Fibroblast-derived LPP as a biomarker for treatment response and therapeutic target in gastric cancer

Autor: Hao Wang, Jing Wu, Ruoyu Ling, Fengping Li, Qingbin Yang, Jiayong He, Xuetao Lei, Chaorui Wu, Guofan Zhang, Boyang Zheng, Yanmei Peng, Yihao Zhang, Hao Chen, Gengtai Ye, Guoxin Li
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Molecular Therapy: Oncolytics, Vol 24, Iss , Pp 547-560 (2022)
Druh dokumentu: article
ISSN: 2372-7705
DOI: 10.1016/j.omto.2022.01.008
Popis: Association of tumor microenvironment and immune checkpoint (e.g., PD-L1) is important for immune escape, impacting chemotherapy and immunotherapy efficacy. We aimed to investigate biomarkers and therapeutic targets against treatment resistance in gastric cancer. Abundances of tumor-infiltrating immune cells were estimated in multiple datasets. Three patient subgroups (A, B, and C) were identified based on seven types of PD-L1- and IFN-γ-associated immune cells. Patients yielded increased prognosis from subgroup A to C (p = 0.027). Subgroup A was characterized by high activated CD4+ memory T cell infiltration, while more resting CD4+ memory T cells were in subgroup C. Further, a risk score was developed for prognostication. Lipoma preferred partner (LPP), as the hub gene in subgroup-related regulatory network, was upregulated (p < 0.01) and was associated with high risk score (p < 0.001) and poor survival (p < 0.05). Bioinformatics analyses and experiments found that LPP expressed restrictively in fibroblasts and associated with activated CD4+ memory T cell infiltration and tumor growth. High-LPP patients yielded fewer benefits from chemotherapy or immunotherapy, compared with the low-LPP group. We finally identified 28 compounds as sensitive drugs for high-LPP patients. Our findings suggested LPP might be a biomarker for treatment response and therapeutic target in gastric cancer.
Databáze: Directory of Open Access Journals