Integrated analyses of copy number variations and gene differential expression in lung squamous-cell carcinoma

Zhao, Yang; Zhuan, Bing; Yan, Yan; Jiang, Simin; Wang, Tao

doi:10.1186/s40659-015-0038-3

Cited by 18 publications

(16 citation statements)

References 35 publications

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“…Methylation of high-density CpG regions known as CpG islands (CGIs) has been widely described as a mechanism associated with gene expression regulation (21), whereas no methylation change of NUSAP1 (0/34, 0%) was identified in the present study. In addition, in a previous study using both transcriptional profile data and CNA, they identified that genes with differential expression may be caused by CNAs (22). To our surprise, CNAs of NUSAP1 existed in all of the 61 paired RCCs, which suggest that CNAs could be the primary cause for the overexpression of NUSAP1 in RCC.…”

Section: Discussionmentioning

confidence: 61%

Downregulation of nucleolar and spindle-associated protein 1 expression suppresses cell migration, proliferation and invasion in renal cell carcinoma

et al. 2016

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Nucleolar and spindle-associated protein 1 (NUSAP1) is a microtubule-binding protein that plays an essential role in mitosis and cancer. Previous studies have demonstrated that NUSAP1 expression is relatively elevated in several malignancies. However, the biological roles of NUSAP1 in renal cell carcinoma (RCC) remain unknown. In the present study, we firstly performed reverse transcription‑polymerase chain reaction (RT-PCR) and western blot analysis to reveal that the expression of NUSAP1 was relatively elevated in clear cell RCC (ccRCC) tissue specimens and RCC cell lines. Immunohistochemical analysis showed that upregulation of NUSAP1 was significantly correlated with Fuhrman grade (P<0.001), tumor size (P=0.016), clinical stage (P<0.001) and distant metastasis (P=0.023). Additionally, high expression of NUSAP1 was closely associated with a shorter overall survival time of the ccRCC patients (P=0.006). Furthermore, we investigated the biological behaviors of RCC cells in vitro, and we identified that NUSAP1 depletion inhibited RCC cell migration, proliferation and invasion, and apoptosis was induced and the cell cycle was arrested. On the basis of our studies, NUSAP1 was identified as a potential prognostic indicator and a novel therapeutic target for RCC patients.

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Section: Discussionmentioning

confidence: 61%

Downregulation of nucleolar and spindle-associated protein 1 expression suppresses cell migration, proliferation and invasion in renal cell carcinoma

et al. 2016

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“…The expression levels of 13 previously reported immune metagenes were calculated as the mean of the log2-transformed expression of the member genes (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). These metagenes correspond to various immune cell types and reflect various immune functions ( Supplementary Table S2).…”

Section: Analysis Planmentioning

confidence: 99%

“…In a pooled analysis of solid tumors in The Cancer Genome Atlas (TCGA) database, the total number of somatic mutations and the number of new antigen epitopes (i.e., neoantigen load) correlated with immune infiltration (9)(10)(11). In hepatocellular, squamous cell lung cancer, and colorectal carcinomas greater number of copy number alterations were associated with higher immunogenicity (12)(13)(14). On the basis of these observations one can hypothesize that the more genomic alterations a cancer has, the greater the immune infiltration is, due to more immunogenic neoantigens in these cancers.…”

Section: Introductionmentioning

confidence: 99%

Immune Gene Expression Is Associated with Genomic Aberrations in Breast Cancer

et al. 2017

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The presence of tumor-infiltrating lymphocytes (TIL) is a favorable prognostic factor in breast cancer, but what drives immune infiltration remains unknown. Here we examine if clonal heterogeneity, total mutation load, neoantigen load, copy number variations (CNV), gene- or pathway-level somatic mutations, or germline polymorphisms (SNP) are associated with immune metagene expression in breast cancer subtypes. Thirteen published immune metagenes correlated separately with genomic metrics in the three major breast cancer subtypes. We analyzed RNA-Seq, DNA copy number, mutation and germline SNP data of 627 ER, 207 HER2, and 191 triple-negative (TNBC) cancers from The Cancer Genome Atlas. -values were adjusted for multiple comparisons, and permutation testing was used to assess false discovery rates. Increased immune metagene expression associated significantly with lower clonal heterogeneity estimated by MATH score in all subtypes and with a trend for lower overall mutation, neoantigen, and CNV loads in TNBC and HER2 cancers. In ER cancers, mutation load, neoantigen load, and CNV load weakly but positively associated with immune infiltration, which reached significance for overall mutation load only. No highly recurrent single gene or pathway level mutations associated with immune infiltration. High immune gene expression and lower clonal heterogeneity in TNBC and HER2 cancers suggest an immune pruning effect and equilibrium between immune surveillance and clonal expansion. Thus, immune checkpoint inhibitors may tip the balance in favor of immune surveillance in these cancers. .

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“…A prostate cancer study showed that CNA burden can be regarded as a prognostic biomarker associated with cancer biochemical recurrence and metastasis ( Hieronymus et al, 2014 ). Also, a recent lung cancer study revealed that squamous cell carcinoma lung cancer patients have an increased copy number burden in most of the individual chromosomes, particularly in the length of 50 kb ( Yang et al, 2015 ). In consistence, investigations about the role of CNAs in patients with malignant melanomas presented an association between CNA and poor outcomes ( Hirsch et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Association Analysis of Somatic Copy Number Alteration Burden With Breast Cancer Survival

et al. 2018

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The increasing prevalence of diagnosed breast cancer cases emphasizes the urgent demand for developing new prognostic breast cancer biomarkers. Copy number alteration (CNA) burden measured as the percentage of the genome affected by CNAs has emerged as a potential candidate to this aim. Using somatic CNA data obtained from METABRIC (Molecular Taxonomy of Breast Cancer International Consortium), we implemented Kaplan-Meier estimators and Cox proportional hazards models to examine the association of CNA burden with patient’s overall survival (OS) and disease specific survival (DSS). We also evaluated the association by considering patients’ age and tumor subtypes using stratified Cox models. We delineated the distribution of CNA burden in sample genomes and highlighted chromosomes 1, 8, and 16 as the carriers of the highest CNA burden. We identified a strong association between CNA burden and age as well as CNA burden and breast cancer PAM50 subtypes. We found that controlling the effects of both age (bound by 45-year) and PAM50 subtypes on patient survival using stratified Cox models, would still result in significant association between CNA burden and patients overall survival in both Discovery and Validation data. The same trend was observed in disease specific survival when only PAM50 subtypes were controlled in the stratified Cox models. Our analysis showed that there is a significant association between CNA burden and breast cancer survival. This result is also validated by using TCGA (The Cancer Genome Atlas) data. CNA burden of breast cancer patients has a considerable potential to be used as a novel prognostic biomarker.

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Integrated analyses of copy number variations and gene differential expression in lung squamous-cell carcinoma

Cited by 18 publications

References 35 publications

Downregulation of nucleolar and spindle-associated protein 1 expression suppresses cell migration, proliferation and invasion in renal cell carcinoma

Downregulation of nucleolar and spindle-associated protein 1 expression suppresses cell migration, proliferation and invasion in renal cell carcinoma

Immune Gene Expression Is Associated with Genomic Aberrations in Breast Cancer

Association Analysis of Somatic Copy Number Alteration Burden With Breast Cancer Survival

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