A comprehensive prognostic and immune analysis of LAPTM4B in pan-cancer and Philadelphia chromosomepositive acute lymphoblastic leukemia

Hui Zhou ¹ Yuyao Yi ^1,2 Wei He ^3,4 Li Zheng ^3,4 Yiguo Hu ^3,4* Ting Niu ^5,6,7*

• ¹ Department of Hematology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
• ² Clinic Trial Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
• ³ Department of Thyroid Surgery, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
• ⁴ State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
• ⁵ Department of Hematology, West China Hospital, Sichuan University, Chengdu, China
• ⁶ Collaborative Innovation Center of Biotherapy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
• ⁷ National Facility for Translational Medicine (Sichuan), West China Hospital, Sichuan University, Chengdu, China

Lysosomal-associated protein transmembrane-4 beta (LAPTM4B) protein expression was increased in solid tumors, whereas few studies were performed in hematologic malignancies. We aimed to study the effect of the LAPTM4B gene in pan-cancer and Philadelphia chromosome-positive acute B cell lymphoblastic leukemia (Ph+ B-ALL). The differential expression, diagnosis, prognosis, genetic and epigenetic alterations, tumor microenvironment, stemness, immune infiltration cells, function enrichment, single-cell analysis, and drug response across cancers were conducted based on multiple computational tools. Additionally, Ph+ B-ALL transgenic mouse model with Laptm4b knockout was used to analyze the function of LAPTM4B in vivo. BrdU incorporation method, flow cytometry, and Witte-lock Witte culture were used to evaluate the roles of LAPTM4B in vitro. We identified that LAPTM4B expression was increased in various cancers, with significant associations with clinical outcomes. LAPTM4B expression correlated with DNA and RNA methylation patterns and was associated with drug resistance. It also influenced the tumor immune microenvironment, with implications for immunotherapy response. In leukemia, LAPTM4B was expressed in stem cells and associated with specific subtypes. Knockout of LAPTM4B impeded B-ALL progression in mice and reduced cell proliferation and caused G0/G1 arrest in vitro. Our study elucidated the role LAPTM4B that promoted the development and progression in Ph+ B-ALL. Furthermore, LAPTM4B played a diagnostic, prognostic, and immunological factor.