Dataset Information

Low-expression of TMEM100 is associated with poor prognosis in non-small-cell lung cancer.

ABSTRACT: Transmembrane protein 100 (TMEM100) was first identified as a transcript from the mouse genome. Recent studies have demonstrated that TMEM100 is involved in hepatocellular carcinoma (HCC) malignancy. However, the distribution and clinical significance of TMEM100 in non-small-cell lung carcinoma (NSCLC) remains poorly understood. This study aims to explore the significance of TMEM100 expression in NSCLC. We found that TMEM100 expression was significantly reduced in NSCLC tissues when compared with that in adjacent normal lung tissues (P<0.001). Kaplan-Meier survival analysis showed that overall survival of patients with lower expressions of TMEM100 was significantly shorter (n=152, P<0.05). In addition, TMEM100 overexpression in NSCLC cell lines inhibited cell proliferation in vitro and in vivo. Transwell migration and invasion assay showed that TMEM100 significantly suppressed the migration and invasion of NSCLC cell lines. In contrast, knocking down TMEM100 promoted NSCLC proliferation and migration. Finally, we found that TMEM100 worked as a cancer suppressor gene mainly by inhibiting the TNF signaling pathway. In conclusion, TMEM100 acted as a tumor suppressor in NSCLC and may prove to be a potential prognostic biomarker and therapeutic target for NSCLC.

SUBMITTER: Han Z

PROVIDER: S-EPMC5446537 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Low-expression of TMEM100 is associated with poor prognosis in non-small-cell lung cancer.

Han Zhitao Z Wang Ting T Han Shuai S Chen Yuanming Y Chen Tianrui T Jia Qi Q Li Bo B Li Binbin B Wang Jing J Chen Guanghui G Liu Ge G Gong Haiyi H Wei Haifeng H Zhou Wang W Liu Tielong T Xiao Jianru J

American journal of translational research 20170515 5

Transmembrane protein 100 (TMEM100) was first identified as a transcript from the mouse genome. Recent studies have demonstrated that TMEM100 is involved in hepatocellular carcinoma (HCC) malignancy. However, the distribution and clinical significance of TMEM100 in non-small-cell lung carcinoma (NSCLC) remains poorly understood. This study aims to explore the significance of TMEM100 expression in NSCLC. We found that TMEM100 expression was significantly reduced in NSCLC tissues when compared wit ...[more]

PMID: 28560005

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Project description:BackgroundKaiso has been identified as a new member of the POZ-zinc finger family of transcription factors that are implicated in development and cancer. Although controversy still exists, Kaiso is supposed to be involved in human cancer. However, there is limited information regarding the clinical significance of cytoplasmic/nuclear Kaiso in human lung cancer.MethodsIn this study, immunohistochemical studies were performed on 20 cases of normal lung tissues and 294 cases of non-small cell lung cancer (NSCLC), including 50 cases of paired lymph node metastases and 88 cases with complete follow-up records. Three lung cancer cell lines showing primarily nuclear localization of Kaiso were selected to examine whether roles of Kaiso in cytoplasm and in nucleus are identical. Nuclear Kaiso was down-regulated by shRNA technology or addition a specific Kaiso antibody in these cell lines. The proliferative and invasive abilities were evaluated by MTT and Matrigel invasive assay, transcription of Kaiso's target gene matrilysin was detected by RT-PCR.ResultsKaiso was primarily expressed in the cytoplasm of lung cancer tissues. Overall positive cytoplasmic expression rate was 63.61% (187/294). The positive cytoplasmic expression of Kaiso was higher in advanced TNM stages (III+IV) of NSCLC, compared to lower stages (I+II) (p = 0.019). A correlation between cytoplasmic Kaiso expression and lymph node metastasis was found (p = 0.003). In 50 paired cases, cytoplasmic expression of Kaiso was 78.0% (41/50) in primary sites and 90.0% (45/50) in lymph node metastases (p = 0.001). The lung cancer-related 5-year survival rate was significantly lower in patients who were cytoplasmic Kaiso-positive (22.22%), compared to those with cytoplasmic Kaiso-negative tumors (64.00%) (p = 0.005). Nuclear Kaiso staining was seen in occasional cases with only a 5.10% (15/294) positive rate and was not associated with any clinicopathological features of NSCLC. Furthermore, after the down-regulation of the nuclear expresses Kaiso in vitro, both proliferative and invasive abilities of three cancer cell lines were significantly enhanced, along with the up-regulation of Kaiso target gene, matrilysin.ConclusionOur data suggest cytoplasmic Kaiso expression is associated with poor prognosis of NSCLC and various subcellular localizations of Kaiso may play differential biological roles in NSCLC.

Project description:Background:We previously showed that ?3?1 integrin is a novel cancer biomarker and drug target in non-small cell lung cancer (NSCLC). This study characterized the integrin ?3 (ITGA3) expression on patient specimens. Methods:Tissue microarrays (TMAs) were prepared from archival tissue blocks containing 161 patients, which included 91 adenocarcinoma (LUAD), 46 squamous carcinomas (LUSC), and 24 other histology types. TMA sections were stained and scored for ITGA3 expression by immunohistochemistry (IHC). Kaplan-Meier curves and log-rank tests were used to compare overall survival (OS) between IHC score groups. Propensity-score-weighted Kaplan-Meier curves and weighted Cox models were used to adjust for covariate imbalance between IHC score groups. Logistic regression was used to determine ITGA3 transcriptome expression in NSCLC in The Cancer Genome Atlas (TCGA). Results:ITGA3 IHC expression (1+ to 3+) was detected in 107/161 (66.5%) of the NSCLC samples, and was associated with poor prognosis at the edge of significance (HR =1.30, 95% CI: 0.99-1.71, P=0.056), but significant (P<0.05) in subgroups of female patients, smokers and tumors with grade I and II differentiation using propensity-score-weighted survival analysis after adjusting for confounders. Multivariate survival analysis based on multiple imputation for missing variables showed ITGA3 expression, old age and metastasis were associated with poor prognosis (P<0.05). ITGA3 IHC expression was associated with poor prognosis in LUSC (HR =2.27, P<0.05) but not in LUAD (HR =1.49, P=0.16). Median ITGA3 expression was significantly higher in LUAD than LUSC (P<0.0001) in the TCGA transcriptome datasets. Using a higher cutoff than LUSC (70.6 vs. 19.5 FPKM), high ITGA3 RNA expression was also associated with poor prognosis in LUAD (P=0.023). ITGA3 interacted with key genes regulating epithelial to mesenchymal transition, angiogenesis, invasion and metastasis in both LUAD and LUSC. Conclusions:High ITGA3 IHC expression was associated with poor prognosis in NSCLC patients. Further study is warranted for targeting ?3?1 integrin in NSCLC.

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Low-expression of TMEM100 is associated with poor prognosis in non-small-cell lung cancer.

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Low-expression of TMEM100 is associated with poor prognosis in non-small-cell lung cancer.

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