	9(29.03)
NLR	<3.0	15(46.88)	10(32.26)	0.236
	≥3.0	17(53.12)	21(67.74)
EGFR突变	野生型	15(46.88)	17(54.84)	0.819
	突变型	6(18.75)	5(16.13)
	未检测	11(34.37)	9(29.03)

指　标	单因素分析			多因素分析
指　标	HR	95%CI	P值	HR	95%CI	P值
鳞癌(vs.腺癌)	1.019	0.681~1.526	0.926
TNM分期Ⅲ-Ⅳ期(vs. Ⅰ-Ⅱ期)	1.139	0.964~1.345	0.127
淋巴结转移(vs.无)	0.984	0.844~1.147	0.837
远处转移>2个位置(vs.≤2个)	1.433	1.001~2.130	0.046	1.355	0.904~2.031	0.141
肿瘤低/中分化(vs.高分化)	1.416	0.918~2.186	0.116
LEU≥10×10⁹/L(vs.<10×10⁹/L)	0.990	0.911~1.076	0.819
NEU≥7×10⁹/L(vs.<7×10⁹/L)	1.006	0.925~1.093	0.894
LYM≥3.2×10⁹/L(vs.<3.2×10⁹/L)	0.723	0.535~0.978	0.035	0.863	0.647~1.150	0.314
Hb≥150 g/L(vs.<150 g/L)	0.989	0.978~1.000	0.050	0.991	0.980~1.002	0.120
CEA≥5.0 ng/ml(vs.<5.0 ng/ml)	1.000	1.000~1.001	0.606
NLR≥3.0(vs.<3.0)	1.057	0.986~1.133	0.117
EGFR突变状态(vs.野生型)	1.266	0.952~1.683	0.104
化疗周期≥4个(vs.<4个)	1.246	0.986~1.575	0.066	1.245	0.979~1.584	0.074
血清外泌体has_circ_0060937	1.396	1.197~1.628	0.000	1.375	1.165~1.623	0.000

指　标	单因素分析			多因素分析
指　标	HR	95%CI	P值	HR	95%CI	P值
鳞癌(vs.腺癌)	1.019	0.681~1.526	0.926
TNM分期Ⅲ-Ⅳ期(vs. Ⅰ-Ⅱ期)	1.139	0.964~1.345	0.127
淋巴结转移(vs.无)	0.984	0.844~1.147	0.837
远处转移>2个位置(vs.≤2个)	1.433	1.001~2.130	0.046	1.355	0.904~2.031	0.141
肿瘤低/中分化(vs.高分化)	1.416	0.918~2.186	0.116
LEU≥10×10⁹/L(vs.<10×10⁹/L)	0.990	0.911~1.076	0.819
NEU≥7×10⁹/L(vs.<7×10⁹/L)	1.006	0.925~1.093	0.894
LYM≥3.2×10⁹/L(vs.<3.2×10⁹/L)	0.723	0.535~0.978	0.035	0.863	0.647~1.150	0.314
Hb≥150 g/L(vs.<150 g/L)	0.989	0.978~1.000	0.050	0.991	0.980~1.002	0.120
CEA≥5.0 ng/ml(vs.<5.0 ng/ml)	1.000	1.000~1.001	0.606
NLR≥3.0(vs.<3.0)	1.057	0.986~1.133	0.117
EGFR突变状态(vs.野生型)	1.266	0.952~1.683	0.104
化疗周期≥4个(vs.<4个)	1.246	0.986~1.575	0.066	1.245	0.979~1.584	0.074
血清外泌体has_circ_0060937	1.396	1.197~1.628	0.000	1.375	1.165~1.623	0.000

