SPARC表达水平与非小细胞肺癌患者预后关系的meta分析

doi:10.3969/j.issn.1004-583X.2023.11.002

摘要/Abstract

摘要：

目的富含半胱氨酸的酸性分泌蛋白(secreted protein acidic and rich in cysteine,SPARC),也称为骨粘连蛋白(osteonectin)及基底膜-40(BM-40),是一种与细胞分泌有关的小分子糖蛋白。在多种恶性肿瘤中发现SPARC发挥着促进肿瘤侵袭与转移的作用,且与肿瘤患者预后不佳有关。目前SPARC在非小细胞肺癌(non-small-cell lung cancer, NSCLC)中的预后作用仍有争议,故本研究采用meta分析的方法评估SPARC在NSCLC患者中的表达水平及与预后的关系。方法本研究通过对PubMed、Web of Science、EMBASE、Cochrane Library、中国知网(CNKI)、万方数据库进行全面检索,收集纳入研究SPARC表达水平与NSCLC患者预后关系的文献及相关数据,采用Review Manager 5.4软件进行数据分析,计算危险比(hazard ratio, $H R$ )及 95% 置信区间( $C I$ )以评估SPARC表达与NSCLC患者总生存期(overall survival,OS)的关系。结果总共纳入5项研究,共计430例患者,对这些研究进行异质性检验( $I 2$ =31%, $P$ =0.21),采用固定效应模型进行数据合并的 $H R$ 值为1.77,95%可信区间为1.41~2.21,表明SPARC高水平表达与NSCLC患者较差的OS相关。针对SPARC是否有甲基化进行了亚组分析,结果显示在无甲基化的各研究中无异质性( $I 2$ =0%, $P$ =0.89),合并的 $H R$ 值为1.97,95% $C I$ 为1.40-2.79,有甲基化的各研究中有明显的异质性( $I 2$ =80%, $P$ =0.03),合并的 $H R$ 值为1.63,95% $C I$ 为1.21-2.19,表明SPARC的预后意义因是否有甲基化而改变。结论 SPARC高表达是非小细胞肺癌患者预后不良的一个指标,可作为评估非小细胞肺癌患者预后的潜在生物标记物。

关键词: 癌, 非小细胞肺, SPARC, 总生存期, 预后, meta分析

Abstract:

Objective Secreted protein acidic and rich in cysteine (SPARC), also known as osteonectin and basal membrane-40 (BM-40), is a small molecule glycoprotein related to cell secretion. It promotes the invasion and metastasis of a variety of malignant tumors, which is correlated with the poor prognosis of tumor patients. At present, the prognostic role of SPARC in non-small cell lung cancer (NSCLC) is still controversial. This meta-analysis aims to assess the expression level of SPARC in NSCLC patients and its correlation with the prognosis. Methods Articles reporting the expression level of SPARC in NSCLC patients with and its correlation with the prognosis were systematically searched in the PubMed, Web of Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI) and Wanfang databases. Data analysis was performed using Review Manager 5.4 software. Hazard ratio ( $H R$ ) and 95% Confidence interval ( $C I$ ) were calculated to assess the expression level of SPARC and its correlation with the overall survival (OS) of NSCLC patients. Results A total of 5 studies involving 430 NSCLC patients were recruited. Heterogeneity was tested ( $I 2$ =31%, $P$ =0.21), and the $H R$ of the pooled data using a fixed effects model was 1.77(95% $C I$ : 1.41-2.21), indicating that the high level of SPARC was correlated with a poor OS in NSCLC patients. A subgroup analysis based on the methylation of SPARC was conducted. There was no heterogeneity ( $I 2$ =0%, $P$ =0.89) in the articles without reporting the methylation of SPARC, with the combined $H R$ of 1.97(95% $C I$ : 1.40-2.79). A significant heterogeneity was detected in the articles reporting the methylation of SPARC ( $I 2$ =80%, $P$ =0.03), with the combined $H R$ of 1.63(95% $C I$ : 1.21-2.19), indicating that the prognostic significance of SPARC was changed by the presence or absence of methylation. Conclusion High level of SPARC predicts a poor prognosis in NSCLC patients, which can be used as a potential biomarker to assess the prognosis of NSCLC.

