Zhang Haiyan, Li Jing, Zhou Qi
Pharmaceutical Department, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
Front Oncol. 2022 Sep 23;12:954495. doi: 10.3389/fonc.2022.954495. eCollection 2022.
As an emerging immune checkpoint molecule, indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive rate-limiting enzyme in metabolism of tryptophan to kynurenine. The expression of IDO1 affected the prognosis of patients in cancers by regulating the kynurenine pathway, inhibiting the proliferation of T cells. However, the association between IDO1 and solid tumor prognosis was controversial. To further investigate the role of IDO1 expression in solid tumors, we conducted the systematic review and meta-analysis.
We searched the Web of Science, PubMed, Embase, and Cochrane Library databases and China National Knowledge Infrastructure (CNKI) to identify studies evaluating the prognostic value of IDO1 in solid tumors. Overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) were extracted as the outcome. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated by using the fixed-effect/random-effect model, while heterogeneity, publication bias, and sensitivity between studies were also analyzed.
Eighteen studies with 2,168 patients were included in this systematic review and meta-analysis. The results indicated that the high expression of IDO1 was associated with a shorter OS (n = 1926, HR = 1.60, 95% CI: 1.22-2.11, P = 0.001) and DFS (n = 327, HR = 2.65, 95% CI: 1.52-4.63, P = 0.001), while it was uncorrelated with PFS (n = 428, HR = 1.76, 95% CI: 0.99-3.14, P = 0.240). There was significant heterogeneity between studies on OS (I = 77.8%, P < 0.001). Subgroup analysis showed that age, gender, tumor type, follow-up period, and study quality were possible reasons for high heterogeneity. The result of the trim-and-fill method indicated that publication bias for OS had no impact on our results. Egger's test suggested no publication bias for PFS (P = 0.553) and DFS (P = 0.273). Furthermore, sensitivity analysis indicated the result was stable.
High expression of IDO1 was associated with poor clinical outcomes, indicating that it could be a potential prognostic marker in various cancer types.
作为一种新兴的免疫检查点分子，吲哚胺2,3-双加氧酶1（IDO1）是色氨酸代谢为犬尿氨酸过程中的一种免疫抑制限速酶。IDO1的表达通过调节犬尿氨酸途径、抑制T细胞增殖影响癌症患者的预后。然而，IDO1与实体瘤预后之间的关联存在争议。为进一步探究IDO1表达在实体瘤中的作用，我们进行了系统评价和荟萃分析。
我们检索了Web of Science、PubMed、Embase和Cochrane图书馆数据库以及中国知网，以识别评估IDO1在实体瘤中预后价值的研究。提取总生存期（OS）、无进展生存期（PFS）和无病生存期（DFS）作为结局指标。采用固定效应/随机效应模型计算合并风险比（HRs）及其95%置信区间（CIs），同时分析研究间的异质性、发表偏倚和敏感性。
本系统评价和荟萃分析纳入了18项研究，共2168例患者。结果表明，IDO1高表达与较短的OS（n = 1926，HR = 1.60，95%CI：1.22 - 2.11，P = 0.001）和DFS（n = 327，HR = 2.65，95%CI：1.52 - 4.63，P = 0.001）相关，而与PFS无关（n = 428，HR = 1.76，95%CI：0.99 - 3.14，P = 0.240）。关于OS的研究间存在显著异质性（I² = 77.8%，P < 0.001）。亚组分析表明，年龄、性别、肿瘤类型、随访时间和研究质量可能是异质性高的原因。剪补法结果表明，OS的发表偏倚对我们的结果无影响。Egger检验提示PFS（P = 0.553）和DFS（P = 0.273）无发表偏倚。此外，敏感性分析表明结果稳定。
IDO1高表达与不良临床结局相关，表明它可能是多种癌症类型中的一种潜在预后标志物。
