The Cancer Genome Atlas (TCGA) Project defined four prognostic subgroups of Endometrial Cancer (EC): POLE (favorable prognosis), MSI and Copy Number Low (CNL) the intermediate prognosis; and Copy Number High (CNH) unfavorable prognosis.
The aim of the study is to perform a characterization at immune level of the prognostic EC-TCGA groups to identify those cases that could be benefited of immunotherapy.
A total of 48 FFPE EC were retrospectively selected (Ref): POLE (n=6); MSI (n=9); CNL (n=16) and CNH (n=17). Transcriptomic profiling was performed with HTG EdgeSeq Precision Immuno-Oncology Panel (PIO), which interrogates 1392 genes involved in tumor/immune interaction. The estimation of the relative abundance of immune and stromal cellular content and cell types was assigned to the 23 HTG EdgeSeq Reveal software immunophenotyping signatures. DESeq2 R package was used for differential expression analysis. Statistical analysis and data visualization was performed in R version 4.1.2. Clinicopathological information is collected in Table 1.
Unsupervised analysis showed 2 clusters with different prognosis in terms of OS (p=0.0033) and DFS (p=0.00055) (Table 1). Cluster 1 was constituted by 8 MSI, 6 POLE, 14 CNL and 7 CNH while cluster 2 was mainly formed by CNH (10), followed by 1 MSI and 2 CNL. Differential expression analysis resulted in 897 genes between clusters, 400 overexpressed and 497 under expressed in Cluster 1. The 6 most significant genes were TGFB1, BEX1, CDK4, TUBB, RFC4 and TRIP13. In addition, cluster 1 was related with higher PD-1 (p=4.4·10-4), PD-L1(p=9.9·10-6) and CTL4 (p=4·10-4) expression and immune related scores (immune; p=0.00019 and stroma; p=0.00014)
| Cluster 1 | Cluster 2 | Total | ||
| Nº of patients (%) | 35 (73) | 13 (27) | 48 (100) | |
| Histological type (%) | Endometrial | 31 (65) | 9 (19) | 40 (84) |
| Serous | 4 (8) | 4 (8) | 8 (16) | |
| 1 | 17 (35) | 6 (13) | 23 (48) | |
| Grade (%) | 2 | 11 (23) | 3 (6) | 14 (29) |
| 3 | 7 (15) | 4 (8) | 11 (23) | |
| I | 25 (52) | 10 (21) | 35 (73) | |
| Stage (%) | II | 1 (2) | 0 (0) | 1 (2) |
| III | 9 (19) | 3 (6) | 12 (25) | |
| TCGA Group (%) | POLE | 6 (12.5) | 0 (0) | 6 (12.5) |
| MSI | 8 (16.7) | 1 (2.1) | 9 (18.8) | |
| CNL | 14 (29.2) | 2 (4.2) | 16 (33.3) | |
| CNH | 7 (14.6) | 7 (14.6) | 14 (29.2) | |
| Median follow-up [range] months | 89,9 [5 -152] | |||
| Median OS | 101,1 [26-152] | 85,33 [6 -143] | 92,02 [6 - 152] | |
| Median DFS | 101,1 [10-152] | 81,17 [5 - 105] | 89,87 [5 -152] | |
| Relapse (%) | 4/35 (11,4) | 7/13 (53,8) | 11/48 (22,9) | |
| Éxitus (%) | 1/35 (2,9) | 4/13 (30,8) | 5/48 (10,4) |
Cluster stratification suggests implication of immune-related features in classification of EC-patients beyond TCGA subgroups. These findings could be useful in the clinical management of the disease, constituting an open window in the selection of EC patients for immunotherapy