Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, People's Republic of China.
Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, People's Republic of China; Department of Applied Biology, University for Development Studies, Navrongo, Ghana.
Crit Rev Oncol Hematol. 2018 Jul;127:15-28. doi: 10.1016/j.critrevonc.2018.05.004. Epub 2018 May 16.
The overexpression and mutation of platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) are widespread in cancers and have been recognized as attractive oncologic targets with diverse therapeutic targets. Reports of the overexpression of genes, proteins and mutations of PDGFs/PDGFRs in gastric cancer and their associations with clinicopathological features, Western and Asian patients, as well as prognostic role have shown variable outcomes. This study sought to employ meta-analysis to evaluate PDGFs/PDGFRs status prognostic significance and their association with clinicopathological features of gastric cancer.
A comprehensive search of PubMed database for studies that investigated the overexpression of mRNA/Protein and mutation of PDGFs/PDGFRs in gastric cancer of Western and Asian patients, their prognostic significance and association with clinicopathological characteristics in May, 2017 or earlier was carried out by two reviewers independently. Pooled odd ratios and hazard ratios at 95% confidence intervals were estimated and summarized using fixed-effect and random-effect Mantel-Haenszel models and Inverse Variance models in Review Manager software version 5.3.
Fourteen studies with 16 datasets of 1178 patients were included in meta-analysis. Fourteen studies of 1178 patients with 1446 cases and 7 studies of 1076 patients with 1280 cases were included in meta-analysis of clinicopathological and prognostic significance of high or positive PDGF/PDGFR status respectively. Odd ratio at 95% confidence intervals for different groups of analysis are as follows: males versus females(OR = 1.38, 95% CI: 1.04-1.83, P = 0.03); ≥T2 stage versus T1 stage(OR = 2.06, 95% CI: 1.22-3.49, P = 0.007); nodal metastasis versus no nodal metastasis(OR = 2.78, 95% CI: 1.48-5.22, P = 0.002); TNM stage ≥II versus TNM stage I(OR = 3.55, 95% CI: 1.89-6.69, P<0.0001). Subgroup analysis of the association of PDGF/PDGFR among Western patients(OR = 0.24 95% CI: 0.10-0.58, P = 0.002) and association of PDGFs/PDGFRs gene mutation among gastric cancer patients(OR = 0.15, 95% CI: 0.05-0.45, P = 0.0008) were significant. The association of PDGFs/PDGFRs in young and middle age versus elderly aged, undifferentiated versus well differentiated tumors, large tumor size group(>6 cm) versus small tumor size group(≤6 cm) were insignificant. Subgroup analysis of the association of PDGFs/PDGFRs among Western Asian patients; PDGF/PDGFR mRNA expression and protein expression among gastric cancer patients were insignificant. In addition, PDGF/PDGFR status among gastric cancer patients was insignificant in overall effect analysis PDGF/PDGFR status has shown to predict reduced overall survival(HR = 1.25, 95% CI: 0.49-3.22, P = 0.64) and relapse free survival(HR = 0.93, 95% CI: 0.36-2.41, P = 0.88) insignificantly. Also, overall prognostic effect analysis(HR = 1.07, 95% CI: 0.58-1.96, P = 0.84) was insignificant.
PDGFs/PDGFRs status amongst gastric cancer patients plays a key role in clinical variables and nodal metastasis. These insights might be helpful in providing guidelines for diagnosis, molecular target therapy, and prognosis of gastric cancer.
血小板衍生生长因子（PDGFs）及其受体（PDGFRs）的过表达和突变在癌症中广泛存在，已被认为是具有多种治疗靶点的有吸引力的肿瘤学靶点。报道称，胃癌中 PDGFs/PDGFRs 的基因、蛋白过表达和突变及其与临床病理特征、西方和亚洲患者以及预后的关系存在差异。本研究旨在采用荟萃分析评估 PDGFs/PDGFRs 状态的预后意义及其与胃癌临床病理特征的关系。
两位作者于 2017 年 5 月或更早，对 Pubmed 数据库进行全面检索，以评估西方和亚洲胃癌患者 PDGFs/PDGFRs 的 mRNA/蛋白过表达和突变、其预后意义以及与临床病理特征的关系。使用 Review Manager 软件版本 5.3 中的固定效应和随机效应 Mantel-Haenszel 模型和Inverse Variance 模型，汇总并计算 95%置信区间的合并比值比和风险比。
纳入了 14 项研究，共 16 组数据集，包含 1178 名患者。其中，14 项研究（共 1178 例患者，1446 例病例）用于 PDGF/PDGFR 高表达或阳性状态与临床病理和预后意义的相关性分析，7 项研究（共 1076 例患者，1280 例病例）用于 PDGF/PDGFR 高表达或阳性状态与临床病理特征的相关性分析。不同组分析的比值比（95%置信区间）如下：男性与女性（OR=1.38，95%CI：1.04-1.83，P=0.03）；≥T2 期与 T1 期（OR=2.06，95%CI：1.22-3.49，P=0.007）；有淋巴结转移与无淋巴结转移（OR=2.78，95%CI：1.48-5.22，P=0.002）；TNM 分期≥Ⅱ期与 TNM 分期Ⅰ期（OR=3.55，95%CI：1.89-6.69，P<0.0001）。西方患者中 PDGF/PDGFR 的相关性（OR=0.24，95%CI：0.10-0.58，P=0.002）和胃癌患者中 PDGFs/PDGFRs 基因突变的相关性（OR=0.15，95%CI：0.05-0.45，P=0.0008）的亚组分析有统计学意义。年轻和中年患者与老年患者、低分化肿瘤与高分化肿瘤、肿瘤较大组（>6cm）与肿瘤较小组（≤6cm）之间 PDGFs/PDGFRs 的相关性无统计学意义。西方和亚洲患者中 PDGFs/PDGFRs 的相关性、胃癌患者中 PDGF/PDGFR mRNA 表达和蛋白表达的亚组分析无统计学意义。此外，胃癌患者 PDGF/PDGFR 状态与总体生存（HR=1.25，95%CI：0.49-3.22，P=0.64）和无复发生存（HR=0.93，95%CI：0.36-2.41，P=0.88）的相关性分析无统计学意义。同样，总体预后效应分析（HR=1.07，95%CI：0.58-1.96，P=0.84）也无统计学意义。
胃癌患者的 PDGFs/PDGFRs 状态在临床变量和淋巴结转移中起关键作用。这些发现可能有助于为胃癌的诊断、分子靶向治疗和预后提供指导。
