Prognostic value and immune infiltration of a novel stromal/immune score-related P2RY12 in lung adenocarcinoma microenvironment.

Increasing evidence highlights the clinical implications of P2RY12 that belongs to the family of G-protein coupled receptors in carcinogenesis. Here, this study was designed to explore the associations between P2RY12 and tumor immune microenvironment of lung adenocarcinoma (LUAD). Based on 352 LUAD samples from The Cancer Genome Atlas (TCGA), stromal and immune scores of each sample were estimated by ESTIMATE algorithm. Differential expression analysis was presented between stromal/immune high- and low-score groups. Protein-protein interaction (PPI) was then constructed by STRING database. Univariate and multivariate Cox regression analysis was utilized to screen prognosis-related factors. Co-expressed genes of P2RY12 were analyzed, followed by functional enrichment analysis. Furthermore, the correlation between P2RY12 and immune cell infiltrations was estimated using the TIMER database. P2RY12 expression was validated between 37 pairs of LUAD and normal tissues using RT-qPCR and immunohistochemistry. After overexpressing P2RY12, the proliferation and migration of A549 cells was detected by CCK-8 and scratch test. 145 up- and 102 down-regulated stromal- and immune-related mRNAs were identified for LUAD. Based on 145 up-regulated mRNAs, a PPI network was conducted, consisting of 95 nodes and 210 relationship pairs. Ten hub genes were then identified. Among them, CCR8, CNR2, CXCR5, GPR18, GPR31 and P2RY12 were in association with overall survival of patients with LUAD. After adjusting other variables, P2RY12 expression was an independent prognostic factor for LUAD. 288 co-expressed genes of P2RY12 were determined and these co-expressed genes were primarily involved in immune-related biological processes or pathways. Moreover, P2RY12 was significantly correlated with M2 macrophage and dendritic cell infiltration. After validation, P2RY12 expression was significantly decreased in LUAD than normal tissues. Its overexpression distinctly suppressed proliferation and migration of A549 cells. Our findings suggest that P2RY12 is an immune infiltration-related prognostic marker for LUAD.

Yu L ，Cao S ，Li J ，Han B ，Zhong H ，Zhong R ... -  《-》

Heat shock factor 5 correlated with immune infiltration serves as a prognostic biomarker in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the predominant subtype of lung cancer with a relatively poor prognosis. The dramatic improvements of new immunotherapy strategies have shown promising results in lung cancer patients. This study aimed to elucidate the functions of immune-associated genes in LUAD prognosis and pathogenesis by analyzing public databases. We obtained expression profiles of LUAD patients from The Cancer Genome Atlas (TCGA) database and applied the ESTIMATE algorithm to calculate immune scores and stromal scores. A series of microenvironment-related genes with prognostic value was then identified. Of note, heat shock factor 5 (HSF5) was found to be decreased in LUAD patients and positively correlated with overall survival, which was further confirmed in the Gene Expression Omnibus (GEO) database. Moreover, Gene Ontology (GO) analysis based on the correlated genes of HSF5 demonstrated that HSF5 expression was significantly associated with the immune response and inflammatory activities. Based on the Tumor IMmune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA) datasets, HSF5 expression showed strong correlations with various immune cell infiltration and diverse immune marker sets. These findings suggest that HSF5 can be used as a promising biomarker for determining prognosis and immune infiltration in LUAD patients.

Aizemaiti R ，Wu Z ，Tang J ，Yan H ，Lv X ... -  《International Journal of Medical Sciences》

Increased expression of TTC21A in lung adenocarcinoma infers favorable prognosis and high immune infiltrating level.

Lung adenocarcinoma (LUAD) is a crucial pathological type of lung cancer. Immune-infiltration of the tumor microenvironment positively associated with overall survival in LUAD. TTC21A is a gene has not reported in cancer, and the mechanism behind it is still unclear. Our study assesses TTC21A role in LUAD, via TCGA data. GEPIA was utilized to analyze the expression of TTC21A in LUAD. We evaluated the influence of TTC21A on survival of LUAD patients by survival module. Then, data sets of LUAD were downloaded from TCGA. The correlations between clinical information and TTC21A expression were analyzed using logistic regression. Clinicopathologic characteristics associated with overall survival in TCGA patients using Cox regression. In addition, we explored the correlation between TTC21A and cancer immune infiltrates using CIBERSORT and "Correlation" module of GEPIA. The univariate analysis using logistic regression, wherein TTC21A expression served as a categorical dependent variable (with a median expression value of 2.5), indicated that increased TTC21A expression is significantly correlated with pathological stage, tumor status and lymph nodes. Moreover, multivariate analysis revealed that the up-regulated TTC21A expression, negative results of pathological stage and distant metastasis are independent prognostic factors for good prognosis. Specifically, a positive correlation between increased TTC21A expression and immune infiltrating level of B cells, Neutrophils, Mast cells and T cells was established using CIBERSORT analysis. Furthermore, we confirmed it in "correlation" module of GEPIA. Together with all these findings, increased TTC21A expression correlates with favorable prognosis and increased proportion of immune cells, such as B cells, Neutrophils, Mast cells and T cells in LUAD. These conclusions indicate that TTC21A could serve as a potential biomarker to assess prognosis and immune infiltration level in LUAD.

Wang W ，Ren S ，Wang Z ，Zhang C ，Huang J ... -  《-》

Immune profile of the tumor microenvironment and the identification of a four-gene signature for lung adenocarcinoma.

Fan T ，Zhu M ，Wang L ，Liu Y ，Tian H ，Zheng Y ，Tan F ，Sun N ，Li C ，He J ... -  《Aging-US》

FAM207BP, a pseudogene-derived lncRNA, facilitates proliferation, migration and invasion of lung adenocarcinoma cells and acts as an immune-related prognostic factor.

This study aimed to characterize the functions of pseudogene-derived long non-coding RNA (lncRNA) FAM207BP in lung adenocarcinoma (LUAD). Through the Cancer Genome Atlas (TCGA)-Genotype Tissue Expression (GTEx) database, FAM207BP expression was detected in LUAD and normal tissues. Overall survival (OS) and disease-free survival (DFS) analysis was presented using log-rank test or univariate Cox regression analysis. The relationships between FAM207BP expression and clinical features were analyzed. FAM207BP expression was validated in LUAD tissues and cells using RT-qPCR. Cell viability of LUAD cells was evaluated after silencing or overexpressing FAM207BP. Furthermore, migrated and invasive abilities were examined by Transwell and scratch assays. The correlation between FAM207BP expression and the immune infiltration levels was analyzed. Gene Set Enrichment Analysis (GSEA) was performed for high- and low-expression of FAM207BP using C2 collection in the Molecular Signatures Database (MSigDB) database. FAM207BP expression was distinctly higher in LUAD than normal tissues. Patients with its high expression indicated worse OS and DFS time. FAM207BP expression was significantly related to gender. RT-qPCR results confirmed that FAM207BP was significantly highly expressed in LUAD tissues and cells. Knockdown of FAM207BP distinctly suppressed cellular viability, migration and invasion for LUAD cells. Also, its expression was negatively related to B cell infiltration levels. GSEA results indicated that high FAM207BP expression was involved in regulation of gene expression. Its low expression was related to immune response. Pseudogene-derived lncRNA FAM207BP could induce proliferation and migration of LUAD cells, which could act as an immune-related prognostic factor.

Yu L ，Qiao R ，Xu J ，Han B ，Zhong R ... -  《-》