Key words: carcinoma, non-small-cell lung, SPARC, overall survival, prognosis, meta-analysis

中图分类号:

R730.26

张娜, 孙越, 董晗, 赵鹏, 杨昕, 祁源, 王玲玲. SPARC表达水平与非小细胞肺癌患者预后关系的meta分析[J]. 临床荟萃, 2023, 38(11): 972-978.

Zhang Na, Sun Yue, Dong Han, Zhao Peng, Yang Xin, Qi Yuan, Wang Lingling. Correlation between the expression level of SPARC and prognosis in patients with non-small cell lung cancer: A meta-analysis[J]. Clinical Focus, 2023, 38(11): 972-978.

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链接本文: https://lchc.magtechjournal.com/CN/10.3969/j.issn.1004-583X.2023.11.002

https://lchc.magtechjournal.com/CN/Y2023/V38/I11/972

图/表 6

图1 文献筛选流程图

Fig.1 Flow chart of literature screening

表1 纳入文献的基本特征

Tab.1 Basic characteristics of enrolled studies

第一作者	出版年份	国家	病例数	检测方法	随访时间	组织学类型	分级	生存时间		无病生存期
第一作者	出版年份	国家	病例数	检测方法	随访时间	组织学类型	分级	$H R$	95% $C I$	$H R$	95% $C I$
Fabrizio^[12]	2020	Italy	59	IHC	52	NSCLC	Ⅰ-Ⅲ	1.46	1.07-2.00	0.98	0.61-1.57
Kurtul^[13]	2014	Turkey	84	IHC	12.5	NSCLC	Ⅲ	1.97	1.20-3.21	1.67	1.05-2.66
Suzuki^[14]	2005	Japan	84	IHC	NA	NSCLC	Ⅰ-Ⅳ	4.65	1.75-12.35	NA	NA
Xu^[15]	2019	China	90	IHC	NA	SCC	Ⅰ-Ⅳ	2.26	1.11-4.59	NA	NA
Koukourakis^[16]	2003	Britain	113	IHC	55.9	NSCLC	Ⅰ-Ⅱ	1.77	0.91-3.44	NA	NA

表1 纳入文献的基本特征

Tab.1 Basic characteristics of enrolled studies

第一作者	出版年份	国家	病例数	检测方法	随访时间	组织学类型	分级	生存时间		无病生存期
第一作者	出版年份	国家	病例数	检测方法	随访时间	组织学类型	分级	$H R$	95% $C I$	$H R$	95% $C I$
Fabrizio^[12]	2020	Italy	59	IHC	52	NSCLC	Ⅰ-Ⅲ	1.46	1.07-2.00	0.98	0.61-1.57
Kurtul^[13]	2014	Turkey	84	IHC	12.5	NSCLC	Ⅲ	1.97	1.20-3.21	1.67	1.05-2.66
Suzuki^[14]	2005	Japan	84	IHC	NA	NSCLC	Ⅰ-Ⅳ	4.65	1.75-12.35	NA	NA
Xu^[15]	2019	China	90	IHC	NA	SCC	Ⅰ-Ⅳ	2.26	1.11-4.59	NA	NA
Koukourakis^[16]	2003	Britain	113	IHC	55.9	NSCLC	Ⅰ-Ⅱ	1.77	0.91-3.44	NA	NA

图2 SPARC表达水平与非小细胞肺癌患者OS关系的森林图

Fig. 2 Forest plot for the association between SPARC expression level and OS in NSCLC patients

图3 亚组分析

Fig.3 Subgroup analysis

图4 OS发表偏倚的漏斗图

Fig. 4 Funnel plot of publication bias for OS

图5 SPARC表达与OS关系的敏感性分析

Fig. 5 Sensitivity analysis of the relationship between SPARC expression and OS

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