术前红细胞分布宽度与胃癌患者预后关系的Meta分析
Meta-Analysis of the Relationship between Preoperative Erythrocyte Distribution Width and Prognosis in Patients with Gastric Cancer
DOI: 10.12677/ACM.2023.13122866, PDF, HTML, XML, 下载: 183  浏览: 321 
作者: 雷 源*, 魏亚利:延安大学附属医院消化内科,陕西 延安
关键词: 红细胞分布宽度胃癌预后Meta分析Erythrocyte Distribution Width Gastric Cancer Prognosis Meta-Analysis
摘要: 目的:探讨胃癌患者术前红细胞分布宽度(Red Blood Cell Distribution Width, RDW)与其预后的关系。方法:计算机检索中国知网、万方、维普、中国生物医学、PubMed、EMbase、Cochrane Library、Web of Science等数据库,收集自建库至2023年2月19日公开发表的有关胃癌患者术前RDW水平与其预后关系的文献。根据纳排标准筛选文献,对纳入的文献进行质量评价。主要研究指标包括总生存期(Overall Survival, OS)、无病生存期(Disease-Free Survival, DFS)和癌症特异生存时间(Cancer-Specific Survival, CSS)。采用Rev Man 5.4软件进行Meta分析,合并值为风险比(Hazard Ratio, HR)及95%置信区间(Confidence, CI)。结果:本次共纳入10项回顾性研究,总计1786例胃癌患者,来自中国及日本。纳入研究的纽卡斯尔–渥太华量表(Newcastle-Ottawa Scale, NOS)评分均为6分及以上。Meta分析结果显示,术前高RDW与胃癌患者OS较低显著相关(HR = 2.14, 95% CI 1.71~2.68, P < 0.00001),与胃癌患者DFS较差显著相关(HR = 1.76, 95% CI 1.35~2.31, P < 0.0001),与胃癌患者CSS (HR = 2.81, 95% CI 2.21~3.57, P < 0.00001)较差显著相关。结论:胃癌患者术前高RDW水平可能是中国或日本胃癌患者预后的独立危险因素;但仍然需要更大样本量、前瞻性研究进一步验证。
Abstract: Objective: To explore the relationship between preoperative red blood cell distribution width (RDW) and prognosis in patients with gastric cancer. Methods: The databases of CNKI, VIP, Wanfang, China Biomedicine, Pub Med, Cochrane Library, EMbase and Web of Science were searched by com-puter. Literatures on the relationship between preoperative RDW level and prognosis of patients with gastric cancer were collected from the establishment of the database to the publication on February 19, 2023. The literature was screened according to the exclusion criteria, and the quality of the included literature was evaluated. The main study indexes were overall survival (OS), dis-ease-free survival (DFS) and cancer-specific survival (CSS). Meta-analysis was performed using Rev Man 5.4 software and the combined values were hazard ratio (HR) and 95% confidence interval (CI). Results: A total of 1786 patients with gastric cancer were included in 10 retrospective studies, all from China or Japan. The Newcastle-Ottawa scale (NOS) scores included in the study were all 6 points or above. Meta-analysis showed that high preoperative RDW was significantly correlated with lower OS in gastric cancer patients (HR = 2.14, 95% CI 1.71~2.68, P < 0.00001), and poor DFS in gastric cancer patients (HR = 1.76, 95% CI 1.35~2.31, P < 0.0001). It was significantly associated with poor CSS (HR = 2.81, 95% CI 2.21~3.57, P < 0.00001) in gastric cancer patients. Conclusion: High preoperative RDW level may be an independent prognostic risk factor for gastric cancer pa-tients in China and Japan. However, a larger sample size and prospective studies are still needed for further verification.
文章引用:雷源, 魏亚利. 术前红细胞分布宽度与胃癌患者预后关系的Meta分析[J]. 临床医学进展, 2023, 13(12): 20356-20362. https://doi.org/10.12677/ACM.2023.13122866

1. 引言

胃癌作为全球第五大常见癌症,在癌症相关死因中排名第三 ‎[1] ,病死率高达70% ‎[2] 。由于胃癌早期临床症状不典型,且目前缺乏特异、可靠的胃癌肿瘤标志物,大多数胃癌患者确诊时已处于中晚期阶段,因此,五年生存率仅约20% ‎[3] 。目前,内镜联合病理学活检成为确诊胃癌的主要手段,然而价格昂贵且技术要求高。因此,探索一种廉价有效、非侵入性的检测方法对于大多数患者来说是非常必要和迫切的。

红细胞分布宽度(RDW)作为一种反映外周血中红细胞体积异质性的指标,既往主要用于各种类型贫血的诊断及鉴别诊断。近年来,广泛的研究结果表明,RDW作为常规的血液检测结果之一,与胃癌的病理特征及预后密切相关,结果不全一致。

因此,本文旨在进一步探讨术前RDW在胃癌患者预后中的作用,从而方便临床早期识别胃癌并改善胃癌疾病预后。

2. 资料与方法

2.1. 纳入标准

① 研究文献类型:国内外公开发表的有关胃癌患者术前RDW水平与其预后关系的研究;② 研究对象:经病理活检确诊的胃癌患者;③ 暴露因素:根据胃癌患者术前RDW水平分为高RDW组和低RDW组;④ 结局指标:总生存期(Overall Survival, OS)、无病生存期(Disease-Free Survival, DFS)和癌症特异生存时间(Cancer-Specific Survival, CSS)。

2.2. 排除标准

① 非原发性胃癌;② 综述、动物研究、系统评价、病例报道等类型文献;③ 无法获取全文的文献。

2.3. 检索策略

在中国知网、维普、万方、中国生物医学、PubMed、Cochrane Library、EMbase、Web of Science等数据库中检索有关术前RDW与胃癌预后关系的文献,时间为从建库至2023年2月19日。英文检索采用主题词 + 自由词的检索方式,且根据PubMed的Mesh确定检索名。中文检索词为红细胞分布宽度、胃肿瘤、胃癌。英文检索式见框1。

框1 PubMed检索策略

(“Stomach Neoplasms” [Mesh]) OR (Neoplasm, Stomach [Title/Abstract]) OR (Stomach Neoplasm [Title/Abstract]) OR (Neoplasms, Stomach [Title/Abstract]) OR (Gastric Neoplasms [Title/Abstract]) OR (Gastric Neoplasm [Title/Abstract]) OR (Neoplasm, Gastric [Title/Abstract]) OR (Neoplasms, Gastric [Title/Abstract]) OR (Cancer of Stomach [Title/Abstract]) OR (Stomach Cancers [Title/Abstract]) OR (Gastric Cancer [Title/Abstract]) OR (Cancer, Gastric [Title/Abstract]) OR (Cancers, Gastric [Title/Abstract]) OR (Gastric Cancers [Title/Abstract]) OR (Stomach Cancer [Title/Abstract]) OR (Cancer, Stomach [Title/Abstract]) OR (Cancers, Stomach [Title/Abstract]) OR (Cancer of the Stomach [Title/Abstract]) OR (Gastric Cancer, Familial Diffuse [Title/Abstract]) AND (“Erythrocyte Indices” [Mesh]) OR (red cell distribution width [Title/Abstract]) OR (RDW [Title/Abstract]) OR (erythrocyte distribution width [Title/Abstract])

2.4. 数据提取和质量评估

由二位研究者根据纳排标准独立筛选文献、提取数据,并进行质量评价。质量评价采用纽卡斯尔–渥太华评价量表(Newcastle-Ottawa Quality Assessment Scale, NOS),0~3分为低质量,4~6分为中等质量,7~9分为高质量。收集资料包括第一作者姓名、出版年份、地区、样本量、性别、肿瘤分期、中位随访时间、RDW临界值、结局指标及其HR值、95% CI。

2.5. 统计学分析

采用RevMan 5.4软件进行统计学分析。效应量以HR值及95% CI表示;用Q检验评估异质性,用I2和P值评估异质性大小,若I2 < 50%、P > 0.10,则选择固定效应模型;若I2 > 50%、P < 0.10,则选择随机效应模型,且对异质性大者进行敏感性分析。

3. 结果

3.1. 文献检索结果

本研究共检索到253篇文献,严格按照纳排标准,并删除重复文献,其中2篇文献 ‎[7] ‎[8] ‎[9] 分别针对年龄、胃癌分期(早期、进展期)进行了分层分析,因此我们将其均视为2项研究,最终共10篇文献纳入meta分析,筛选流程见图1

3.2. 文献基本特征

我们共纳入10项回顾性研究,总计1786例胃癌患者,来自中国或日本,NOS评分均在6分及以上,属于中高质量研究。文献基本特征及质量评价见表1

Figure 1. Literature screening process and results

图1. 文献筛选流程及结果

3.3. Meta分析结果

3.3.1. 术前RDW与OS的关系

Figure 2. Forest map of the relationship between RDW and overall survival of patients with gastric cancer

图2. RDW与胃癌患者总生存期关系的森林图

共9项 ‎[5] - ‎[11] 研究报道了术前RDW与胃癌OS的关系。通过异质性检验,I2 = 23% < 50%,且Q检验的P = 0.24 > 0.1,提示本次研究纳入的文献之间异质性较小,因此采用固定效应模型进行meta分析。Meta分析结果表明术前高RDW与OS较低显著相关(HR = 2.14, 95% CI 1.71~2.68, P < 0.00001)。见图2

