Prognostic value of high FoxC2 expression in resectable non-small cell lung cancer, alone or in combination with E-cadherin expression

Jiang, Wei; Fan, Hong; Qian, Cheng; Ding, Jianyong; Wang, Qun; Pang, Xuguang

doi:10.1186/s12885-016-2056-0

Cited by 28 publications

(29 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This discrepancy might be due to the complex role of E-cadherin in metastasis or the different responses of cells which are treated with stimuli. However, most studies indicate that the reduction of E-cadherin expression in lung cancer cells is associated with low tumor differentiation, high metastasis, and poor outcome [46, 47]. Our data affirm these results and indicate a new TGF-β-miR-193a-E-cadherin pathway to promote TGF-β-induced EMT in lung cancer.…”

Section: Discussionsupporting

confidence: 87%

Pathologically decreased expression of miR-193a contributes to metastasis by targeting WT1-E-cadherin axis in non-small cell lung cancers

Chen

Gao

Wang

et al. 2016

J Exp Clin Cancer Res

View full text Add to dashboard Cite

BackgroundThe metastatic cascade is a complex and multistep process with many potential barriers. Recently, miR-193a has been reported to be a suppressive miRNA in multiple types of cancers, but its underlying anti-oncogenic activity in non-small cell lung cancers (NSCLC) is not fully elucidated.MethodsThe expressions of miR-193a (miR-193a-5p) in human lung cancer tissues and cell lines were detected by real-time PCR. Dual-luciferase reporter assay was used to identify the direct target of miR-193a. Cell proliferation, apoptosis, and metastasis were assessed by CCK-8, flow cytometry, and Transwell assay, respectively.ResultsThe expression of miR-193a in lung cancer tissues was decreased comparing to adjacent non-tumor tissues due to DNA hypermethylation in lung cancer tissues. Ectopic expression of miR-193a inhibited cell proliferation, colony formation, migration, and invasion in A549 and H1299 cells. Moreover, overexpression of miR-193a partially reversed tumor growth factor-β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) in NSCLC cells. Mechanistically, miR-193a reduced the expression of WT1, which negatively regulated the protein level of E-cadherin, suggesting that miR-193a might prevent EMT via modulating WT1-E-cadherin axis. Importantly, knockdown of WT1 resembled the anti-cancer activity by miR-193a and overexpression of WT1 partially reversed miR-193a-induced anti-cancer activity, indicating that WT1 plays an important role in miR-193a-induced anti-cancer activity. Finally, overexpression of miR-193a decreased the growth of tumor xenografts in mice.ConclusionCollectively, our results have revealed an important role of miR-193a-WT1-E-cadherin axis in metastasis, demonstrated an important molecular cue for EMT, and suggested a therapeutic strategy of restoring miR-193a expression in NSCLC.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0450-8) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionsupporting

confidence: 87%

Pathologically decreased expression of miR-193a contributes to metastasis by targeting WT1-E-cadherin axis in non-small cell lung cancers

Chen

Gao

Wang

et al. 2016

J Exp Clin Cancer Res

View full text Add to dashboard Cite

show abstract

“…However, in addition to lymphatics, these protein are expressed in various cell types and contribute to multiple molecular processes, including those in malignancies, as it has been demonstrated in a number of recent comprehensive reviews (54)(55)(56)(57)(58)(59)(60)(61)(62). This may provide an explanation for inconsistent data on the expression of analyzed proteins in cancer and their impact on tumor progression and clinical outcome (63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77).…”

Section: Discussionmentioning

confidence: 98%

Lymphatics-associated genes are downregulated at transcription level in non-small cell lung cancer

