Univariate and multivariate Cox regression analysis.

<p>Univariate and multivariate Cox regression analysis.</p

Heterogeneity of CTC sub-populations according to CellSearch positivity before treatment initiation.

<p>Heterogeneity of CTC sub-populations according to CellSearch positivity before treatment initiation.</p

Kaplan Meier curves for PFS and OS.

<p>(a) Probability of PFS according to the detection of CTC at baseline by the CellSearch, (b) Probability of OS according to the detection of CTC on disease progression by the CellSearch, (c) Probability of OS according to the detection of EMT phenotype expression at baseline and (e) Probability of OS according to the detection of apoptotic phenotype on disease progression.</p

Clinical characteristics of SCLC patients.

<p>Clinical characteristics of SCLC patients.</p

Detection of different sub-populations of CTCs during treatment.

<p>Detection of different sub-populations of CTCs during treatment.</p

Predictive Value of BRCA1, ERCC1, ATP7B, PKM2, TOPOI, TOPΟ-IIA, TOPOIIB and C-MYC Genes in Patients with Small Cell Lung Cancer (SCLC) Who Received First Line Therapy with Cisplatin and Etoposide

<div><p>Background</p><p>The aim of the study was to evaluate the predictive value of genes involved in the action of cisplatin-etoposide in Small Cell Lung Cancer (SCLC).</p> <p>Methods</p><p>184 SCLC patients’ primary tumour samples were analyzed for <i>ERCCI, BRCA1, ATP7B, PKM2</i><i>TOPOI, TOPOIIA</i>, <i>TOPOIIB</i> and <i>C-MYC</i> mRNA expression. All patients were treated with cisplatin-etoposide.</p> <p>Results</p><p>The patients’ median age was 63 years and 120 (65%) had extended stage, 75 (41%) had increased LDH serum levels and 131 (71%) an ECOG performance status was 0-1. Patients with limited stage, whose tumours expressed high <i>ERCC1</i> (<i>p</i>=0.028), <i>PKM2</i> (<i>p</i>=0.046), <i>TOPOI</i> (<i>p</i>=0.008), <i>TOPOIIA</i> (<i>p</i>=0.002) and <i>TOPOIIB</i> (p<0.001) mRNA had a shorter Progression Free Survival (PFS). In limited stage patients, high expression of <i>ERCC1</i> (<i>p</i>=0.014), <i>PKM2</i> (<i>p</i>=0.026), <i>TOPOIIA</i> (<i>p</i>=0.021) and <i>TOPOIIB</i> (<i>p</i>=0.019) was correlated with decreased median overall survival (mOS) while in patients with extended stage, only high <i>TOPOIIB</i> expression had a negative impact on Os (<i>p</i>=0.035). The favorable expression signature expression signature (low expression of <i>ERCC1</i>, PKM2, <i>TOPOIIA</i> and <i>TOPOIIB</i>) was correlated with significantly better PFS and Os in both LS-SCLC (<i>p</i><0.001 and <i>p</i>=0.007, respectively) and ES-SCLC (<i>p</i>=0.007 and (<i>p</i>=0.011, respectively) group. The unfavorable expression signature was an independent predictor for poor PFS (HR: 3.18; <i>p</i>=0.002 and HR: 3.14; <i>p</i>=0.021) and Os (HR: 4.35; <i>p=</i>0.001and HR: 3.32; <i>p</i>=0.019) in both limited and extended stage, respectively.</p> <p>Conclusions</p><p>Single gene’s expression analysis as well as the integrated analysis of <i>ERCC1</i>, <i>PKM2, TOPOIIA</i> and <i>TOPOIIB</i> may predict treatment outcome in patients with SCLC. These findings should be further validated in a prospective study.</p> </div

Overall Survival in Limited Stage-SCLC.

<p>A. <i>ERCC1</i> mRNA levels and Overall Survival in Limited Stage-SCLC. B. <i>PKM2</i> mRNA levels and Overall Free Survival in Limited Stage-SCLC. C. <i>TOPOIIA</i> mRNA levels and Overall Free Survival in Limited Stage-SCLC. <i>D</i>. <i>TOPOIIB</i> mRNA levels and Overall Free Survival in Limited Stage-SCLC. E. <i>TOPOIIB</i> mRNA levels and Overall Free Survival in Extended Stage-SCLC.</p

Predictive value of the expression signature (favorable: low <i>ERCC1, PKM2, TOPOIIA</i> and <i>TOPOIIB</i> mRNA levels) in SCLC.

<p>A. Correlation of expression signature with Progression Free Survival in Limited Stage-SCLC. B. Correlation of expression signature with Overall Survival in Limited Stage-SCLC. C. Correlation of expression signature with Progression Free Survival in Extended Stage-SCLC. D. Correlation of expression signature with Overall Survival in Extended Stage-SCLC.</p

Additional file 1: Figure S1. of Upregulation of citrullination pathway: From Autoimmune to Idiopathic Lung Fibrosis

A representative immunoblot of PADI2 in three (3) control, six (6) IPF and six (6) RA-ILD subjects. PADI2 protein correspond to the 72kDA band observed. (DOCX 11 kb