Background Tissue inhibitor of metalloproteinase 1 (TIMP-1) has recently been shown to be dependent on or independent of Matrix metalloproteinases (MMPs) in its roles in tumorigenesis and progression. This appreciation has prompted various studies assessing the prognostic value of TIMP-1 in patients with gastrointestinal cancer, however, the conclusions were still inconsistent. The aim of this study was to assess the prognostic value of TIMP-1-immunohistochemistry (IHC) staining and pretreatment serum/plasma TIMP-1 level in gastrointestinal cancer survival as well as the association between TIMP-1 and clinicopathologic features. Methods The meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO; Registration NO. CRD42020185407) and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. A highly sensitive literature search was performed in electronic databases including PubMed, EMBASE and the Cochrane Library. Heterogeneity analysis was conducted using both chi-square-based Q statistics and the I2 test. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to assess the prognostic value of TIMP-1 using the fixed-effects model. Odds ratios (ORs) with 95% CIs were calculated to evaluate the associations between TIMP-1 and clinicopathological characteristics. The meta-analysis was conducted using STATA 12.0 software. Results A total of 3,958 patients from twenty-two studies were included in the meta-analysis. Elevated TIMP-1 levels were significantly associated with poor survival in gastrointestinal cancer (TIMP-1-IHC staining: HR = 2.04, 95% CI [1.59–2.61], I2 = 35.7%, PQ = 0.156; pretreatment serum/plasma TIMP-1 levels: HR = 2.02, 95% CI [1.80–2.28], I2 = 0%, PQ = 0.630). Moreover, clinicopathological parameter data analysis showed that elevated TIMP-1 levels were significantly associated with lymph node metastasis (N1/N2/N3 vs N0: OR = 2.92, 95% CI [1.95–4.38]) and higher TNM stages (III/IV vs I/II: OR = 2.73, 95% CI [1.23–6.04]). Conclusion Both TIMP-1-positive IHC staining and high serum/plasma TIMP-1 levels are poor prognostic factors for the survival of gastrointestinal cancer. In addition, TIMP-1 overexpression was correlated with more advanced clinicopathological features.

中文翻译：

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金属蛋白酶-1 (TIMP-1) 组织抑制剂作为胃肠道癌的预后生物标志物：荟萃分析

背景 金属蛋白酶组织抑制剂 1 (TIMP-1) 最近已被证明在肿瘤发生和进展中的作用依赖或不依赖于基质金属蛋白酶 (MMP)。这种认识促使各种研究评估 TIMP-1 在胃肠道癌患者中的预后价值，但结论仍然不一致。本研究的目的是评估 TIMP-1-免疫组织化学 (IHC) 染色和预处理血清/血浆 TIMP-1 水平在胃肠道癌存活中的预后价值，以及 TIMP-1 与临床病理学特征之间的关联。方法 荟萃分析在国际系统评价前瞻性注册库（PROSPERO；注册号：CRD42020185407）并遵循系统评价和荟萃分析的首选报告项目（PRISMA）声明。在 PubMed、EMBASE 和 Cochrane 图书馆等电子数据库中进行了高度敏感的文献检索。使用基于卡方的 Q 统计量和 I2 检验进行异质性分析。使用固定效应模型计算具有 95% 置信区间 (CI) 的汇总风险比 (HR) 以评估 TIMP-1 的预后价值。计算具有 95% CI 的优势比 (OR) 以评估 TIMP-1 与临床病理学特征之间的关联。Meta分析使用STATA 12.0软件进行。结果 共有来自 22 项研究的 3,958 名患者被纳入荟萃分析。升高的 TIMP-1 水平与胃肠癌的不良生存率显着相关（TIMP-1-IHC 染色：HR = 2.04, 95% CI [1.59–2.61], I2 = 35.7%, PQ = 0.156；预处理血清/血浆 TIMP- 1 级：HR = 2.02, 95% CI [1.80–2.28], I2 = 0%, PQ = 0.630)。此外，临床病理参数数据分析显示，TIMP-1 水平升高与淋巴结转移显着相关（N1/N2/N3 vs N0：OR = 2.92, 95% CI [1.95–4.38]）和更高的 TNM 分期（III/IV与 I/II：OR = 2.73, 95% CI [1.23–6.04]）。结论 TIMP-1阳性IHC染色和高血清/血浆TIMP-1水平是胃肠道癌生存的不良预后因素。此外，TIMP-1 过表达与更高级的临床病理学特征相关。61]，I2 = 35.7%，PQ = 0.156；预处理血清/血浆 TIMP-1 水平：HR = 2.02, 95% CI [1.80–2.28], I2 = 0%, PQ = 0.630)。此外，临床病理参数数据分析显示，TIMP-1 水平升高与淋巴结转移显着相关（N1/N2/N3 vs N0：OR = 2.92, 95% CI [1.95–4.38]）和更高的 TNM 分期（III/IV与 I/II：OR = 2.73, 95% CI [1.23–6.04]）。结论 TIMP-1阳性IHC染色和高血清/血浆TIMP-1水平是胃肠道癌生存的不良预后因素。此外，TIMP-1 过表达与更高级的临床病理学特征相关。61]，I2 = 35.7%，PQ = 0.156；预处理血清/血浆 TIMP-1 水平：HR = 2.02, 95% CI [1.80–2.28], I2 = 0%, PQ = 0.630)。此外，临床病理参数数据分析显示，TIMP-1 水平升高与淋巴结转移显着相关（N1/N2/N3 vs N0：OR = 2.92, 95% CI [1.95–4.38]）和更高的 TNM 分期（III/IV与 I/II：OR = 2.73, 95% CI [1.23–6.04]）。结论 TIMP-1阳性IHC染色和高血清/血浆TIMP-1水平是胃肠道癌生存的不良预后因素。此外，TIMP-1 过表达与更高级的临床病理学特征相关。临床病理参数数据分析显示，TIMP-1 水平升高与淋巴结转移显着相关（N1/N2/N3 vs N0：OR = 2.92, 95% CI [1.95–4.38]）和更高的 TNM 分期（III/IV vs I /II：OR = 2.73，95% CI [1.23–6.04]）。结论 TIMP-1阳性IHC染色和高血清/血浆TIMP-1水平是胃肠道癌生存的不良预后因素。此外，TIMP-1 过表达与更高级的临床病理学特征相关。临床病理参数数据分析显示，TIMP-1 水平升高与淋巴结转移显着相关（N1/N2/N3 vs N0：OR = 2.92, 95% CI [1.95–4.38]）和更高的 TNM 分期（III/IV vs I /II：OR = 2.73，95% CI [1.23–6.04]）。结论 TIMP-1阳性IHC染色和高血清/血浆TIMP-1水平是胃肠道癌生存的不良预后因素。此外，TIMP-1 过表达与更高级的临床病理学特征相关。