KLHL7在非小细胞肺癌中的表达及其临床意义

黄庭; 贡会源; 唐震; 李伟; 张雷; 李小军; 高雄

doi:10.16766/j.cnki.issn.1674-4152.003061

KLHL7在非小细胞肺癌中的表达及其临床意义

doi: 10.16766/j.cnki.issn.1674-4152.003061

蚌埠医学院第一附属医院胸外科, 安徽蚌埠 233004

基金项目:

安徽省高等学校自然科学研究项目 KJ2020A0575

安徽省中央引导地方科技发展项目 2020b07030008

详细信息

通讯作者:
唐震，E-mail: 15855776000@139.com

中图分类号: R734.2 R730.43
计量
- 文章访问数: 146
- HTML全文浏览量: 36
- PDF下载量: 13
- 被引次数: 0
出版历程
- 收稿日期: 2022-08-28
- 网络出版日期: 2023-08-28

Expression of KLHL7 in non-small cell lung cancer and its clinical significance

Department of Thoracic Surgery, the First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, China

摘要

摘要: 目的探讨非小细胞肺癌(NSCLC)组织及癌旁组织中Kelch样家族成员7(KLHL7)的表达情况与NSCLC患者预后的相关性。方法运用TIMER、UALCAN数据库分析KLHL7在NSCLC组织和癌旁组织中的表达差异；并通过Kaplan-Meier plotter网站分析KLHL7表达水平对NSCLC患者预后的影响。选取2014年1月—2016年12月于蚌埠医学院第一附属医院接受手术治疗的96例NSCLC患者，采用免疫组化的方法检测NSCLC组织及癌旁组织中KLHL7的表达水平。结果通过生物信息学分析发现KLHL7在NSCLC组织中表达明显升高并提示预后不良。免疫组化结果显示KLHL7蛋白在NSCLC组织中的表达阳性率明显高于癌旁组织(57.3% vs.3.1%, P < 0.001)。KLHL7高表达与肿瘤直径>3 cm、肿瘤细胞低分化、淋巴结转移、高TNM分期显著相关(均P < 0.05)。K-M生存分析结果表明，肿瘤直径、肿瘤细胞分化程度、淋巴结转移、TNM分期和KLHL7表达水平均为影响NSCLC患者的预后因素(均P < 0.05)。多因素分析结果显示，肿瘤细胞低分化、淋巴结转移、高TNM分期和KLHL7高表达为影响NSCLC患者术后生存时间的独立危险因素(均P < 0.05)。结论 KLHL7在NSCLC组织中高表达且与肿瘤进展相关，是影响NSCLC患者预后的独立危险因素，对预后评估具有一定的临床价值。
- Kelch样家族成员7 /
- 非小细胞肺癌 /
- 生物信息学 /
- 免疫组化 /
- 临床病理学特征 /
- 预后
Abstract: Objective To investigate the correlation between the expression of Kelch-like family member 7 (KLHL7) in non-small cell lung cancer (NSCLC) tissue and paracancerous tissue and the prognosis of NSCLC patients. Methods The difference of KLHL7 expression in NSCLC tissue and paracancerous tissue was analyzed by using TIMER and UALCAN database respectively. The Kaplan-Meier plotter website was used to analyze the effects of KLHL7 expression levels on the prognosis of patients with NSCLC. A total of 96 patients with NSCLC who received surgical treatment in the First Affiliated Hospital of Bengbu Medical College from January 2014 to December 2016 were selected. Immunohistochemistry was used to detect the expression levels of KLHL7 in NSCLC tissue and paracancerous tissue. Results Bioinformatics analysis found that the expression of KLHL7 in NSCLC tissue was significantly increased and the prognosis was poor. Immunohistochemistry staining showed that the positive rate of KLHL7 protein expression in NSCLC tissue was significantly higher than that in paracancerous tissue (57.3% vs. 3.1%, P < 0.001). High KLHL7 expression was significantly correlated with diameter of tumor >3 cm, low tumor cell differentiation, lymph node metastasis and high TNM stage (all P < 0.05). The results of K-M survival analysis showed that tumor diameter, tumor cell differentiation, lymph node metastasis, TNM stage and KLHL7 expression level were all prognostic factors of NSCLC patients (all P < 0.05). Multivariate analysis showed that low tumor cell differentiation, lymph node metastasis, high TNM stage and high KLHL7 expression were independent risk factors affecting postoperative survival time of NSCLC patients (all P < 0.05). Conclusion KLHL7 is highly expressed in NSCLC tissue and correlated with tumor progression, which is an independent risk factor affecting prognosis of patients with NSCLC and has certain clinical value for prognosis assessment.
- Kelch-like family member 7 /
- Non-small cell lung cancer /
- Bioinformatics /
- Immunohistochemistry /
- Clinicopathological features /
- Prognosis

HTML全文

图 1 KLHL7在各肿瘤及癌旁组织中的表达情况

注：^aP < 0.05, ^bP < 0.01。

Figure 1. Expression of KLHL7 in tumors and paracancerous tissues

下载: 全尺寸图片幻灯片

图 2 KLHL7基因表达与NSCLC患者生存率的关系

Figure 2. Relationship between KLHL7 gene expression and survival rate of NSCLC patients

