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C. Camps



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    MO05 - Prognostic and Predictive Biomarkers II (ID 95)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO05.09 - Activation of the classical complement pathway: a novel biomarker for the early diagnosis and prognosis of lung cancer (ID 964)

      17:05 - 17:10  |  Author(s): C. Camps

      • Abstract
      • Presentation
      • