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A Novel Target PCPB1-AS1 Regulates the Treg Infiltration and Serves as a Potential Biomarker for Immunotherapy Response in Lung Adenocarcinoma

Background: Adenocarcinoma (AD) accounts for more than 30% of pulmonary carcinoma with the highest morbidity and mortality in the world. LncRNA regulates various biological processes and shows great potential to become a therapeutic target for AD patients. 
 
Methods: In this research, we combined normal lung tissue sample from the Genotype-Tissue Expression (GTEx) database and AD cohort in the Cancer Genome Atlas (TCGA) project to screen the significant Long non-coding RNAs (lncRNA). Besides, Gene Expression Omnibus (GEO) database and in vitro experiment were applied to subsequent verification. 
 
Findings: After screening, we selected PCPB1-AS1 as the core of follow-up research. Bioinformatic analyses indicated that PCBP1-AS1 specifically influenced intratumoral infiltration of T regulatory cell (Treg), which was verified by the experiments based on our cohort and AD cell lines. Meanwhile, ceRNA network suggested that RORA might be potential target of PCBP1-AS1 to regulate the Treg infiltration. In addition, the prediction of response to immune checkpoint inhibitors (ICI) treatment indicated PCBP1-AS1 expression level was able to become reference for ICIs treatment application. 
 
Interpretation: The compelling evidence demonstrated he rich biological functions of PCBP1-AS1 and its strong possibility to become the potential target for AD therapy. 
 
Funding Statement: National Natural Science Foundation (81672288), Focus on Research and Development Plan in Shandong Province (2018GSF118028) and Natural Science Foundation of Shandong Province (ZR2019PH002). 
 
Declaration of Interests: The authors declare that they have no conflict of interest. 
 
Ethics Approval Statement: This research was approved by Ethics Review Committee of Shandong Provincial Hospital, and was performed based on the Declaration of Helsinki and Good Clinical Practice guidelines, as defined by the International Conference on Harmonisation.