Leptin Receptor Overlapping Transcript (LEPROT) Is Associated with the Tumor Microenvironment and a Prognostic Predictor in Pan-Cancer

Abstract

Background:Leptin receptor overlapping transcript (LEPROT) is reported to be involved in metabolism regulation and energy balance as well as molecular signaling of breast cancer and osteosarcoma. LEPROT is expressed in various tissue and is suggested to be involved in cancer developments but with contradictory roles. The comprehensive knowledge of the effects of LEPROT on cancer development and progression across pan-cancer is still missing.Methods:The expressions of LEPROT in cancers were compared with corresponding normal tissues across pan-cancer types. The relationships between expression and methylation of LEPROT were then demonstrated. The correlations of LEPROT with the tumor microenvironment (TME), including immune checkpoints, tumor immune cells infiltration (TII), and cancer-associated fibroblasts (CAFs), were also investigated. Co-expression analyses and functional enrichments were conducted to suggest the most relevant genes and the mechanisms of the effects in cancers for LEPROT. Finally, the correlations of LEPROT with patient survival and immunotherapy response were explored.Results:LEPROT expression was found to be significantly aberrant in 15/19 (78.9%) cancers compared with corresponding normal tissues; LEPROT was downregulated in 12 cancers and upregulated in three cancers. LEPROT expressions were overall negatively correlated with its methylation alterations. Moreover, LEPROT was profoundly correlated with the TME, including immune checkpoints, TIIs, and CAFs. According to co-expression analyses and functional enrichments, the interactions of LEPROT with the TME may be mediated by the interleukin six signal transducer/the Janus kinase/signal transducers and activators of the transcription signaling pathway. Prognostic values may exist for LEPROT to predict patient survival and immunotherapy response in a context-dependent way.Conclusions:LEPROT affects cancer development by interfering with the TME and regulating inflammatory or immune signals. LEPROT may also serve as a potential prognostic marker or a target in cancer therapy. This is the first study to investigate the roles of LEPROT across pan-cancer.

Extracellular cancer‑associated fibroblasts: A novel subgroup in the cervical cancer microenvironment that exhibits tumor‑promoting roles and prognosis biomarker functions

“…Both LEPROT and LEPR are upregulated in breast cancer tumor tissues, and LEPR has previously been reported to be associated with poor prognosis in breast cancer ( 81 ). LEPROT may communicate with the TME, thereby regulating inflammatory or immune signals, and has been reported both to affect cancer development and to serve as a potential prognostic marker or a therapeutic target in pan-cancer ( 82 ). In numerous types of cancer, such as lung and prostate cancer, PTGS2 is secreted by CAFs, macrophage type 2 cells and tumor cells, and is therefore reported to have pleiotropic and multifaceted roles in terms of both carcinogenesis and cancer cell resistance to chemotherapy and radiotherapy ( 83 ).…”

Single-Nucleotide Polymorphisms in LEP and LEPR Associated With Breast Cancer Risk: Results From a Multicenter Case–Control Study in Chinese Females

“…In contrast, LEPROT was found to activate the JAK/STAT pathway and may facilitate cancer development ( 20 ). A recent study identified an aberrant expression of LEPROT in 78.9% cancers compared with corresponding normal tissues ( 21 ).…”