Search

As an innate feature of human beings, gender differences have an influence on various biological phenotypes, yet it does not attract enough attention in genomics studies. The prognosis of multiple carcinomas usually exhibits a favorable ending for female patients, but the neglect of gender differences can cause serious bias in survival analysis. Enhancer RNAs (eRNAs) are mostly downstream of androgens or estrogen. The present study was aimed to screen eRNAs in patients with non-small-cell lung cancer. The findings revealed that eRNA TBX5-AS1 was expressed differently between female and male patients. Meanwhile, its prognostic significance appeared only in male patients with squamous cell carcinoma (SCC) type. The Gene Set Enrichment Analysis proved that the expression level of TBX5-AS1 increased following the activation of the androgen signaling pathway. In pan-cancer analysis, the prognostic prediction based on gender grouping obtained more meaningful results, and the synergy between TBX5-AS1 and its homologous target was more consistent. Furthermore, immunity variations between sexes prompted us to explore the role that TBX5-AS1 played in tumor microenvironment and immunotherapy. The robust evidence proved that male patients with high expression of TBX5-AS1 possessed a malignant immune microenvironment and urgently needed immune checkpoint inhibitor treatment. In conclusion, TBX5-AS1 may be one of the strongest candidates to predict prognosis for male patients with SCC and provide a reference for immunotherapy.

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.