[1]	Xiaoyan Wang, You Xiao, Ge Xiao, Zhenquan Wang. CT characteristics and risk factors of lung metastasis in elderly patients with colorectal cancer [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2023, 17(05): 506-509.
[2]	Yating You, Zhoukui Bi, Liang Guo, Li Bai. Clinicopathological features and therapeutic efficacy of non-small cell lung cancer with uncommon EGFR mutation [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2023, 16(05): 635-639.
[3]	Tianxiu Wu, Yu Xu, Xiuqing Liao, Wei Yao, Guansong Wang, Yu Yang, Bin Wang, Liang Guo, Mingzhou Zhang, Guoming Wu, Li Luo, Li Bai, Yan Wang, Mingdong Hu, Zhi Xu. Relationship between BRCA1/2 gene mutation and efficacy of platinum-base chemotherapy in driver mutation-negative stage Ⅲ/Ⅳ non-small cell lung cancer [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2023, 16(05): 615-623.
[4]	Yiran Li, Yuxiu Wang, Yan Zhu, Meng Wang, Ying Liu, Wenjin Yan, Xingxiang Xu, Lingfeng Min. Analysis of differential genes that affect the efficacy of Nivolumab and Pembrolizumab in the treatment of non-small cell lung cancer based on GEO database [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2023, 16(01): 20-25.
[5]	Yuan Wang, Yi Yang, Yunfei Mou, Fuqiang Ren, Xin Huang. Analysis of postoperative osimertinib targeted therapy in patients with resectable non-small cell lung cancer [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2022, 15(05): 657-660.
[6]	Ling Ma, Yinglong Li, Na Yue, Lifei Yang. Expression and clinical value of differential proteins in exosomes from non-small cell lung cancer [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2022, 15(03): 327-330.
[7]	Yating Wu, Shenghang Zhang, Shuiliang Wang. Research progress in the role of dysregulated RNA m⁶A modification in breast cancer metastasis [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2023, 13(01): 45-52.
[8]	Zhuolin Li, Ruxue Jia, Yating Wu, Shenghang Zhang, Shuiliang Wang. Advances in molecular mechanisms underlying tumor metastasis and its targeted intervention [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2022, 12(01): 51-58.
[9]	Li Ma. Value analysis of CT perfusion combined with angiography in predicting prognosis of neurological function in patients with acute cerebral infarction [J]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2023, 13(04): 229-234.
[10]	Jiu Yang, Mei Hong, Zhiyuan Liu, Nuo Zhu. Yiqi Chutan recipe combined with chemotherapy for treatment of patients with advanced non-small cell lung cancer: short-term curative effect and impact on serum levels of IL-2 and TNF-α and immune function [J]. Chinese Journal of Clinicians(Electronic Edition), 2021, 15(12): 948-953.
[11]	Bo Zhang, Bo Jin. Progress in research of Met as a target in non-small cell lung cancer [J]. Chinese Journal of Clinicians(Electronic Edition), 2021, 15(10): 797-800.
[12]	Kexin Tang, Xi Lin, Hong Shan. Doxorubicin-loaded fluorescent carbon dots with PEI passivation inhibited proliferation, migration and invasion of non-small cell lung cancer cells [J]. Chinese Journal of Interventional Radiology(Electronic Edition), 2022, 10(02): 131-136.
[13]	Leilei Shen, Yang Liu. The staging evolution and treatment strategies of stage ⅠB non-small cell lung cancer [J]. Chinese Journal of Thoracic Surgery(Electronic Edition), 2022, 09(04): 246-254.
[14]	Xiao Liang, Lei Wang, Tao Jiang. Progress in surgical treatment of non-small cell lung cancer invading the chest wall [J]. Chinese Journal of Thoracic Surgery(Electronic Edition), 2022, 09(03): 157-163.
[15]	Jianqiao Cai, Jing Huang, Lei Jiang. Double sleeve uniportal video-assisted thoracoscopic lobectomy—a retrospective study from shanghai pulmonary hospital [J]. Chinese Journal of Thoracic Surgery(Electronic Edition), 2022, 09(03): 144-149.

Please choose a citation manager

Content to export