Genome-Wide Analysis of DNA Methylation and the Gene Expression Change in Lung Cancer

Kwon, Yong Hwan; Lee, Seog Joo; Koh, Jae Soo; Kim, Sung-Han; Lee, Hae Won; Kang, Moon Gi; Bae, Jae Bum; Kim, Young-Joon; Park, Jong Ho

doi:10.1097/jto.0b013e3182307f62

Cited by 82 publications

(59 citation statements)

References 48 publications

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“…Recently, aberrant LMO3 expression in other various types of malignant cells has been reported 27, 28, 29. Our samples examined also did not include any neuronal tissue, so that the further investigation of the LMO3 expression is valuable for understanding its exact role in both normal and tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B‐cell lymphoma cells and their association with clinical features

et al. 2016

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Diffuse large B‐cell lymphoma (DLBCL) is clinicopathologically and genetically heterogeneous with variable clinical outcomes. We previously identified signature genes overexpressed in CD5‐positive (CD5+) DLBCL, which is a poor prognostic subgroup of DLBCL. To elucidate the clinical significance of the protein expression of the signature genes overexpressed in CD5+ DLBCL with regard to all DLBCL, not otherwise specified (NOS), 10 genes (SH3BP5,LMO3,SNAP25,SYT5,SV2C,CABP1,FGF1,FGFR2,NEUROD1, and SYN2) were selected and examined immunohistochemically with samples from 28 patients with DLBCL, NOS. Only three protein expressions, SH3BP5, LMO3, and SNAP25, were detected in DLBCL cells and then analyzed further with samples from 187 patients with DLBCL, NOS. The SH3BP5, LMO3, and SNAP25 proteins were expressed in 60% (103/173), 34% (59/175), and 46% (77/168) of DLBCL patients, respectively. These protein expressions were associated with CD5 expression, and only SH3BP5 was frequently expressed in activated B‐cell‐like DLBCL (P = 0.046). Compared to the SH3BP5‐negative group, the SH3BP5+ group was correlated with elderly onset (>60 years, P = 0.0096) and advanced‐stage disease (stage III/IV, P = 0.037). The LMO3+ group showed a worse performance status (>1, P = 0.0004). The SH3BP5+ group and the LMO3+ group had significantly worse overall survival than the negative groups (P = 0.030, 0.034; respectively) for the entire group. In a subgroup analysis of patients treated with rituximab‐containing chemotherapy, there was no significant difference between groups. To the best of our knowledge, this is the first report showing the protein expressions of SH3BP5, LMO3, and SNAP25 in DLBCL cells and their clinical significance in patients with DLBCL. The SH3BP5 and LMO3 protein expressions are associated with the baseline clinical characteristics of DLBCL.

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Section: Discussionmentioning

confidence: 99%

Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B‐cell lymphoma cells and their association with clinical features

et al. 2016

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“…We analyzed the Gene Expression Omnibus Profiles of CYTL1 and observed that CYTL1 expression was low in human prostate cancer (GDS1438/219837_s_at/CYTL1), N-methyl-N-nitrosourea-induced rat breast cancer (GDS1363/ 1375001_at/Cytl1), and SP-C/c-raf transgenic mouse lung cancer (GDS3826/1456793_at/Cytl1). Furthermore, CYTL1 was recently reported to be hypermethylated in lung squamous cell carcinoma, and there were typical CpG islands in the CYTL1 promoter (51). Thus, CYTL1 might exert tumor-suppressing effects.…”

