Dataset Information

[Expression of transcription factor SOX12 in lung adenocarcinoma and its clinical significance].

ABSTRACT: OBJECTIVE:To explore the expression patterns of transcription factor SOX12 in lung adenocarcinoma and its significance in the diagnosis and prognosis of the malignancy. METHODS:Large cancer genome databases were used to analyze SOX12 expression level in lung adenocarcinoma. Immunohistochemistry (IHC) and semiquantitative PCR were used to detect the expression of SOX12 in 36 specimens of lung adenocarcinoma tissues, 15 adjacent tissues and 21 normal lung tissues. The prognostic value of SOX12 in lung adenocarcinoma and lung squamous cell carcinoma were analyzed using Kaplan-Meier Plotter database, and the relationship between SOX12 expression and the overall survival (OS) and progression free survival (PPS) of the patients were analyzed. RESULTS:Analysis of TCGA database and GEO (GSE40419) database showed that SOX12 expression levels were significantly higher in in lung adenocarcinoma than in normal lung tissues (P < 0.001). The results of IHC and semiquantitative PCR revealed that SOX12 was expressed at significantly higher levels in lung adenocarcinoma than in normal lung tissues (P < 0.001). Kaplan-Meier survival analysis showed that patients with lung adenocarcinoma positive for SOX12 had a significantly shorter OS and PPS time than those negative for SOX12 (P < 0.05), but SOX12 positivity did not significantly affect OS and PPS of patients with lung squamous cell carcinoma. CONCLUSIONS:High expression levels of SOX12 in lung adenocarcinoma are significantly associated with a poor OS of the patients, suggesting the value of SOX12 to assist in early diagnosis and prognostic evaluation of lung adenocarcinoma.

SUBMITTER: Li L

PROVIDER: S-EPMC6765647 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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[Expression of transcription factor SOX12 in lung adenocarcinoma and its clinical significance].

Li Li L Zhang Tingting T Chen Yuhua Y Song Jia J Meng Yao Y Liu Shu S Xie Jianming J

Nan fang yi ke da xue xue bao = Journal of Southern Medical University 20190201 2

<h4>Objective</h4>To explore the expression patterns of transcription factor SOX12 in lung adenocarcinoma and its significance in the diagnosis and prognosis of the malignancy.<h4>Methods</h4>Large cancer genome databases were used to analyze SOX12 expression level in lung adenocarcinoma. Immunohistochemistry (IHC) and semiquantitative PCR were used to detect the expression of SOX12 in 36 specimens of lung adenocarcinoma tissues, 15 adjacent tissues and 21 normal lung tissues. The prognostic val ...[more]

PMID: 30890507

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Project description:There are multiple transcription start sites (TSSs) in agreement with multiple transcript variants encoding different isoforms of NKX2-1/TTF-1 (thyroid transcription factor 1); however, the clinicopathological significance of each transcript isoform of NKX2-1/TTF-1 in lung adenocarcinoma (LAD) is unknown. Herein, TSS-level expression of NKX2-1/TTF-1 isoforms was evaluated in 71 LADs using bioinformatic analysis of cap analysis of gene expression (CAGE)-sequencing data, which provides genome-wide expression levels of the 5'-untranslated regions and the TSSs of different isoforms. Results of CAGE were further validated in 664 LADs using in situ hybridisation. Fourteen of 17 TSSs in NKX2-1/TTF-1 (80% of known TSSs in FANTOM5, an atlas of mammalian promoters) were identified in LADs, including TSSs 1-13 and 15; four isoforms of NKX2-1/TTF-1 transcripts (NKX2-1_001, NKX2-1_002, NKX2-1_004, and NKX2-1_005) were expressed in LADs, although NKX2-1_005 did not contain a homeodomain. Among those, six TSSs regulated NKX2-1_004 and NKX2-1_005, both of which contain exon 1. LADs with low expression of isoforms from TSS region 11 regulating exon 1 were significantly associated with poor prognosis in the CAGE data set. In the validation set, 62 tumours (9.3%) showed no expression of NKX2-1/TTF-1 exon 1; such tumours were significantly associated with older age, EGFR wild-type tumours, and poor prognosis. In contrast, 94 tumours, including 22 of 30 pulmonary invasive mucinous adenocarcinomas (IMAs) exhibited exon 1 expression without immunohistochemical TTF-1 protein expression. Furthermore, IMAs commonly exhibited higher exon 1 expression relative to that of exon 4/5, which contained a homeodomain in comparison with EGFR-mutated LADs. These transcriptome and clinicopathological results reveal that LAD use at least 80% of NKX2-1 TSSs and expression of the NKX2-1/TTF-1 transcript isoform without exon 1 (NKX2-1_004 and NKX2-1_005) defines a distinct subset of LAD characterised by aggressive behaviour in elder patients. Moreover, usage of alternative TSSs regions regulating NKX2-1_005 may occur in subsets of LADs.

