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Cross-disease analysis identified novel common genes for both lung adenocarcinoma and lung squamous cell carcinoma.

ABSTRACT: Lung squamous cell carcinoma (LSCC) exhibits a number of similarities with lung adenocarcinoma (LA) in terms of copy number alterations. However, compared with LA, the range of genetic alterations in LSCC is less understood. In the present study, a large-scale literature-based search of LA-associated genes and LSCC-associated genes was performed to identify the genetic basis in common with these two diseases. For each of the LA-associated genes, a mega-analysis was performed to test its expression variations in LSCC using 11 RNA expression datasets, with significant genes identified using statistical analysis. Subsequently, a functional pathway analysis was performed to identify a possible association between any of the significant genes identified from the mega-analysis and LSCC, followed by a co-expression analysis. A multiple linear regression (MLR) model was employed to investigate the possible influence of sample size, country of origin and study date on gene expression in patients with LSCC. Disease-gene association data analysis identified 1,178 genes involved in LA, 334 in LSCC, with a significant overlap of 187 genes (P<1.02×-161). Mega-analysis revealed that three LA-associated genes, such as solute carrier family 2 member 1 (SLC2A1), endothelial PAS domain protein 1 (EPAS1) and cyclin-dependent kinase 4 (CDK4), were significantly associated with LSCC (P<1.60×10-8), with multiple potential pathways identified by functional pathway analysis, which were further validated by co-expression analysis. The present MLR analysis suggested that the country of origin was a significant factor for the levels of expression of all three genes in patients with LSCC (P<4.0×10-3). Collectively, the present results suggested that genes associated with LA should be further investigated for their association with LSCC. In addition, SLC2A1, EPAS1 and CDK4 may be novel risk genes associated with LA and LSCC.

SUBMITTER: Zhang G

PROVIDER: S-EPMC6732964 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Cross-disease analysis identified novel common genes for both lung adenocarcinoma and lung squamous cell carcinoma.

Zhang Guanghui G Wang Weijie W Huang Weiyang W Xie Xiaoli X Liang Zhigang Z Cao Hongbao H

Oncology letters 20190729 4

Lung squamous cell carcinoma (LSCC) exhibits a number of similarities with lung adenocarcinoma (LA) in terms of copy number alterations. However, compared with LA, the range of genetic alterations in LSCC is less understood. In the present study, a large-scale literature-based search of LA-associated genes and LSCC-associated genes was performed to identify the genetic basis in common with these two diseases. For each of the LA-associated genes, a mega-analysis was performed to test its expressi ...[more]

PMID: 31516564

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Project description:BackgroundTo understand the carcinogenesis caused by accumulated genetic and epigenetic alterations and seek novel biomarkers for various cancers, studying differentially expressed genes between cancerous and normal tissues is crucial. In the study, two cDNA libraries of lung cancer were constructed and screened for identification of differentially expressed genes.MethodsTwo cDNA libraries of differentially expressed genes were constructed using lung adenocarcinoma tissue and adjacent nonmalignant lung tissue by suppression subtractive hybridization. The data of the cDNA libraries were then analyzed and compared using bioinformatics analysis. Levels of mRNA and protein were measured by quantitative real-time polymerase chain reaction (q-RT-PCR) and western blot respectively, as well as expression and localization of proteins were determined by immunostaining. Gene functions were investigated using proliferation and migration assays after gene silencing and gene over-expression.ResultsTwo libraries of differentially expressed genes were obtained. The forward-subtracted library (FSL) and the reverse-subtracted library (RSL) contained 177 and 59 genes, respectively. Bioinformatic analysis demonstrated that these genes were involved in a wide range of cellular functions. The vast majority of these genes were newly identified to be abnormally expressed in lung cancer. In the first stage of the screening for 16 genes, we compared lung cancer tissues with their adjacent non-malignant tissues at the mRNA level, and found six genes (ERGIC3, DDR1, HSP90B1, SDC1, RPSA, and LPCAT1) from the FSL were significantly up-regulated while two genes (GPX3 and TIMP3) from the RSL were significantly down-regulated (P < 0.05). The ERGIC3 protein was also over-expressed in lung cancer tissues and cultured cells, and expression of ERGIC3 was correlated with the differentiated degree and histological type of lung cancer. The up-regulation of ERGIC3 could promote cellular migration and proliferation in vitro.ConclusionsThe two libraries of differentially expressed genes may provide the basis for new insights or clues for finding novel lung cancer-related genes; several genes were newly found in lung cancer with ERGIC3 seeming a novel lung cancer-related gene. ERGIC3 may play an active role in the development and progression of lung cancer.

