转移性结直肠癌 (mCRC) 的治疗包括肝转移瘤 (LM) 切除术，但是，没有经过验证的生物标志物可以识别最有可能从该手术中受益的患者。这项荟萃分析旨在评估 CRC 癌症相关基因（即 RAS、BRAF、SMAD4、PIK3CA）中最相关分子改变的影响，作为经 LM 切除手术治疗的 mCRC 患者生存和疾病复发的预后标志物进行了系统性文献综述，以确定报告有关因 CRC LM 接受完全肝切除的患者的生存和/或复发数据的研究，并根据 RAS、BRAF、PIK3CA 和 SMAD4 突变状态进行分层。荟萃分析中汇集了多变量分析的风险比（HR），并结合了针对混杂因素的各种调整策略。检索在多个数据库中进行，包括 MEDLINE (PubMed)、Embase、护理和联合健康文献累积索引 (CINAHL)（EBSCO 主机）和 WHO 全球医学索引，检索时间截至 2022 年 3 月 18 日。荟萃分析、社论、给编辑的信、病例报告、其他原发性癌症的研究、肝脏以外的原发性转移部位的研究、缺乏特定肿瘤学结果变量或遗传数据的研究、非英语语言研究以及省略肝转移切除术中残留疾病数据的研究排除。其余 47 项研究总结在一个描述性表格中，概述了每项研究的关键特征，并以图形方式呈现了最终结果。RAS 突变状态与总生存 (OS) 呈负相关（HR，1.68；95% CI，1.54-1.84）和无复发生存率 (RFS)（HR，1.46；95% CI，1.33-1.61）。 BRAF 与 OS（HR，2.64；95% CI，2.15-3.24）和 RFS（HR，1.89；95% CI，1.32-2.73）和 SMAD4 与 OS（HR，1.93；95% CI）呈负相关。 ，1.56-2.38）和 RFS（HR，1.95；95% CI，1.31-2.91）。对于 PIK3CA，只有三项研究合格，并且与 OS 或 RFS 没有显着相关性。RAS、BRAF 和 SMAD4 与接受结直肠癌根治性肝转移切除术的患者的 OS 和 RFS 呈负相关。由于文献有限，无法得出 PIK3CA 的结论。这些数据支持将 RAS、BRAF 和 SMAD4 突变状态整合到结直肠肝转移的手术决策中。尽管如此，我们必须考虑一些局限性，主要的局限性是评估患者结果的研究结果的汇总，即无病生存期 (DFS) 或 RFS；纳入具有微小残留病和未考虑的潜在混杂因素的患者，例如可切除性定义的可变性、化疗的使用以及生物标志物与切除前和切除后药物治疗之间的潜在相互作用。© 2024 作者。

Treatment of metastatic colorectal cancer (mCRC) includes resection of liver metastases (LM), however, no validated biomarker identifies patients most likely to benefit from this procedure. This meta-analysis aimed to assess the impact of the most relevant molecular alterations in cancer-related genes of CRC (i.e., RAS, BRAF, SMAD4, PIK3CA) as prognostic markers of survival and disease recurrence in patients with mCRC surgically treated by LM resection.A systematic literature review was performed to identify studies reporting data regarding survival and/or recurrence in patients that underwent complete liver resection for CRC LM, stratified according to RAS, BRAF, PIK3CA, and SMAD4 mutational status. Hazard ratios (HRs) from multivariate analyses were pooled in the meta-analysis and various adjustment strategies for confounding factors were combined. The search was conducted in numerous databases, including MEDLINE (PubMed), Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCO host), and WHO Global Index Medicus, through March 18th, 2022. Meta-analyses, editorials, letters to the editor, case reports, studies on other primary cancers, studies with primary metastatic sites other than the liver, studies lacking specific oncological outcome variables or genetic data, non-English language studies, and studies omitting residual disease data from liver metastasectomy were excluded. The remaining 47 studies were summarized in a descriptive table which outlines the key characteristics of each study and final results were graphically presented.RAS mutation status was negatively associated with overall survival (OS) (HR, 1.68; 95% CI, 1.54-1.84) and recurrence free survival (RFS) (HR, 1.46; 95% CI, 1.33-1.61). A negative association was also found for BRAF regarding OS (HR, 2.64; 95% CI, 2.15-3.24) and RFS (HR, 1.89; 95% CI, 1.32-2.73) and SMAD4 regarding OS (HR, 1.93; 95% CI, 1.56-2.38) and RFS (HR, 1.95; 95% CI, 1.31-2.91). For PIK3CA only three studies were eligible and no significant association with either OS or RFS could be highlighted.RAS, BRAF, and SMAD4 are negatively associated with OS and RFS in patients undergoing curative liver metastasectomy from colorectal cancer. No conclusion can be drawn for PIK3CA due to the limited literature availability. These data support the integration of RAS, BRAF, and SMAD4 mutational status in the surgical decision-making for colorectal liver metastasis. Nevertheless, we have to consider several limitations, the major ones being the pooling of results from studies that evaluated patient outcomes as either disease-free survival (DFS) or RFS; the inclusion of patients with minimal residual disease and unconsidered potential confounding factors, such as variability in resectability definitions, chemotherapy use, and a potential interaction between biological markers and pre- and post-resection pharmacological treatments.© 2024 The Authors.