下载: 全尺寸图片幻灯片

图 3 免疫组化检测KLHL7蛋白在NSCLC和癌旁组织的表达情况(EliVision法)

注：A为KLHL7在鳞癌组织中低水平表达(×400)；B为KLHL7在鳞癌组织中高水平表达(×400)；C为KLHL7在腺癌组织中低水平表达(×200)；D为KLHL7在腺癌组织中高水平表达(×400)。

Figure 3. Immunohistochemical detection of KLHL7 protein expression in NSCLC and paracancerous tissues (EliVision method)

下载: 全尺寸图片幻灯片

图 4 KLHL7的表达水平对肺癌术后生存时间的影响

Figure 4. Effect of KLHL7 expression level on survival time after lung cancer surgery

下载: 全尺寸图片幻灯片

表 1 KLHL7在肺癌组织和癌旁组织中的表达情况[例(%)]

Table 1. Expression of KLHL7 in lung cancer and paracancer tissues [cases(%)]

组别	例数	KLHL7表达水平		χ²值	P值
组别	例数	高表达	低表达	χ²值	P值
肺癌组织	96	55(57.3)	41(42.7)	66.800	< 0.001
癌旁组织	96	3(3.1)	93(96.9)

下载: 导出CSV

表 2 KLHL7表达与NSCLC患者临床病理特征的相关性分析(例)

Table 2. Correlation analysis of KLHL7 expression and clinicopathologic features of NSCLC patients(cases)

项目	KLHL7表达		χ²值	P值	项目	KLHL7表达		χ²值	P值
项目	高表达(n=55)	低表达(n=41)	χ²值	P值	项目	高表达(n=55)	低表达(n=41)	χ²值	P值
年龄(岁)			0.254	0.614	肿瘤病理分型			1.494	0.222
< 60	27	18			鳞癌	8	10
≥60	28	23			腺癌	47	31
性别			0.550	0.458	肿瘤细胞分化程度			5.324	0.021
男性	28	24			中高分化	39	37
女性	27	17			低分化	16	4
吸烟			0.603	0.437	淋巴结转移			8.869	0.003
是	16	15			是	20	4
否	39	26			否	35	37
肿瘤直径(cm)			13.694	< 0.001	TNM分期			7.923	0.005
≤3	13	25			Ⅰ+Ⅱ	36	37
>3	42	16			Ⅲ	19	4
肿瘤大体类型			0.397	0.529
中央型	30	25
周围型	25	16

下载: 导出CSV

表 3 NSCLC患者预后的单因素及多因素COX回归分析

Table 3. Univariate and multivariate COX regression analysis of the prognosis of NSCLC patients

变量	单因素COX回归分析			多因素COX回归分析
变量	HR	95%CI	P值	B	SE	Waldχ²	HR	95%CI	P值
年龄	0.857	0.514~1.428	0.553
性别	0.921	0.554~1.529	0.750
吸烟	0.850	0.484~1.492	0.571
肿瘤直径	3.078	1.686~5.619	< 0.001	0.360	0.344	1.097	1.434	0.731~2.813	0.295
肿瘤大体类型	1.403	0.841~2.340	0.195
肿瘤病理分型	0.905	0.480~1.705	0.758
分化程度	0.335	0.192~0.583	< 0.001	-1.141	0.317	12.940	0.320	0.172~0.595	< 0.001
淋巴结转移	3.055	1.792~5.206	< 0.001	0.798	0.326	5.983	2.222	1.172~4.212	0.014
TNM分期	4.377	2.549~7.514	< 0.001	1.049	0.321	10.699	2.856	1.523~5.356	0.001
KLHL7表达水平	4.900	2.625~9.146	< 0.001	1.042	0.354	8.637	2.834	1.415~5.677	0.003
注：赋值方法如下，年龄 < 60岁=0，≥60岁=1；女性=0，男性=1；不吸烟=0，吸烟=1；肿瘤直径≤3 cm=0，>3 cm=1；中央型=0，周围型=1；鳞癌=0，腺癌=1；低分化=0，中高分化=1；无淋巴结转移=0，有淋巴结转移=1；Ⅰ+Ⅱ期=0，Ⅲ期=1；KLHL7低表达=0，高表达=1。

下载: 导出CSV

参考文献(20)

