Differences in gene expression levels between early and later stages of human lung development are opposite to those between normal lung tissue and non-small lung cell carcinoma

11066 Background: Oncogenic driving alterations define types of lung adenocarcinoma with different prognosis and sensitivity to targeted agents. MicroRNAs (miRNAs) are a new class of non-coding RNAs involved in gene expression regulation. How miRNAs are dysregulated in lung cancer with ALK translocation, EGFR or KRAS mutation is unknown. In this study we aimed to identify miRNA signatures according to the presence of specific driver and to correlate miRNAs deregulation with patient outcome. Methods: The study was conducted in a cohort of 70 lung cancer patients (pts) including 18 ALK+ tumors, 11 ALK-/EGFR mutation+, 15 ALK-/KRAS mutation+, 26 ALK-/EGFR and KRAS wild-type and defined as triple negative. Matched normal lung tissue from 18 cases representative of the entire cohort were also included onto the analysis. RNA was isolated from formalin-fixed paraffin-embedded tissue (FFPE), using the Recover ALL kit (Ambion). NanoString nCounter system platform was used to generate the miRNA profile. We used Limma to test for differential expression analysis of data. The miR-515 family expression between tissues was validated by RT-qPCRs, analyzed using the parametric t-test (unpaired, 2-tailed for validation). Results: miRNA expression profile clusters distinctly ALK+ pts from ALK- and normal lung tissue. Within the ALK- group we found specific miRNAs subsets able to sub-stratify KRAS versus EGFR careers clustering sharply triple negative versus EGFR mutation+ and triple negative versus KRAS mutation+. miRNAs belonging to the miR-515 family seems to be the most deregulated in the ALK+ versus ALK-. Although their expression is stably high in normal tissues and ALK+ class, they are highly downregulated in KRAS mutated versus EGFR mutated and versus triple negative (p-value <0.001 for all comparisons). Conclusions: miRNAs profile significantly differs in pts with ALK translocation, EGFR mutations and KRAS mutations. Analysis of miR-515 family members is ongoing in order to correlate their expression levels with pts’ outcome. In vitro modulation of miR-515 family expression levels, together with drugs treatment are ongoing in order to find possible chemo-resistance/chemo-sensitivity miRNA dependent, in ALK+ and ALK- model.

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Prediction of the gene expression in normal lung tissue by the gene expression in blood

BMC Medical Genomics ◽

10.1186/s12920-015-0152-7 ◽

2015 ◽

Vol 8 (1) ◽

Cited By ~ 3

Author(s):

Justin W. Halloran ◽

Dakai Zhu ◽

David C. Qian ◽

Jinyoung Byun ◽

Olga Y. Gorlova ◽

...

Keyword(s):

Gene Expression ◽

Lung Tissue ◽

Normal Lung Tissue ◽

Normal Lung

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Impact of gene expression of orotate phosphoribosyl transferase for complete response to chemoradiotherapy in patients with squamous cell carcinoma of the esophagus

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.4566 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 4566-4566

Author(s):

T. Kajiwara ◽

T. Nishina ◽

I. Hyodo ◽

T. Moriwaki ◽

S. Endo ◽

...

Keyword(s):

Gene Expression ◽

Squamous Cell Carcinoma ◽

Growth Factor ◽

Cell Carcinoma ◽

Squamous Cell ◽

Predictive Factor ◽

Complete Response ◽

Carcinoma Of The Esophagus ◽

Expression Levels ◽

Gene Expression Levels

4566 Background: Chemoradiotherapy (CRT) is a potential alternative to surgery in patients with squamous cell carcinoma of the esophagus. Complete response (CR) to CRT is essential for a good prognosis and there is a need for a predictive method of CR in CRT. Methods: The pretreatment formalin-fixed, paraffin-embedded endoscopic tumor biopsy material was obtained from 41 patients treated with a definitive concurrent CRT (5-FU/CDDP and 60 Gy) for esophageal cancer (cStage II or III). cDNA was derived from tumor cells of biopsy specimens by the laser capture microdissection and analyzed to determine mRNA expression relative to an internal reference gene (β-actin) using fluorescence-based, real-time reverse transcription PCR. Gene expression levels of thymidylate synthase, thymidine phosphorylase, dihydropyrimidine dehydrogenase, orotate phosphoribosyl transferase (OPRT), metylenetetrahydrofolate reductase, dihydrofolate reductase (DHFR), excision repair cross-complementing gene 1, vascular endothelial growth factor, epidermal growth factor receptor and matrix metalloproteinase 9 (MMP-9) were measured. Results: Median gene expression levels of OPRT and DHFR were significantly higher in CR patients (p=0.0206 and 0.0191, respectively). MMP-9 was significantly lower in CR patients (p=0.0436). When the median values of the gene expression levels were selected as the cutoff values, CR rate was significantly higher in the high OPRT group and high DHFR group (p=0.0104 and 0.0104, respectively). However, there was no statistical difference in CR rate between the low MMP-9 group and the high MMP-9 group. Multivariate analysis, including clinical stage and biomarkers, revealed that high OPRT gene expression was an independent predictive factor of CR (p=0.0329, relative risk=6.65, 95% confidence interval, 1.17–37.89%). Conclusions: The measurement of OPRT gene expression in tumor biopsies may be a predictive factor of CR to CRT in patients with squamous cell carcinoma of the esophagus. No significant financial relationships to disclose.

