Polo like kinase 1 expression in cervical cancer tissues generated from multiple detection methods.

BACKGROUND: Existing studies of PLK1 in cervical cancer had several flaws. The methods adopted by those studies of detecting PLK1 expression in cervical cancer were single and there lacks comprehensive evaluation of the clinico-pathological significance of PLK1 in cervical cancer. METHODS: A total of 303 cervical tissue samples were collected for in-house tissue microarrays. Immunohistochemistry was performed for evaluating PLK1 expression between cervical cancer (including cervical squamous cell carcinoma (CESC) and cervical adenocarcinoma) and non-cancer samples. The Expression Atlas database was searched for querying PLK1 expression in different cervical cancer cell lines and different tissues in the context of pan-cancer. Standard mean difference (SMD) was calculated and the summarized receiver's operating characteristics (SROC) curves were plotted for integrated tissue microarrays, exterior high-throughput microarrays and RNA sequencing data as further verification. The effect of PLK1 expression on the overall survival, disease-free survival and event-free survival of cervical cancer patients was analyzed through Kaplan Meier survival curves for cervical cancer patients from RNA-seq and GSE44001 datasets. The gene mutation and alteration status of PLK1 in cervical cancer was inspected in COSMIC and cBioPortal databases. Functional enrichment analysis was performed for genes correlated with PLK1 from aggregated RNA-seq and microarrays. RESULTS: A total of 963 cervical cancer samples and 178 non-cancer samples were collected from in-house tissue microarrays and exterior microarrays and RNA-seq datasets. The combined expression analysis supported overexpression of PLK1 in CESC, cervical adenocarcinoma and all types of cervical cancer (SMD = 1.59, 95%CI [0.56-2.63]; SMD = 2.99, 95%CI [0.75-5.24]; SMD = 1.57, 95% CI [0.85-2.29]) and the significant power of PLK1 expression in distinguishing CESC or all types of cervical cancer samples from non-cancer samples (AUC = 0.94, AUC = 0.92). Kaplan-Meier survival curves showed that the event-free survival rate of cervical cancer patients with higher expression of PLK1 was shorter than that of patients with lower PLK1 (HR = 2.020, P = 0.0197). Genetic alteration of PLK1 including missense mutation and mRNA low occurred in 6% of cervical cancer samples profiled in mRNA expression. Genes positively or negatively correlated with PLK1 were mainly assembled in pathways such as DNA replication, cell cycle, mismatch repair, Ras signaling pathway, melanoma, EGFR tyrosine kinase inhibitor resistance and homologous recombination (P < 0.05). CONCLUSIONS: Here, we provided sufficient evidence of PLK1 overexpression in cervical cancer. The overexpression of PLK1 in cervical cancer and the contributory effect of it on clinical progression indicated the hopeful prospect of PLK1 as a biomarker for cervical cancer.

Clinical value of microRNA-198-5p downregulation in lung adenocarcinoma and its potential pathways.

Lung adenocarcinoma (LUAD), the main subtype of non-small cell lung cancer, is known to be regulated by various microRNAs (miRs/miRNAs); however, the role of miR-198-5p in LUAD has not been clarified. In the present study, the clinical value of miR-198-5p in LUAD and its potential molecular mechanism was evaluated. miR-198-5p expression was examined by reverse transcription-quantitative PCR (RT-qPCR) in 101 paired LUAD and adjacent normal lung tissues. Subsequently, the miR-198-5p expression level was determined from microarray data from the Gene Expression Omnibus, ArrayExpress and by meta-analyses. Furthermore, the target mRNAs of miR-198-5p from 12 miRNA-mRNA predictive tools were intersected with The Cancer Genome Atlas (TCGA)-based differentially expressed genes. In addition, Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to determine the possible mechanism of miR-198-5p in LUAD. The Search Tool for the Retrieval of Interacting Genes/Proteins database was employed to construct a protein-protein interaction network among the potential target genes of miR-198-5p. The results showed that miR-198-5p expression was lower in LUAD tissues than in adjacent non-cancerous lung tissues (4.469±2.495 vs. 5.301±2.502; P=0.015). Meta-analyses, including the data from the present study and online microarray data, also verified the downregulation of miR-198-5p in 584 cases of LUAD. The expression of miR-198-5p was associated with the age, blood vessel invasion, Tumor-Node-Metastasis stage, and lymph node metastasis of patients with LUAD and served as an independent prognostic factor for survival. The hub genes of miR-198-5p were upregulated in LUAD, according to TCGA and The Human Protein Atlas. For the KEGG pathway analysis, the most enriched KEGG pathway was the p53 signaling pathway (P=1.42×10-6). These findings indicated that the downregulation of miR-198-5p may play a pivotal role in the development of LUAD by targeting various signaling pathways.

Expression levels and co­targets of miRNA­126­3p and miRNA­126­5p in lung adenocarcinoma tissues: Αn exploration with RT­qPCR, microarray and bioinformatic analyses.

Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer. Previous studies have found that many microRNAs (miRNAs), including miRNA­126­3p, may play a critical role in the development of LUAD. However, no study of LUAD has researched the synergistic effects and co­targets of both miRNA­126­3p and miRNA­126­5p. The present study used real­time quantitative polymerase chain reaction (RT­qPCR) to explore the expression values of miRNA­126­3p and miRNA­126­5p in 101 LUAD and 101 normal lung tissues. Ten relevant microarray datasets were screened to further validate the expression levels of miRNA­126­3p and ­5p in LUAD. Twelve prediction tools were employed to obtain potential targets of miRNA­126­3p and miRNA­126­5p. The results showed that both miRNA­126­3p and ­5p were expressed significantly lower in LUAD. A significant positive correlation was also present between miRNA­126­3p and ­5p expression in LUAD. In addition, lower expression of miRNA­126­3p and ­5p was indicative of vascular invasion, lymph node metastasis (LNM), and a later tumor/node/metastasis (TNM) stage of LUAD. The authors obtained 167 targets of miRNA­126­3p and 212 targets of miRNA­126­5p; 44 targets were co­targets of both. Eight co­target genes (IGF2BP1, TRPM8, DUSP4, SOX11, PLOD2, LIN28A, LIN28B and SLC7A11) were initially identified as key genes in LUAD. The results of the present study indicated that the co­regulation of miRNA­126­3p and miRNA­126­5p plays a key role in the development of LUAD, which also suggests a fail­proof mode between miRNA­3p and miRNA­126­5p.

Clinical Value and Prospective Pathway Signaling of MicroRNA-375 in Lung Adenocarcinoma: A Study Based on the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Bioinformatics Analysis.

BACKGROUND Lung adenocarcinoma (LUAD) is the most frequent lung cancer. MicroRNAs (miRNAs) are believed to have fundamental roles in tumorigenesis of LUAD. Although miRNAs are broadly recognized in LUAD, the role of microRNA-375 in LUAD is still not fully elucidated. MATERIAL AND METHODS We evaluated the significance of miR-375 expression in LUAD by using analysis of a public dataset from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database and a literature review. Furthermore, we investigated the biological function of miR-375 by gene ontology enrichment and target prediction analysis. RESULTS MiR-375 expression was significantly higher in LUAD by TCGA data compared to normal lung tissue (p<0.0001). In addition, a common pattern of upregulation for miR-375 in LUAD was found in our review of the literature. A total of 682 genes, both LUAD-related and miR-375-related, were obtained from the analytical integration. Critical pathways were unveiled in the network analysis of the overlaps, such as pentose and glucuronate interconversions, ascorbate and aldarate metabolism, and starch and sucrose metabolism. Furthermore, we identified covert miR-375 associated genes that might participate in LUAD by network analysis, such as FGF2 (fibroblast growth factor 2), PAX6 (paired box 6), and RHOJ. The expression of these three genes were all downregulated in LUAD. Finally, FGF2 was revealed to be negatively correlated with miR-375 in LUAD (r=-0.1821, p=0.0001). CONCLUSIONS Overall, our study provides evidence that miR-375 is essential for the progression of LUAD.

Implication of downregulation and prospective pathway signaling of microRNA-375 in lung squamous cell carcinoma.

BACKGROUND: Lung cancer is one of the most typical cancers in the world. Altered expression profiles of microRNA-375(miR-375) are linked to many diseases including lung cancer. However, the relationship between miR-375 and lung squamous cell carcinoma (LUSC) is controversial. METHODS: We first evaluated the 23 LUSCs and the paired normal lung tissues by qRT-PCR. Then we analyzed the LUSC samples with miR-375 expression based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Furthermore, bioinformatics analysis was performed to explore the biological role of miR-375 in LUSC. RESULTS: The expression of miR-375 was remarkably reduced in LUSC tissues compared with that in paired lung tissues by qRT-PCR (P=0.003). Additionally, the TCGA dataset suggested that miR-375 was significantly downregulated in 478 LUSC tissues compared with 45 normal lung tissues (P<0.0001), as well as the result derived from GEO datasets (the pooled SMD=-1.01; 95%CIs-1.66 to -0.33, P=0.004). Furthermore, a total of 1348 miR-375-related differently expressed genes were identified by the analytical integration, which were involved in critical pathways of LUSC like neuron differentiation, plasma membrane part and sequence-specific DNA binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway examination also unveiled the involvement of target genes in morphine addiction and drug metabolism- other enzymes and neuroactive ligand-receptor interaction. Finally, the expression of WNT5A was inversely correlated with miR-375 expression according to TCGA dataset (r=-0.2342, P<0.0001). CONCLUSIONS: miR-375 exerts a strong tumor-suppressive effect in LUSC and provided novel insight into the biological function in tumorigenesis and progression of LUSC.

Upregulation and clinicopathological significance of long non-coding NEAT1 RNA in NSCLC tissues.

BACKGROUND: Recent reports have shown that nuclear enriched abundant transcript 1 (NEAT1), a long non- coding RNA (lncRNA), contributes to the precise control of gene expression and is related to several human malignancies. However, limited data are available on the expression and function of NEAT1 in lung cancer. The major objective of the current study was to profile the expression and clinicopathological significance of NEAT1 in non-small cell lung cancers (NSCLCs). MATERIALS AND METHODS: NEAT1 expression in 125 NSCLC cases and paired adjacent non-cancer tissues was assessed by real-time quantitative reverse transcription-PCR (qRT-PCR). Relationships between NEAT1 and clinicopathological factors were also investigated. RESULTS: The relative level of NEAT1 was 6.98±3.74 in NSCLC tissues, significantly elevated as compared to that of the adjacent non-cancer lung tissues (4.83±2.98, p<0.001). The area under curve (AUC) of high expression of NEAT1 to diagnose NSCLC was 0.684 (95% CI: 0.619~0.750, p<0.001). NEAT1 expression was positively correlated with patient age (r=-2.007, p=0.047), lymphatic metastasis (r=-2.731, p=0.007), vascular invasion (r=-3.617, p=0.001) and clinical TNM stage (r=-4.134, p<0.001). CONCLUSIONS: This study indicates that NEAT1 might be associated with oncogenesis and progression in NSCLC, and suggests application in molecular targeted therapy.