ADCY4 promotes brain metastasis in small cell lung cancer and is associated with energy metabolism
Yidan Sun,
Yixun Chen,
Xin Zhang,
Dan Yi,
Fanming Kong,
Linlin Zhao,
Dongying Liao,
Lei Chen,
Qianqian Ma,
Ziheng Wang
Affiliations
Yidan Sun
Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300382, China
Yixun Chen
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
Xin Zhang
Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300382, China
Dan Yi
Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300382, China
Fanming Kong
Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300382, China
Linlin Zhao
Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300382, China
Dongying Liao
Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300382, China
Lei Chen
Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300382, China
Qianqian Ma
Affiliated Women's Hospital of Jiangnan University Wuxi, Jiangsu, China; Corresponding author. Affiliated Women's Hospital of Jiangnan University Wuxi, Jiangsu, China.
Ziheng Wang
Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China; Department of Clinical Bio-bank, Affiliated Hospital of Nantong University, Jiangsu, China; Corresponding authorCentre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China
Brain metastasis (BMs) in small cell lung cancer (SCLC) has a very poor prognosis. This study combined WGCNA with the mfuzz algorithm to identify potential biomarkers in the peripheral blood of patients with BMs. By comparing the significantly differentially expressed genes present in BMs samples, we identified ADCY4 as a target for further study. Expression of ADCY4 was used to cluster mfuzz expression pattern, and 28 hub genes for functional enrichment. PPI network analysis were obtained by comparing with differentially expressed genes in BMs. GABRE, NFE4 and LMOD2 are highly expressed in patients with BMs and have a good diagnostic effect. Immunoinfiltration analysis showed that SCLC patients with BMs may be associated with memory B cells, Tregs, NK cell activation, macrophage M0 and dendritic cell activation. prophytic was used to investigate the ADCY4-mediated anti-tumor drug response. In conclusion, ADCY4 can be used as a promising candidate biomarker for predicting BMs, molecular and immune features in SCLC. PCR showed that ADCY4 expression was increased in NCI–H209 and NCI–H526 SCLC cell lines. In vitro experiments confirmed that the expression of ADCY4 was significantly decreased after anti-PD1 antibody treatment, while the expression of energy metabolism factors were significantly different. This study reveals a potential mechanism by which ADCY4 mediates poor prognosis through energy metabolism -related pathways in SCLC.
