A genomic instability-associated lncRNA signature for predicting prognosis and biomarkers in lung adenocarcinoma.

Genomic instability (GI) was associated with tumorigenesis. However, GI-related lncRNA signature (GILncSig) in lung adenocarcinoma (LUAD) is still unknown. In this study, the lncRNA expression data, somatic mutation information and clinical survival information of LUAD were downloaded from The Cancer Genome Atlas (TCGA) and performed differential analysis. Functional and prognosis analysis revealed that multiple GI-related pathways were enriched. By using univariate and multivariate Cox regression analysis, 5 GI-associated lncRNAs (AC012085.2, FAM83A-AS1, MIR223HG, MIR193BHG, LINC01116) were identified and used to construct a GILncSig model. Mutation burden analysis indicated that the high-risk GI group had much higher somatic mutation count and the risk score constructed by the 5 GI-associated lncRNAs was an independent predictor for overall survival (OS) (P < 0.05). Overall, our study provides valuable insights into the involvement of GI-associated lncRNAs in LUAD and highlights their potential as therapeutic targets.

Molecular Characterization Clinical and Immunotherapeutic Characteristics of m5C Regulator NOP2 Across 33 Cancer Types.

Background: Recent studies have identified that RNA 5-methylcytosine (m5C) is a wide-spread epigenetic modification in tumorigenesis. However, the clinical and immunotherapeutic values of m5C regulator NOP2 in 33 cancers remain unclear. Methods: The mRNA expression data and clinical data of 33 cancers were downloaded from The Cancer Genome Atlas (TCGA) database. The immunotherapy data including GSE67501, GSE78220, GSE35640, and IMvigor210 were downloaded from the Gene Expression Omnibus (GEO) database and the website based on the Creative Commons 3.0 license (http://research-pub.Gene.com/imvigor210corebiologies). The expression, survival, clinical parameters, tumor mutation burden (TMB), microsatellite instability (MSI), and tumor microenvironment (TME) were evaluated. Finally, the relationship between NOP2 and immunotherapy response was further explored. Results: NOP2 was significantly upregulated in most cancers, and high NOP2 expression was associated with poor prognosis. TMB, MSI, and NOP2 activities were involved in the dysregulation of NOP2. NOP2 was closely associated with immune cell infiltration, immune modulators, and immunotherapeutic inactivation. Conclusions: We comprehensively explored the clinical and immunotherapeutic values of NOP2 in cancers, providing evidence regarding the function of NOP2 and its role in clinical treatment.

5-methylcytosine RNA methylation regulators affect prognosis and tumor microenvironment in lung adenocarcinoma.

Background: Accumulating evidence has shown that 5-methylcytosinec (m5C) RNA methylation plays an essential role in tumorigenesis. However, the roles of m5C regulators in the prognosis, tumor microenvironment (TME), and immunotherapy responses of lung adenocarcinoma (LUAD) have not been fully analyzed. Methods: Based on 14 m5C RNA regulators, we evaluated the m5C RNA modification patterns in patients with LUAD (n=594) in The Cancer Genome Atlas (TCGA). Unsupervised clustering analysis was performed to confirm distinct m5C modification patterns. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to investigate the biological functions of differentially expressed genes (DEGs) among different m5C RNA modification patterns. An m5C signature (m5Csig) was constructed using least absolute shrinkage and selection operator (LASSO) algorithms. The GSE72094 cohort (n=442) from the Gene Expression Omnibus (GEO) was used to validate m5Csig. A receiver operating characteristic (ROC) model was constructed to evaluate the sensitivity and specificity of m5Csig. Tumor-infiltrating immune cells (TIICs) between the high- and low-risk groups were estimated using the Cell Type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm. Results: We identified 3 m5C RNA modification clusters. Overall survival (OS) differed among the 3 clusters. The m5Csig, including TRDMT1, NSUN1, NSUN4, NSUN7, and ALYREF, was constructed to classify patients with LUAD into high- and low-risk groups. The high-risk group, with more immune cell infiltration, had a significantly poorer OS than that the low-risk group, which was associated with better response to immune checkpoint blockade therapy. Conclusions: The present study revealed that m5C RNA regulators play a significant role in TME regulation in LUAD. The m5Csig can predict the prognosis of patients with LUAD and might provide novel strategies for tumor immunotherapy.

LKB1 expression and the prognosis of lung cancer: A meta-analysis.

