Progression-free survival (PFS) and overall survival (OS) of patients with activated B-cell-like diffuse large B-cell lymphoma with or without A20 mutations.

<p>Progression-free survival (PFS) and overall survival (OS) of patients with activated B-cell-like diffuse large B-cell lymphoma with or without A20 mutations.</p

Prognostic Value of MET Gene Copy Number and Protein Expression in Patients with Surgically Resected Non-Small Cell Lung Cancer: A Meta-Analysis of Published Literatures

<div><p>Background</p><p>The prognostic value of the copy number (GCN) and protein expression of the mesenchymal-epithelial transition (MET) gene for survival of patients with non-small cell lung cancer (NSCLC) remains controversial. This study aims to comprehensively and quantitatively asses the suitability of MET GCN and protein expression to predict patients' survival.</p><p>Methods</p><p>PubMed, Embase, Web of Science and Google Scholar were searched for articles comparing overall survival in patients with high MET GCN or protein expression with those with low level. Pooled hazard ratio (HR) and 95% confidence intervals (CIs) were calculated using the random and the fixed-effects models. Subgroup and sensitivity analyses were also performed.</p><p>Results</p><p>Eighteen eligible studies enrolling 5,516 patients were identified. Pooled analyses revealed that high MET GCN or protein expression was associated with poor overall survival (OS) (GCN: HR = 1.90, 95% CI 1.35–2.68, <i>p</i><0.001; protein expression: HR = 1.52, 95% CI 1.08–2.15, <i>p</i> = 0.017). In Asian populations (GCN: HR = 2.22, 95% CI 1.46–3.38, <i>p</i><0.001; protein expression: HR = 1.89, 95% CI 1.34–2.68, <i>p</i><0.001), but not in the non-Asian subset. For adenocarcinoma, high MET GCN or protein expression indicated decreased OS (GCN: HR = 1.49, 95% CI 1.05–2.10, <i>p</i> = 0.025; protein expression: HR = 1.69, 95% CI 1.31–2.19, <i>p</i><0.001). Results were similar for multivariate analysis (GCN: HR = 1.61, 95% CI 1.15–2.25, <i>p</i> = 0.005; protein expression: HR = 2.18, 95% CI 1.60–2.97, <i>p</i><0.001). The results of the sensitivity analysis were not materially altered and did not draw different conclusions.</p><p>Conclusions</p><p>Increased MET GCN or protein expression was significantly associated with poorer survival in patients with surgically resected NSCLC; this information could potentially further stratify patients in clinical treatment.</p></div

Evaluation of human mesenchymal-epithelial transition (MET) by immunohistochemistry (IHC) in the selected studies in the selected studies.

<p>NA: not available; NSCLC, non-small cell lung cancer; ADC, adenocarcinoma; IHC, immunohistochemistry; HR: hazard ratio, obtained by estimated (E) or reported in text (R). “M” means the HR come from multivariate analysis, and “U” means HR come from univariate analysis; EGFR, epidermal growth factor receptor; HGF, hepatocyte growth factor.</p

Main meta-analysis results.

<p>N: number of studies; HR: hazard ratio; RT-PCR, real-time polymerase chain reaction; FISH, fluorescent in situ hybridization; SISH, silver in situ hybridization; BISH, bright-field in situ hybridization; IHC, immunohistochemistry; NSCLC, non-small cell lung cancer; ADC, adenocarcinoma; SCC, squamous cell carcinoma; EGFR, epidermal growth factor receptor; WT, wild type.</p

Evaluation of human mesenchymal-epithelial transition (MET) gene copy number in the selected studies.