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Diagnostic value of integrin α3, β4, and β5 gene expression levels for the clinical outcome of tongue squamous cell carcinoma

Cancer ◽

10.1002/cncr.23295 ◽

2008 ◽

Vol 112 (6) ◽

pp. 1272-1281 ◽

Cited By ~ 39

Author(s):

Akira Kurokawa ◽

Masaki Nagata ◽

Nobutaka Kitamura ◽

Arhab A. Noman ◽

Makoto Ohnishi ◽

...

Keyword(s):

Gene Expression ◽

Squamous Cell Carcinoma ◽

Clinical Outcome ◽

Cell Carcinoma ◽

Squamous Cell ◽

Diagnostic Value ◽

Tongue Squamous Cell Carcinoma ◽

Expression Levels ◽

Gene Expression Levels

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PD-1H Expression Associated With CD68 Macrophage Marker Confers an Immune-Activated Microenvironment and Favorable Overall Survival in Human Esophageal Squamous Cell Carcinoma

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.777370 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yuangui Chen ◽

Rui Feng ◽

Bailin He ◽

Jun Wang ◽

Na Xian ◽

...

Keyword(s):

Gene Expression ◽

Overall Survival ◽

Squamous Cell Carcinoma ◽

T Cells ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Expression Levels ◽

Tumor Tissues ◽

Gene Expression Levels

Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal carcinoma (EC) in China. Although the PD-1 inhibitor pembrolizumab has been approved to treat patients with EC, its therapeutic efficacy is limited. Thus, additional immunotherapeutic targets for EC treatment are needed. Programmed Death-1 Homolog (PD-1H) is a negative checkpoint regulator that inhibits antitumor immune responses. Here, PD-1H expression in 114 patients with ESCC was evaluated by immunohistochemistry. Next, 12 randomly selected tumor tissue sections were used to assess the colocalization of PD-1H protein and multiple immune markers by multiplex immunohistochemistry. Our results demonstrated that PD-1H was expressed at high frequency in ESCC tumor tissues (85.1%). PD-1H protein was predominantly expressed in CD68+ tumor-associated macrophages and expressed at low levels in CD4+ T cells and CD8+ T cells in ESCC tumor tissues. Furthermore, based on ESCC data in The Cancer Genome Atlas (TCGA), the gene expression levels of PD-1H were positively associated with the infiltration levels of immune-activated cells especially CD8+ cytotoxic T cells. In contrast, the gene expression levels of PD-1H were negatively correlated with myeloid-derived suppressor cells (MDSCs). Importantly, PD-1H expression in tumor sites was significantly correlated with favorable overall survival in patients with ESCC. Collectively, our findings first provided direct information on the PD-1H expression pattern and distribution in ESCC, and positive correlation of PD-1H expression with overall survival suggested PD-1H expression levels could be a significant prognostic indicator for patients with ESCC. Future studies need to explore the immunoregulatory of PD-1H in the tumor microenvironment of ESCC.

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Localisation of transforming growth factor β1 and β3 mRNA transcripts in normal and fibrotic human lung

Thorax ◽

10.1136/thx.56.7.549 ◽

2001 ◽

Vol 56 (7) ◽

pp. 549-556

Author(s):

R K Coker ◽

G J Laurent ◽

P K Jeffery ◽

R M du Bois ◽

C M Black ◽

...

Keyword(s):