3.3.2. 术前RDW与DFS的关系

共4项 ‎[4] ‎[7] ‎[8] 研究报道了术前RDW与胃癌DFS的关系。经过异质性检验,I2 = 0% < 50%,且Q检验的P = 0.46 > 0.1,异质性较低,因此采用固定效应模型进行meta分析。Meta分析结果表明术前高RDW与DFS较差显著相关(HR = 1.76, 95% CI 1.35~2.31, P < 0.0001)。见图3

Figure 3. Forest map of the relationship between RDW and disease-free survival in patients with gastric cancer

图3. RDW与胃癌患者无病生存期关系的森林图

3.3.3. 术前RDW与CSS的关系

共2项 ‎[9] 研究报道了术前RDW与胃癌CSS的关系。通过异质性检验,I2 = 0% < 50%,且Q检验的P = 0.94 > 0.1,异质性较低,所以采用固定效应模型进行meta分析。Meta分析结果表明术前高RDW与CSS较差显著相关(HR = 2.81, 95% CI 2.21~3.57, P < 0.00001)。见图4

Figure 4. Forest map of the relationship between RDW and cancer-specific survival in patients with gastric cancer

图4. RDW与胃癌患者癌症特异性生存期关系的森林图

Table 1. Basic features of the included literature

表1. 纳入文献的基本特征

4. 讨论

本文通过纳入10项研究,共计1786例经病理活检确诊的胃癌患者,通过meta分析研究了术前RDW与胃癌患者预后的关系。结果显示,术前高RDW可能是胃癌患者预后不良的影响因素之一,但本研究仅纳入中国及日本等地区,样本量较少,仍需更大样本量前瞻性研究验证。

以往的研究支持慢性炎症在各种恶性肿瘤发生、进展中的作用 ‎[10] ‎[11] ‎[12] ,肿瘤微环境中炎症细胞分泌的细胞因子可影响肿瘤细胞的增殖及迁移 ‎[13] 。研究表明,血液学参数如PDW ‎[7] 、MCV ‎[14] 、CRP、白细胞、NLR、PLR ‎[15] 等与多种恶性肿瘤的诊断及预后评估相关。TNM分期作为胃癌恶性程度评价的主要标准,是通过手术后的一些病理指标获取,例如肿瘤直径、是否穿透浆膜、有无淋巴结转移及远处转移等。但这些指标大多来自术后病理结果,存在滞后性。

近年来,癌胚抗原(CEA)、癌抗原(CA125)、癌抗原19-9 (CA199)等传统肿瘤标志物的检测已成为诊断各种恶性肿瘤的主要检测手段,然而,这些肿瘤标记物释放到血液中的水平非常低。RDW是常规分析的血液学参数,常用来反映红细胞大小异质性。近年来研究表明,胃癌患者RDW升高与机体炎症反应密切相关,且可作为反映营养状态 ‎[16] 的敏感指标。相关机制可能有:(1) 机体炎症反应导致叶酸、维生素B12等造血原料的缺乏;(2) 机体炎症反应可通过产生炎性介质、影响铁的释放和分布、增强巨噬细胞对红细胞的吞噬作用等方面降低红细胞寿命;(3) 炎症反应会抑制促红细胞生成素的产生 ‎[1] 。据报道,高RDW值与肿瘤坏死因子α、白细胞介素6等炎症因子相关 ‎[17] ‎[18] 。炎症因子通过抑制促红细胞生成素对骨髓造血干细胞的刺激作用、且抑制其抗凋亡作用及在红细胞成熟中的作用。因此,许多未成熟红细胞被释放到外周血液中,从而升高RDW。胃癌患者与高RDW的这种显著关联可能归因于慢性炎症反应和癌症相关性贫血。胃癌可由慢性胃炎进一步发展而来,可见慢性炎症在胃癌的发生中起着至关重要的作用。

然而,本文的不足之处在于:① 纳入的文献均属于回顾性研究,并且文献数量不多;② 不同研究中采用的RDW标准不同,Hirahara ‎[9] 等采用RDW-SD,余文献均采用RDW-CV;③ 各研究RDW的截断值略有不同,可能会导致研究结果准确性欠佳,本文最终未得出RDW的最佳截断值。

5. 结论

综上所述,本研究通过meta分析探讨了胃癌患者术前RDW与其预后的关系,表明术前高RDW可能是中国及日本地区胃癌患者的独立预后因素。医务人员可通过对RDW等血液学参数分层比较,或可更好的指导临床实践。RDW获取方法简便、经济实惠的特性值得临床推广运用,但仍需要更大样本量、前瞻性研究继续探讨RDW对胃癌预后的影响。

NOTES

*第一作者。

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