[1]	SIEGEL R L, MILLER K D, FUCHS H E, et al. Cancer statistics, 2022[J]. CA Cancer J Clin, 2022, 72(1): 7-33. doi: 10.3322/caac.21708
[2]	LI M, MENG G X, LIU X W, et al. Deep-LC: a novel deep learning method of identifying non-small cell lung cancer-related genes[J]. Front Oncol, 2022, 12: 949546. DOI: 10.3389/fonc.2022.949546.
[3]	GUO H Y, ZHANG J, QIN C, et al. Biomarker-targeted therapies in non-small cell lung cancer: current status and perspectives[J]. Cells, 2022, 11(20): 3200-3224. doi: 10.3390/cells11203200
[4]	刘彩霞, 贾金虎, 井丽君, 等. 新靶位基因RET在非小细胞肺癌中的研究进展[J]. 中国医药, 2019, 14(4): 618-620. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGYG201904035.htm LIU C X, JIA J H, JING L J, et al. Research progress of new target gene RET in non-small cell lung cancer[J]. China Medicine, 2019, 14(4): 618-620. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGYG201904035.htm
[5]	SUN T S, LIU Z N, YANG Q. The role of ubiquitination and deubiquitination in cancer metabolism[J]. Mol Cancer, 2020, 19(1): 146. doi: 10.1186/s12943-020-01262-x
[6]	DENG L, MENG T, CHEN L, et al. The role of ubiquitination in tumorigenesis and targeted drug discovery[J]. Signal Transduct Target Ther, 2020, 5(1): 11-39. doi: 10.1038/s41392-020-0107-0
[7]	GUO J H, ZHAO J, FU W, et al. Immune evasion and drug resistance mediated by USP22 in cancer: novel targets and mechanisms[J]. Front Immunol, 2022, 13: 918314. DOI: 10.3389/fimmu.2022.918314.
[8]	ANGIUS A, UVA P, BUERS I, et al. Bi-allelic mutations in KLHL7 cause a crisponi/CISS1-like phenotype associated with early-onset retinitis pigmentosa[J]. Am J Hum Genet, 2018, 102(4): 713-722.
[9]	WANG P, SONG J B, YE D. CRL3s: the BTB-CUL3-RING E3 ubiquitin ligases[J]. Adv Exp Med Biol, 2020, 1217: 211-223.
[10]	KUROZUMI S, JOSEPH C, SONBUL S, et al. Clinical and biological roles of Kelch-like family member 7 in breast cancer: a marker of poor prognosis[J]. Breast Cancer Res Treat, 2018, 170(3): 525-533. doi: 10.1007/s10549-018-4777-z
[11]	XIA C F, DONG X S, LI H, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants[J]. Chin Med J (Engl), 2022, 135(5): 584-590. doi: 10.1097/CM9.0000000000002108
[12]	WEI C H, DONG X M, LU H, et al. LPCAT1 promotes brain metastasis of lung adenocarcinoma by up-regulating PI3K/AKT/MYC pathway[J]. J Exp Clin Cancer Res, 2019, 38(1): 95-111. doi: 10.1186/s13046-019-1092-4
[13]	郭莹, 高天慧, 赵孟阳, 等. 晚期非小细胞肺癌淋巴细胞亚群及细胞因子与免疫疗效的关系研究[J]. 中华全科医学, 2022, 20(9): 1462-1465. doi: 10.16766/j.cnki.issn.1674-4152.002623 GUO Y, GAO T H, ZHAO M Y, et al. Study on the relationship between lymphocyte subsets, cytokines and immune efficacy in advanced non-small cell lung cancer[J]. Chinese Journal of General Practice, 2022, 20(9): 1462-1465. doi: 10.16766/j.cnki.issn.1674-4152.002623
[14]	RIUDAVETS M, SULLIVAN I, ABDAYEM P, et al. Targeting HER2 in non-small-cell lung cancer (NSCLC): a glimpse of hope? An updated review on therapeutic strategies in NSCLC harbouring HER2 alterations[J]. ESMO Open, 2021, 6(5): 100260. DOI: 10.1016/j.esmoop.2021.100260.
[15]	WANG M N, HERBST R S, BOSHOFF C. Toward personalized treatment approaches for non-small-cell lung cancer[J]. Nat Med, 2021, 27(8): 1345-1356. doi: 10.1038/s41591-021-01450-2
[16]	CHOI J, LEE K, INGVARSDOTTIR K, et al. Loss of KLHL6 promotes diffuse large B-cell lymphoma growth and survival by stabilizing the mRNA decay factor roquin2[J]. Nat Cell Biol, 2018, 20(5): 586-596. doi: 10.1038/s41556-018-0084-5
[17]	YE G H, WANG J, YANG W L, et al. The roles of KLHL family members in human cancers[J]. Am J Cancer Res, 2022, 12(11): 5105-5139.
[18]	MORAIS-RODRIGUES F, SILV E R, KATO R B, et al. Analysis of the microarray gene expression for breast cancer progression after the application modified logistic regression[J]. Gene, 2020, 726: 144168. DOI: 10.1016/j.gene.2019.144168.
[19]	HAN M, YANG H J, LIN Q. KLHL14, an ovarian and endometrial-specific gene, is over-expressed in ovarian and endometrial cancer[J]. Math Biosci Eng, 2019, 17(2): 1702-1717.
[20]	KUROZUMI S, JOSEPH C, SONBUL S, et al. Clinical and biological roles of Kelch-like family member 7 in breast cancer: a marker of poor prognosis[J]. Breast Cancer Res Treat, 2018, 170(3): 525-533. doi: 10.1007/s10549-018-4777-z