Gene Expression ◽

Growth Factor ◽

Lung Tissue ◽

Lung Fibrosis ◽

Transforming Growth Factor ◽

Human Lung ◽

In Situ Hybridisation ◽

Normal Lung ◽

Gene And Protein Expression ◽

Mrna Transcripts

BACKGROUNDTransforming growth factor β1 is implicated in the pathogenesis of lung fibrosis. It promotes extracellular matrix accumulation by increasing procollagen synthesis and reducing degradation. TGFβ1 gene and protein expression increase in experimental lung fibrosis, and TGFβ1 antibodies attenuate fibrosis in mice. The role of other TGFβ isoforms is unclear. This study aimed to localise TGFβ1 and TGFβ3 gene expression in fibrotic human lung and compare it with that in normal human lung.METHODSLung tissue from patients with cryptogenic fibrosing alveolitis and fibrosis associated with systemic sclerosis was examined by in situ hybridisation. Macroscopically normal lung from carcinoma resections was used as control tissue. Digoxigenin labelled riboprobes were synthesised from TGFβ isoform specific cDNA templates.RESULTSThe digoxigenin labelled riboprobes were sensitive and permitted precise cellular localisation of mRNA transcripts. TGFβ1 and TGFβ3 mRNA transcripts were widespread in normal lung and localised to alveolar macrophages and bronchiolar epithelium. TGFβ1 but not TGFβ3 mRNA was detected in mesenchymal and endothelial cells. In fibrotic lung tissue mRNA transcripts for both isoforms were also detected in metaplastic type II cells. TGFβ1 gene expression was enhanced in some patients. TGFβ3 was expressed in fibrotic lung but was not consistently altered compared with controls.CONCLUSIONTGFβ1mRNA transcripts were localised in normal and fibrotic human lung and TGFβ3 gene expression in human lung fibrosis was shown for the first time. The results suggest that TGFβ1 may play the predominant role in pathogenesis. It is suggested that TGFβ1 should be the primary target of anticytokine treatments for pulmonary fibrosis.

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Expression of CYP1A1 gene in patients with lung cancer: Evidence for cigarette smoke-induced gene expression in normal lung tissue and for altered gene regulation in primary pulmonary carcinomas

Lung Cancer ◽

10.1016/0169-5002(91)90128-s ◽

1991 ◽

Vol 7 (3) ◽

pp. 187

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Gene Regulation ◽

Cigarette Smoke ◽

Lung Tissue ◽

Normal Lung Tissue ◽

Normal Lung ◽

Cyp1a1 Gene ◽

Altered Gene

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Expression of CYP1A1 Gene in Patients With Lung Cancer: Evidence for Cigarette Smoke-Induced Gene Expression in Normal Lung Tissue and for Altered Gene Regulation in Primary Pulmonary Carcinomas

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/82.16.1333 ◽

1990 ◽

Vol 82 (16) ◽

pp. 1333-1339 ◽

Cited By ~ 207

Author(s):

T. L. McLemore ◽

S. Adelberg ◽

M. C. Liu ◽

N. A. McMahon ◽

S. J. Yu ◽

...

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Gene Regulation ◽

Cigarette Smoke ◽

Lung Tissue ◽

Normal Lung Tissue ◽

Normal Lung ◽

Cyp1a1 Gene ◽

Altered Gene

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Analysis of the Expression and Clinical Significance of VIPR1 in Lung Adenocarcinoma Based on TCGA Database

10.21203/rs.3.rs-1058170/v1 ◽

2021 ◽

Author(s):

Xiaobo Li ◽

Yunfei Wang ◽

Xiaowan Wei ◽

Guojun Zhang ◽

Huaqi Wang

Keyword(s):

Lung Adenocarcinoma ◽

Clinical Significance ◽

Lung Tissue ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Functional Enrichment ◽

Normal Lung Tissue ◽

Normal Lung ◽

Clinical Prognosis ◽

Expression Levels

Abstract Background: The expression of VIPR1 is associated with the prognosis of many malignant tumors. To analyze the expression and clinical significance of vasoactive intestinal peptide Types I (VIPR1) in lung adenocarcinoma based on The Cancer Genome Atlas (TCGA)database. Methods and results：The RNASeq data, clinical data and prognosis data of lung adenocarcinoma and normal lung tissue were downloaded from TCGA database. The expression difference of VIPR1 mRNA in lung adenocarcinoma and normal lung tissue（p<0.05）, and the correlations of the expression levels of VIPR1 in lung adenocarcinoma with clinical pathological characteristics and prognosis were analyzed. The possible regulatory signaling pathways of VIPR1 were predicted by the gene set enrichment analysis (GSEA). CIBERSORT was used to analyze the expression of immune cells in tumor tissues and normal tissues. TIMER was used to analyze the relationship between VIPR1 and immune cell expression. The expression levels of VIPR1 mRNA in lung adenocarcinoma tissues were significantly lower than that in normal lung tissues. The expression levels of VIPR1 mRNA were significantly correlated with gender, T staging，N staging and pathological grade（p<0.05）but not with age, M staging and survival status. Survival analysis showed that the survival time of patients with low expression of VIPR1 was significantly lower than that of patients with high expression. In addition, the expression level of VIPR1 in lung adenocarcinoma was negatively correlated with the infiltration level of myeloid inhibitory cells (r = -0.448, p < 0.01). Through GSEA functional enrichment analysis, it was found that VIPR1 was mainly related to cell cycle pathway, p53 signal pathway, DNA replication pathway, RNA degradation pathway and so on.Conclusions：VIPR1 gene may be a new target for the clinical prognosis and targeted therapy of lung adenocarcinoma.

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