Prognostic role of indoleamine 2,3-dioxygenase 1 expression in solid tumors: A systematic review and meta-analysis

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 (I² = 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.