Kowalczuk

Laudański

et al. 2018

Oncol Lett

View full text Add to dashboard Cite

The present study aimed to verify a possibility of ongoing lymphangiogenesis in non-small cell lung cancer (NSCLC) via examination of mRNA levels of a number of lymphangiogenesis-associated genes in tumors. It was hypothesized that transcriptional activation of these genes would occur in tumors that stimulate new lymphatic vessel formation. The study was performed on 140 pairs of fresh-frozen surgical specimens of cancer and unaffected lung tissues derived from NSCLC stage I-IIIA patients. mRNA levels were evaluated with the reverse transcription-quantitative polymerase chain reaction method and expressed as fold change differences between the tumor and normal tissues. Possible associations between expression and patient clinicopathological characteristics and survival were analyzed. In the NSCLC tissue samples, vascular endothelial growth factor (VEGF) C, VEGFD, VEGFR3, VEGFR2, VEGFR1, lymphatic vessel endothelial hyaluronan receptor 1, integrin subunit α 9, FOX2, neuropilin 2, fibroblast growth factor 2 genes were significantly downregulated (P<0.001 for all) compared with matched normal lung tissues, whereas mRNA levels for VEGFA, spleen associated tyrosine kinase, podoplanin, and prospero homeobox 1 genes were similar in both tissues. Neither lymph node status, nor disease pathological stage influenced expression, whereas more profound suppression of gene activities appeared to occur in squamous cell carcinomas compared with adenocarcinomas. The VEGFR1 mRNA expression level was significantly connected with patient survival in the univariate analysis, and was an independent prognostic factor for overall survival in the multivariate Cox's proportional hazards model (HR 2.103; 95% confidence interval: 1.005-4.401; P=0.049). The results support a hypothesis of absence of new lymphatic vessel formation inside growing NSCLC tumor mass, however do not exclude a possibility of lymphangiogenesis in narrow marginal tumor parts.

show abstract

“…Previous studies on E-Cadherin expression in NSCLC tested by immunohistochemistry report conserved protein expression ranging from 32% to 88% in tumors depending on the IHC cutoff value. [22][23][24][25][26][27][28][29] Moreover, an association of E-Cadherin loss of IHC expression and the N+ status of patients was reported in several stages I to IV NSCLC cohorts. 23,24,[28][29][30][31][32][33] Two other studies that analyzed CDH1 expression in stage I to III NSCLC tumors reported an opposite association between CDH1 expression and N status, with one study reporting preserved CDH1 expression and the other study reporting lost CDH1 expression.…”

Section: Discussionmentioning

confidence: 99%

SNAI2 and TWIST1 in lymph node progression in early stages of NSCLC patients

et al. 2018

View full text Add to dashboard Cite

Lymph node metastasis is an important prognosis factor in non‐small cell lung cancer (NSCLC) patients. The aim of this study was to investigate the role of epithelial to mesenchymal transition (EMT) in lymph node progression in the early stages of NSCLC. We studied a retrospective cohort of 160 consecutive surgically treated NSCLC patients with available frozen tumor samples for expression of EMT markers (CDH1, CTNNB1, CDH2, and VIMENTIN), inducers (TGFB1, c‐MET, and CAIX), and transcription factors (EMT‐TF:SNAI1, SNAI2, ZEB1, TWIST1, and TWIST2). Partial EMT was more frequent in N1‐2 (N+) vs N0 patients (P < .01). TGFB1 (P = .02) as well as SNAI2 (P < .01) and TWIST1 (P = .04) were the most differentially expressed genes in N+ tumors. In this group, ZEB1 was correlated with all EMT inducers and other EMT‐TFs were overexpressed depending on the inducers. CAIX was an independent prognostic factor for overall survival (IC 95% HR: 1.10‐5.14, P = .03). Partial EMT is involved in lymph node progression of NSCLC patients and depends on the TGFβ pathway. EMT‐TFs are differentially expressed depending on EMT inducers. CAIX might be a relevant prognostic marker in early stage NSCLC.

show abstract

Prognostic value of high FoxC2 expression in resectable non-small cell lung cancer, alone or in combination with E-cadherin expression

Cited by 28 publications

References 23 publications

Pathologically decreased expression of miR-193a contributes to metastasis by targeting WT1-E-cadherin axis in non-small cell lung cancers

Pathologically decreased expression of miR-193a contributes to metastasis by targeting WT1-E-cadherin axis in non-small cell lung cancers

Lymphatics-associated genes are downregulated at transcription level in non-small cell lung cancer

SNAI2 and TWIST1 in lymph node progression in early stages of NSCLC patients

Contact Info

Product

Resources

About