Project description:ObjectiveTo explore the expression of secreted phosphoprotein 1 (SPP1) in lung adenocarcinoma (LUAD), and evaluate its relationship with clinicopathological characteristics and prognosis of LUAD, and analyze the advantages of SPP1 as a potential prognostic marker in LUAD.MethodsThe expression of SPP1 in normal lung tissue and LUAD was analyzed from the Cancer Cell Line Encyclopedia (CCLE), Gene Expression Omnibus (GEO), and Human Protein Atlas (HPA) databases. GSE68465 was used to explore the relationship between the SPP1 expression and clinicopathological characteristics and the prognosis of LUAD patients. The relationship between SPP1 and immune infiltration in LUAD was analyzed by the Tumor Immune Estimation Resource (TIMER) database. Gene enrichment analysis was performed in GSEA. The Cancer Genome Atlas (TCGA)-LUAD data was used to verify the results.ResultsIn the cell line level, non-small cell lung cancer ranked ninth among cancer cell lines based on SPP1 expression. In the messenger RNA (mRNA) and protein levels, SPP1 expression was higher in LUAD tissues than that in normal control. SPP1 expression was related to gender, N stage, histological grade, and progression or relapse. In men, SPP1 expression were higher compared to that in women. The higher the N stage, the higher the SPP1 expression level. As LUAD progresses or relapses, SPP1 expression could increase. In the pathological grade, the SPP1 expression was higher in LUAD samples with moderate differentiation. In addition, the overall 5-year survival rates of the SPP1 high and low expression groups were 50.574 and 59.181% [P = 0.008; hazard ratio (HR) = 0.7057; 95% CI, 0.5467-0.9109], indicating that SPP1 had an impact on overall survival for LUAD patients. The relationship between SPP1 expression and CD4+ T cell, macrophage, neutrophil, and dendritic cell infiltration was weak in LUAD. SPP1 could be considered as an independent prognostic marker in LUAD (P = 0.003; HR = 1.150; 95% CI, 1.048-1.261) by multivariate Cox regression analysis. The results of GSEA indicated that samples with high SPP1 expression were enriched in protein secretion, mTORC1 signaling, angiogenesis, and glycolysis pathway. The analysis results obtained by TCGA-LUAD data were basically consistent with the results obtained by GSE68465.ConclusionsSPP1 can not only affect the occurrence and development of LUAD but also may be an independent prognostic marker of LUAD. SPP1 is expected to be a new target for molecular targeted therapy.

Project description:Non-small cell lung cancer is a subtype of adenocarcinoma, which has previously shown positive responses to gefitinib. The aim of the current study was to determine a clinical profile of gefitinib-induced disease controls for patients with lung adenocarcinoma. Retrospective evaluation of the clinical characteristics of 52 lung adenocarcinoma patients, enrolled at the Zhejiang Cancer Hospital (Hangzhou, China) between October 2004 and August 2008, was undertaken. All patients received gefitinib (250 mg/day orally) until disease progression or until an unacceptable toxicity was observed. Of the 52 patients, complete response (CR) and partial response (PR) rates were 23.1% (12/52) and 57.7% (30/52), respectively. An additional 19.2% (10/52) of patients demonstrated stable disease (SD) after three months of treatment with gefitinib. Disease control was observed in the primary lesion, and tumor metastasis to the lungs, brain, adrenal glands, pleura, peritoneum, pericardium, bone and lymph nodes was identified. The one-year progression-free survival (PFS) and overall survival (OS) rates were 74.8 and 78.0%, respectively. Multivariate analysis revealed that female patients were associated with significantly longer survival times when compared with males (hazard ratio, 0.077; 95% confidence interval [CI], 0.007-0.083; P=0.035). One-year PFS and OS rates in CR, PR and SD patients were 77.8, 73.9 and 33.3%, and 89.2, 79.8 and 33.7%, respectively, although neither difference was identified to be statistically significant. In addition, the median OS of SD patients was 12 months (95% CI, 7.2-16.8 months). Brain metastasis was the major site of disease progression (23.1%). Gefitinib treatment for patients with lung adenocarcinoma showed a marked long-term survival benefit, even in SD patients. However, further studies are required to analyze the efficacy of gefitinib in penetrating the blood-brain barrier in order to prolong PFS in patients with lung adenocarcinoma.

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Dataset Information

[Expression of transcription factor SOX12 in lung adenocarcinoma and its clinical significance].

Publications

[Expression of transcription factor SOX12 in lung adenocarcinoma and its clinical significance].

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