BACKGROUND: In the past few decades, many lines of evidence implicate the importance of liver kinase B1 (LKB1) as a tumor suppressor gene in the development and progression of solid tumours. However, the prognostic and clinicopathological value of LKB1 in patients with lung cancer are controversial. This article aimed to investigate the latest evidence on this question. METHODS: A systematic literature searched in the PubMed, Web of Science, Embase, Cochrane library, Scopus until September 20, 2020. The association between overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS), clinicopathological features and LKB1 were analysed by meta-analysis. RESULTS: Eleven studies including 1507 patients were included in this meta-analysis. The pooled results revealed that low LKB1 expression was significantly associated with poor overall survival (OS) (HR = 1.67, 95% CI: 1.07-2.60, P = .024) in lung cancer. However, no association was found between LKB1 expression and DFS/PFS (HR = 1.29, 95% CI: 0.70-2.39, P = .410). Pooled results showed that low LKB1 expression was associated with histological differentiation (poor vs moderate or well, OR = 4.135, 95% CI:2.524-6.774, P < .001), nodal metastasis (absent vs present, OR = 0.503, 95% CI: 0.303-0.835, P = .008) and smoking (yes vs no, OR = 1.765, 95% CI: 1.120-2.782, P = .014). CONCLUSION: These results suggest that low expression of LKB1 can be considered as a unfavorable prognostic biomarker for human lung cancer, which should be further researched.

Prognostic and clinicopathological value of PD-L2 in lung cancer: A meta-analysis.

OBJECTIVE: The prognostic role of programmed death ligand-2 (PD-L2) expression in lung cancer has been widely studied, however, the results are controversial. Accordingly, we investigated the prognostic and clinicopathological value of PD-L2 in patients with lung cancer in this meta-analysis. METHODS: Relevant studies were systematically searched in the PubMed, Web of Science, EMBASE, ClinicalTrials.gov., Scopus, and Cochrane Library until July 10, 2020. The hazard ratio (HR), odds ratio (OR), and their corresponding 95% confidence intervals (CIs) were calculated. RESULTS: Thirteen studies with 3107 participants were included. High PD-L2 expression was associated with poor overall survival (OS) (HR 1.248, 95% CI: 1.071-1.455, p = 0.004) and worse disease-free survival (DFS)/progression-free survival (PFS)/relapse-free survival (RFS) (HR 1.224, 95% CI: 1.058-1.417, p = 0.007) in lung cancer. Furthermore, unfavorable OS was found in lung adenocarcinoma (HR 1.349, 95% CI: 1.051-1.731, p = 0.019), but not in other pathological types (HR 1.192, 95% CI: 0.982-1.447 p = 0.076) with higher PD-L2 expression in our subgroup analysis. Concerning the clinicopathological characteristics, high PD-L2 expression was associated with smoking (OR 0.725, 95% CI: 0.591-0.890, p = 0.002) and PD-L1 (OR 1.607, 95% CI:1.115-2.314, p = 0.011) and vascular invasion (OR 1.500, 95% CI: 1.022-2.203, p = 0.039). CONCLUSION: PD-L2 overexpression might predict a poor prognosis in lung cancer patients after surgery. PD-L2 expression might be a potential biomarker for PD-1/PD-L1-targeted immunotherapy in lung cancer, which should be investigated in future studies.

Prognostic and clinicopathological utility of PD-L2 expression in patients with digestive system cancers: A meta-analysis.

OBJECTIVE: Programmed death ligand-2 (PD-L2)has been detected in various cancers. However, its prognostic value in digestive system cancers (DSCs) remains unclear. Accordingly, this meta-analysis investigated the prognostic and clinicopathological utility of PD-L2 in patients with DSCs. METHODS: We systematically searched PubMed, EMBASE, Web of Science, ClinicalTrials.gov., Scopus, and Cochrane Library databases for eligible studies up to April 30, 2020. The hazard ratio (HR), odds ratio (OR), and corresponding 95% confidence interval (CI) of the outcomes were calculated. RESULTS: Twenty two studies with 4886 patients were included in this meta-analysis. The pooled results showed that PD-L2 overexpression was significantly associated with poor overall survival (OS) (HR 1.470, 95% CI: 1.252-1.728, p < 0.001) and worse disease-free survival (DFS) (HR1.598, 95% CI: 1.398-1.826, p < 0.001). Subgroup analysis revealed that elevated PD-L2 was a significant prognostic indicator of worse OS in hepatocellular carcinoma (HR 1.703, 95% CI: 1.456-1.991, p < 0.001) and colorectal cancer (HR 3.811, 95% CI: 1.718-8.454, p = 0.001). Concerning clinicopathologic factors, PD-L2 overexpression was associated with lymphatic metastasis (OR 1.394., 95% CI: 1.101-1.764, p = 0.006), tumor metastasis (OR 1.599, 95% CI: 1.072-2.383, p = 0.021), and the histopathological stage (OR 0.704, 95% CI: 0.566-0.875, p = 0.002). CONCLUSION: PD-L2 overexpression in DSCs after surgery might predict a poor prognosis, especially in hepatocellular carcinoma and colorectal cancer. Larger patient cohorts are needed to validate its prognostic role.