<p>NA: not available; NSCLC, non-small cell lung cancer; ADC, adenocarcinoma; SCC, squamous cell carcinoma; RT-PCR, real-time polymerase chain reaction; FISH, fluorescent in situ hybridization; SISH, silver in situ hybridization; BISH, bright-field in situ hybridization; IHC, immunohistochemistry; Cappuzzo scoring system: MET FISH-positive group was defined mean MET gene copy number≥5 copies per cell; UCCC criteria: the University of Colorado Cancer Center) criteria, MET gene status was classified into two groups according to the frequency of tumor cells with specific copy numbers of the MET gene and the chromosome 7 centromere: FISH-positive MET MET to CEP7 ratio ≥2; >15 copies of the MET signals in >10% of tumor cells; small gene cluster [4–10 copies]; or innumerable tight gene clusters in >10% the tumor cells); EGFR, epidermal growth factor receptor; HR: hazard ratio, obtained by estimated (E) or reported in text (R). “M” means the HR come from multivariate analysis, and “U” means HR come from univariate analysis.</p

Meta-analysis of effects of the MET gene copy number on overall survival of patients with non-small cell lung cancer (NSCLC).

<p>Forest plot showing (A) the combined relative HR for OS by univariate analysis; (B) the combined relative HR for OS by multivariate analysis.</p

Forest plot (A) assessing MET gene copy number in NSCLC stratified by histological subtypes; Forest plot (B) assessing MET gene copy number in NSCLC stratified by ethnic source.

<p>Forest plot (A) assessing MET gene copy number in NSCLC stratified by histological subtypes; Forest plot (B) assessing MET gene copy number in NSCLC stratified by ethnic source.</p

Meta-analysis of effects of the MET protein expression on overall survival of patients with NSCLC.

<p>Forest plot showing (A) the combined relative HR for OS by univariate analysis; (B) the combined relative HR for OS by multivariate analysis.</p

Forest plot (A) assessing MET protein expression in NSCLC stratified by histological subtypes; Forest plot (B) assessing MET protein expression in NSCLC stratified by ethnic source.

<p>Forest plot (A) assessing MET protein expression in NSCLC stratified by histological subtypes; Forest plot (B) assessing MET protein expression in NSCLC stratified by ethnic source.</p

Table3_Gene set-based identification of two immune subtypes of diffuse large B cell lymphoma for guiding immune checkpoint blocking therapy.XLSX

Background: Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma in adults. Tumour microenvironment is closely related to tumour prognosis and immune checkpoint blocking therapy (ICBT). This study aimed to investigate the immunological and prognostic characteristics of the tumour microenvironment (TME), as well as the regulatory mechanisms.Methods: Gene expression profiles and clinical data of patients with DLBCL were obtained from GEO database. ESTIMATE, CIBERSORT, and ssGSEA analyses were used to explore microenvironment characteristics and regulatory mechanism of the immune subtypes, which were identified by consistent clustering. The differences in enriched pathways were showed by GSEA. Hub genes associated with CD8+ T cells, which were identified by WCGNA, were exhibited biological functions through GO and KEGG. Immune-related gene scores (IRGSs) based on hub genes were used to evaluate the prediction of immune subtypes and ICBT, and retrospective analysis was used for validation. Finally, prognostic genes were screened to construct risk models.Results: Consensus clustering divided patients with DLBCL into two subtypes with significant heterogeneities in prognosis and immune microenvironment. Low immune infiltration was associated with poor prognosis. Subtype C1 with high immune infiltration was enriched in multiple immune pathways. We observed that two common mutated genes (B2M and EZH2) in DLBCL were closely related to MHC-I and microenvironment. Our further analysis manifested that MYD88L265P may be the main cause of TLR signalling pathway activation in subtype C1. Hub genes (SH2D1A, CD8A, GBP2, ITK, CD3D, RORA, IL1R2, CD28, CD247, CD3G, PRKCQ, CXCR6, and CD3E) in relation with CD8+ T cells were used to establish IRGS, which was proved an accurate predictor of immune subtypes, and patients in high-IRGS group were more likely to benefit from ICBT. Retrospective analysis showed that absolute lymphocyte count (ALC) was higher in the group that responded to the PD-1 inhibitor. Finally, the risk model was constructed based on two genes (CD3G and CD3D), and the low-risk group showed better prognosis.Conclusion: DLBCL immune classifications with highly heterogeneity are a powerful predictor of prognosis and ICBT. The IRGS is proved to be a reliable tool to distinguish immune subtypes as a substitute for gene expression profile.</p