BCL9 is a Risk Factor of Neck Lymph Nodes Metastasis and Correlated with Immune Cell Infiltration in Papillary Thyroid Carcinoma

Rui Zhang,1,&ast; Zhengwei Gui,2,&ast; Jianguo Zhao,1 Lu Zhao2 1Department of Thyroid and Breast Surgery, Wuhan No. 1 Hospital, Wuhan, 430030, People’s Republic of China; 2Department of Thyroid and Breast Surgery, Tongji Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu Zhao, Department of Thyroid and Breast Surgery, Tongji Hospital affiliated with Tongji Medical College of Huazhong University of Science and Technology, No. 1095 of Jiefang Avenue, Wuhan, 430030, People’s Republic of China, Email luzhao268@outlook.comPurpose: B-cell lymphoma 9 (BCL9), a key transcription co-activator of the Wnt pathway, contributed to tumor progression and metastasis in various tumors, whereas, the role of BCL9 in papillary thyroid cancer (PTC) has not been investigated.Methods: We acquired PTC gene expression data from The Cancer Genome Atlas (TCGA) database. Fifty-nine PTC tissues were applied to validate the clinical significance of BCL9. Cell experiments were applied to investigate the role of BCL9. Bioinformatics analysis was employed to investigate the biological functions of BCL9.Results: We found that BCL9 was higher expressed (P < 0.05) and an independent risk factor for lymph node metastasis (OR = 3.770, P = 0.025), as well as associated with poorer progression-free survival (PFS) (P = 0.049) in PTC. BCL9 knockdown inhibited proliferation and invasion of PTC cells. BCL9 was positively associated with the key genes of Wnt/β-catenin and MAPK pathway by co-expression analysis. GO, KEGG and GSEA analysis showed BCL9 might participated in PPAR, cAMP, and focal adhesion pathway. CIBERSORT analysis found BCL9 was negatively associated with CD8+ T cells and NK cell infiltration and positively with PD-L1 expression.Conclusion: Therefore, BCL9 was associated with lymph node metastasis and shorter PFS of PTC, due to promotion of PTC cell proliferation and invasion, activation of Wnt/β-catenin and MAPK pathway, inhibition of CD8+ T and NK cell infiltration, and promotion of PD-L1 expression.Keywords: BCL9, papillary thyroid cancer, lymph node metastasis, tumor immune microenvironment, tumor-infiltrating immune cells