Section: Discussionmentioning

confidence: 99%

Cytokine-like 1 Chemoattracts Monocytes/Macrophages via CCR2

Wang

et al. 2016

The Journal of Immunology

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Cytokine-like 1 (CYTL1) is a novel potential cytokine that was first identified in CD34+ cells derived from bone marrow and cord blood, and it was also found using our immunogenomics strategy. The immunobiological functions of CYTL1 remain largely unknown, and its potential receptor(s) has not been identified. A previous proposed hypothesis suggested that CYTL1 had structural similarities with CCL2 and that CCR2 was a potential receptor of CYTL1. In this study, we verify that CYTL1 possesses chemotactic activity and demonstrate that its functional receptor is CCR2B using a series of experiments performed in HEK293 cells expressing CCR2B or CCR2B-EGFP, including chemotaxis, receptor internalization, and radioactive binding assays. CYTL1 chemoattracts human monocytes but not PBLs, and its chemotactic activity toward monocytes is dependent on the CCR2B-ERK pathway. Furthermore, both human and mouse recombinant CYTL1 protein have chemotactic effects on macrophages from wild-type mice but not from Ccr2−/− mice. Furthermore, the chemotactic activity of CYTL1 is sensitive to pertussis toxin. All of the above data confirm that CCR2B is a functional receptor of CYTL1.

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“…ADAMTS12 has been shown to be associated with outcome in colorectal cancer [18]; however, to our knowledge this is the first time that ADAMTS12 has been linked to RCC. SLIT2 and LMO3 have been reported to be hypermethylated in pulmonary tumors (another smoking-related cancer) relative to patient-matched normal pulmonary tissue [19] and LMO3 has been shown to have oncogenic potential in neuroblastoma [20]. The SLIT/ROBO pathway is reported to be a therapeutic target for cancer [21].…”

Section: Discussionmentioning

confidence: 99%

Differential gene expression profiling of matched primary renal cell carcinoma and metastases reveals upregulation of extracellular matrix genes

Serie²,

Parasramka³

et al. 2017

Annals of Oncology

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Background: The majority of renal cell carcinoma (RCC) studies analyze primary tumors, and the corresponding results are extrapolated to metastatic RCC tumors. However, it is unknown if gene expression profiles from primary RCC tumors differs from patient-matched metastatic tumors. Thus, we sought to identify differentially expressed genes between patient-matched primary and metastatic RCC tumors in order to understand the molecular mechanisms underlying the development of RCC metastases. Patients and methods:We compared gene expression profiles between patient-matched primary and metastatic RCC tumors using a two-stage design. First, we used Affymetrix microarrays on 15 pairs of primary RCC [14 clear cell RCC (ccRCC), 1 papillary] tumors and patient-matched pulmonary metastases. Second, we used a custom NanoString panel to validate seven candidate genes in an independent cohort of 114 ccRCC patients. Differential gene expression was evaluated using a mixed effect linear model; a random effect denoting patient was included to account for the paired data. Third, The Cancer Genome Atlas (TCGA) data were used to evaluate associations with metastasis-free and overall survival in primary ccRCC tumors.Results: We identified and validated up regulation of seven genes functionally involved in the formation of the extracellular matrix (ECM): DCN, SLIT2, LUM, LAMA2, ADAMTS12, CEACAM6 and LMO3. In primary ccRCC, CEACAM6 and LUM were significantly associated with metastasis-free and overall survival (P < 0.01). Conclusions:We evaluated gene expression profiles using the largest set to date, to our knowledge, of patient-matched primary and metastatic ccRCC tumors and identified up regulation of ECM genes in metastases. Our study implicates up regulation of ECM genes as a critical molecular event leading to visceral, bone and soft tissue metastases in ccRCC.

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Genome-Wide Analysis of DNA Methylation and the Gene Expression Change in Lung Cancer

Abstract: In conclusion, by combining the whole-genome DNA methylation pattern and the gene expression profile, we identified the six genes (CCDC37, CYTL1, CDO1, SLIT2, LMO3, and SERPINB5) that are regulated by DNA methylation, and we suggest their value as target molecules for further study of SCC.

Cited by 82 publications

References 48 publications

Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B‐cell lymphoma cells and their association with clinical features

Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B‐cell lymphoma cells and their association with clinical features

Cytokine-like 1 Chemoattracts Monocytes/Macrophages via CCR2

Differential gene expression profiling of matched primary renal cell carcinoma and metastases reveals upregulation of extracellular matrix genes

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