Prognostic Values of Vimentin Expression and Its Clinicopathological Significance in Non-Small Cell Lung Cancer: A Meta-Analysis of Observational Studies with 4118 Cases

<div><p>Background</p><p>Vimentin is a member of the intermediate filament proteins and a canonical marker of the epithelial-mesenchymal transition (EMT), which is pivotal in tumorigenesis, metastasis and invasion in non-small cell lung cancer (NSCLC). The current meta-analysis aimed to investigate the associations between vimentin and prognosis and progression in NSCLC.</p><p>Methods</p><p>Databases with literature published in English, including PubMed, Web of Science, Embase, Science Direct, Wiley Online Library, Ovid, Cochrane Central Register of Controlled Trials, LILACS and Google Scholar, and the CNKI, VIP, CBM and WanFang databases in Chinese were used for the literature search. The key terms included (1) ‘vimentin’ OR ‘vim’ OR ‘vmt’ OR ‘vm’ OR ‘hel113’ OR ‘ctrct30’ and (2) ‘pulmon*’ OR ‘lung’ OR ‘alveolar’ and (3) ‘cancer’ OR ‘carcinoma’ OR ‘tumor’ OR ‘adenocarcinoma’ OR ‘squamous’ OR ‘neoplas*’ OR ‘malignan*’. The data were combined by random effect model and the H value and I² were used to assess the heterogeneity. All the meta-analysis was conducted using Stata 12.0.</p><p>Results</p><p>Thirty-two qualified studies (4118 cases) were included in the current meta-analysis. Twelve studies with 1750 patients were included to assess the significance of vimentin in the overall survival (OS) of NSCLC; the pooled hazard ratio (HR) was 1.831 (confidence interval (CI): 1.315–2.550, P<0.001) in the univariate analysis and 1.266 (CI: 0.906–1.768, P = 0.167) in the multivariate analysis. Four studies with 988 cases were applicable to determine the significance of vimentin in the disease-free survival (DFS) of NSCLC; the pooled HR of the DFS was 1.224 (CI: 0.921–1.628, P = 0.164) in the univariate analysis and 1.254 (CI: 0.985–1.956, P = 0.067) in the multivariate analysis. Regarding the relationships between vimentin and clinicopathological factors, the pooled odds ratio (OR) with 3406 NSCLCs indicated that up-regulated vimentin was associated with smoking (OR = 1.359, CI: 1.098–1.683, P = 0.004), poor differentiation (OR = 2.133, CI: 1.664–2.735, P<0.001), an advanced TNM stage (OR = 3.275, CI: 1.987–5.397, P<0.001), vascular invasion (OR = 3.492, CI: 1.063–11.472, P = 0.039), lymph node metastasis (OR = 2.628, CI: 1.857–3.718, P<0.001), recurrence (OR = 1.631, CI: 1.052–2.528, P = 0.029) and pleural invasion (OR = 2.346, CI: 1.397–3.941, P = 0.001). There was no significant correlation between vimentin and age, gender, diameter, T stage, distant metastasis, or marginal invasion (P>0.05).</p><p>Conclusion</p><p>An overexpression of vimentin may predict the progression and an unfavorable survival of NSCLC. Vimentin may represent a helpful biomarker and a potential target for the treatment strategies of NSCLC. Additional, prospective studies with large samples are necessary to confirm the significance of vimentin in NSCLC.</p></div

Flow chart of literature search.

<p>Flow chart of literature search.</p

Sensitivity analyses of included studies.

<p>(a) OS in univariate analysis, (b) OS in multivariate analysis, (c) DFS in univariate analysis, and (d) DFS in multivariate analysis.</p

Subgroup analysis of HR in overall survival (OS) by univariate and multivariable analyses.

<p>Subgroup analysis of HR in overall survival (OS) by univariate and multivariable analyses.</p

Characteristics of the included studies for the overall survival (OS) analysis.

<p>Characteristics of the included studies for the overall survival (OS) analysis.</p

Characteristics of the included studies for the disease-free survival (DFS) analysis.

<p>Characteristics of the included studies for the disease-free survival (DFS) analysis.</p

Analysis of relationships between vimentin and clinicopathological variables in NSCLC.

<p>Analysis of relationships between vimentin and clinicopathological variables in NSCLC.</p

Forest plots of vimentin expression and OS rate in NSCLC via univariate and multivariate analyses.

<p>Forest plots of vimentin expression and OS rate in NSCLC via univariate and multivariate analyses.</p

Forest plots of ORs for associations between vimentin and clinicopathological characteristics in NSCLC.

<p>(a) Vascular invasion, (b) Lymph node metastasis, (c) Recurrence, and (d) Pleural invasion.</p

Table5_Mitochondria-associated gene expression perturbation predicts clinical outcomes and shows potential for targeted therapy in neuroblastoma.docx

BackgroundMitochondria have long been considered a potential target in cancer therapy because malignant cells are known for their altered energy production. However, there is a lack of comprehensive research on the involvement of mitochondria-associated proteins (MAPs) in neuroblastoma (NB), and their potential as therapeutic targets is yet to be fully explored.MethodsMAP genes were defined based on the protein-coding genes with mitochondrial localization. The mRNA expression patterns and dynamics of MAP genes associated with NB were investigated by integrating publicly available transcriptional profiles at the cellular and tissue levels. Multivariate Cox regression analysis was conducted to reveal the association of MAP genes with the overall survival (OS) and clinical subgroups of NB patients. The single-cell RNA-seq dataset and gene dependency screening datasets were analyzed to reveal the therapeutic potential of targeting MAP genes.ResultsWe compiled a total of 1,712 MAP genes. We found the global and cell type-specific mRNA expression changes of the MAP genes associated with NB status and survival. Our analyses revealed a group of MAP gene signatures independent of MYCN-amplification status associated with NB outcome. We provided computational evidence with selected MAP genes showing good performance in predicting long-term prognosis. By analyzing gene dependency of the MAP genes in NB cell lines and ex vivo human primary T cells, we demonstrated the therapeutic potential of targeting several MAP genes in NB tumors.ConclusionsCollectively, our study provides evidence for the MAP genes as extended candidates in NB tumor stratification and staging, prognostic prediction, and targeted drug development.</p