4785 - Transcriptomic Difference of Thymoma and Thymic Carcinoma

Background

Thymoma and thymic carcinoma (TC) are rare diseases of thymus with relatively good prognosis. Different pathological sub-types of thymoma and TC show clear differences on clinical characteristics, morphology, molecular markers, and prognosis.

Methods

In this study, 26 thymoma and thymic carcinoma patients with most common thymic epithelial tumor subtypes were enrolled, including 2 type A, 6 type AB, 3 type B1, 1 type B1/B2, 5 type B2, 2 type B2/B3, 4 type B3, and 3 type TC patients in total. The frozen tissues of all patients were processed for RNA-seq sequencing.

Results

We used unsupervised clustering to divide all samples into 5 clusters. Four clusters showed clear concordance with pathological subtypes, i.e. cluster AB (5 AB, 1 B1, and 2 B2), cluster B1/B2 (2 B1, 1 B1/B2, and 2B2), cluster B2/B3 (1 B2, 1 B2/B3, and 2B3), and cluster TC (3 TC and 1 A). Only one cluster (1 A, 1 AB, and 2 B3) was labeled as cluster A/AB according to the result of joint clustering analysis with TCGA THYM RNA-seq data. We performed gene function enrichment analysis on highly expressed genes in each cluster. Cluster A showed gene function enrichment on two development related pathways (nervous system development and epithelium development) and cell differentiation. Cluster AB had enriched function of cell proliferation and regulation of cell development. Cluster B1/B2 did not show any enriched functions. Cluster B2/B3 showed gene function enrichment of cell adhesion and regulation of developmental process. CD274 (PD-L1) was also highly expressed in this cluster. Cluster TC had enriched function of several pathways, including cell adhesion, cell migration, cell differentiation, immune system process, immune response, and nervous system development. Moreover, PI3K-Akt signaling pathway, pathway in cancer, and transcriptional misregulation in cancer were also enriched in cluster TC’s highly expressed genes.

Conclusions

Thymic epithelial tumor subtypes show clearly different expression profiles. The highly expressed genes of each subtype relate to development, immune, and cancer related functions. PD-L1 is highly expressed in B2/B3 samples which suggests potential immunotherapy for the subtypes.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Peking Union Medical College Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.