Project description:The human microbiome is a vast collection of microbial species that exist throughout the human body and regulate various bodily functions and phenomena. Of the microbial species that exist in the human microbiome, those within the archaea domain have not been characterized to the extent of those in more common domains, despite their potential for unique metabolic interaction with host cells. Research has correlated tumoral presence of bacterial microbial species to the development and progression of lung cancer; however, the impacts and influences of archaea in the microbiome remain heavily unexplored. Within the United States lung cancer remains highly fatal, responsible for over 100,000 deaths every year with a 5-year survival rate of roughly 22.9%. This project attempts to investigate specific archaeal species' correlation to lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) incidence, patient staging, death rates across individuals of varying ages, races, genders, and smoking-statuses, and potential molecular targets associated with archaea microbiome. Archaeal species abundance was assessed across lung tissue samples of 527 LUAD patients, 479 LUSC patients, and 99 healthy individuals. Nine archaeal species were found to be of significantly altered abundance in cancerous samples as compared to normal counterparts, 6 of which are common to both LUAD and LUSC subgroups. Several of these species are of the taxonomic class Thermoprotei or the phylum Euryarchaeota, both known to contain metabolic processes distinct from most bacterial species. Host-microbe metabolic interactions may be responsible for the observed correlation of these species' abundance with cancer incidence. Significant microbes were correlated to patient gene expression to reveal genes of altered abundance with respect to high and low archaeal presence. With these genes, cellular oncogenic signaling pathways were analyzed for enrichment across cancer and normal samples. In comparing gene expression between LUAD and adjacent normal samples, 2 gene sets were found to be significantly enriched in cancers. In LUSC comparison, 6 sets were significantly enriched in cancer, and 34 were enriched in normals. Microbial counts across healthy and cancerous patients were then used to develop a machine-learning based predictive algorithm, capable of distinguishing lung cancer patients from healthy normal with 99% accuracy.

Project description:ObjectiveTo analyze the differentially expressed genes (DEGs) between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) with bioinformatics analysis and search for potential biomarkers for clinical diagnosis of nonsmall cell lung cancer (NSCLC).MethodsThe gene expression profiling datasets of LUAD and LUSC were acquired. The transcriptome differences between LUAD and LUSC were identified using R language processing and t-test analysis. The differential expressions of the genes were shown by Venn diagram. The DEGs identified by GEO2R were analyzed with DAVID and Ingenuity Pathway Analysis (IPA) to identify the signaling pathways and biomarkers that could be used for differential diagnosis of LUAD and LUSC. The TCGA data and the biomarker expression data from clinical lung cancer samples were used to verify the differential expressions of the Osteoarthritis pathway and LXR/RXR between LUAD and LUSC. We further examined the differential expressions of miR-181 and its two target genes, WNT5A and MBD2, in 23 clinical specimens of lung squamous cell carcinoma and the paired adjacent tissues.ResultsGEO data analysis identified 851 DEGs (including 276 up-regulated and 575 down-regulated genes) in LUAD and 885 DEGs (including 406 up-regulated and 479 down-regulated genes) in LUSC. DAVID and IPA analysis revealed that leukocyte migration and inflammatory responses were more abundant in LUAD than in LUSC. Osteoarthritis pathway was inhibited in LUAD and activated in LUSC. IPA analysis showed that transcription factors (GATA4, RELA, YBX1, TP63 and MBD2), cytokines (WNT5A and IL1A) and microRNAs (miR-34a, miR-181b and miR-15a) differed significantly between LUAD and LUSC. miR-34a with IL-1A, miR-15a with YBX1, and miR-181b with WNT5A and MBD2 could serve as the paired microRNA and mRNA targets for differential diagnosis of NSCLC subtypes. Analysis of the clinical samples showed an increased expression of miR-181b-5p and the down-regulation of WNT5A, which could be used as molecular markers for the diagnosis of LUSC.ConclusionsThrough transcriptome analysis, we identified candidate genes, paired microRNAs and pathways for differentiating LUAD and LUSC, and they can provide novel differential diagnosis and therapeutic strategies for LUAD and LUSC.

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Cross-disease analysis identified novel common genes for both lung adenocarcinoma and lung squamous cell carcinoma.

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Cross-disease analysis identified novel common genes for both lung adenocarcinoma and lung squamous cell carcinoma.

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