Zhang Rui, Gui Zhengwei, Zhao Jianguo, Zhao Lu
Department of Thyroid and Breast Surgery, Wuhan No. 1 Hospital, Wuhan, 430030, People's Republic of China.
Department 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.
Int J Gen Med. 2024 Apr 16;17:1451-1466. doi: 10.2147/IJGM.S455846. eCollection 2024.
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.
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.
We found that BCL9 was higher expressed ( < 0.05) and an independent risk factor for lymph node metastasis ( = 3.770, = 0.025), as well as associated with poorer progression-free survival (PFS) ( = 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.
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.
B细胞淋巴瘤9（BCL9）是Wnt信号通路的关键转录共激活因子，在多种肿瘤的进展和转移中发挥作用，然而，BCL9在甲状腺乳头状癌（PTC）中的作用尚未见研究报道。
我们从癌症基因组图谱（TCGA）数据库获取PTC基因表达数据。应用59例PTC组织样本验证BCL9的临床意义。通过细胞实验研究BCL9的作用。采用生物信息学分析探究BCL9的生物学功能。
我们发现BCL9在PTC中高表达（<0.05），是淋巴结转移的独立危险因素（=3.770，=0.025），并且与较差的无进展生存期（PFS）相关（=0.049）。敲低BCL9可抑制PTC细胞的增殖和侵袭。通过共表达分析发现BCL9与Wnt/β-连环蛋白和MAPK信号通路的关键基因呈正相关。GO、KEGG和GSEA分析表明BCL9可能参与PPAR、cAMP和粘着斑信号通路。CIBERSORT分析发现BCL9与CD8 + T细胞和NK细胞浸润呈负相关，与PD-L1表达呈正相关。
因此，BCL9与PTC的淋巴结转移和较短的PFS相关，其机制可能是促进PTC细胞增殖和侵袭、激活Wnt/β-连环蛋白和MAPK信号通路、抑制CD8 + T和NK细胞浸润以及促进PD-L1表达。
