Xiyidan Aimaiti,1,2,* Yiyang Wang,1,2,* Dilimulati Ismtula,2,* Yongxiang Li,2 Haotian Ma,2 Junyi Wang,2 Dilraba Elihamu,2 Chenming Guo1,2 

1State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 2Department of Breast Surgery, Center of Digestive and Vascular, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Chenming Guo, Email gcm_xjmu@yeah.net

Introduction: The Bystin gene (BYSL) contributes to cancer development and is a probable therapeutic target in cancer therapy. However, no systematic studies have been conducted on BYSL value in pan-cancer diagnosis, prognosis, and immunology.
Methods: We performed a pan-cancer analysis of BYSL using TCGA, GEO, and other databases to assess its expression, clinical significance, genetic variants, methylation, and immune correlation. Enrichment analysis was applied to predict BYSL-related pathways. We analyzed BYSL protein levels in corresponding breast cancer (BRCA) tissue samples to validate our findings using Western blot assays. A tissue microarray was deployed to verify BYSL expression in BRCA tissues by immunohistochemical staining. Moreover, we comprehensively analyzed the function of BYSL in BRCA initiation and development through CCK-8, transwell invasion, migration assays, and cell scratch assays for migration ability assessment.
Results: Through the study, BYSL was significantly overexpressed in the majority of cancers relative to normal tissues, with different expression patterns at different clinicopathological stages. In most cancer types, BYSL exhibits moderate to high diagnostic value, and overexpressed BYSL represents an independent prognosis factor in patients having BRCA, HNSC, KICH, LIHC, OV, and SARC cancers. Mutations in BYSL are distributed in most cancers and are related to prognosis. Most tumors have elevated levels of m6A methylation compared to normal tissues, while their promoter regions exhibit low levels of methylation. Additionally, BYSL expression displayed a positive correlation with MDSC immune infiltration. Further enrichment analysis showed the involvement of BYSL in important biological processes (BP), In addition, BYSL was overexpressed in BRCA tissues and promoted their proliferation, invasion, and migration compared to matched normal breast tissues.
Discussion: Our study showed that BYSL is an important biological indicator for predicting pan-cancer survival outcomes and immune characteristics and elucidated BYSL expression and role in BRCA, which highlights its therapeutic potential in BRCA.

Keywords: pan-cancer, BYSL, prognosis, methylation, tumor immunity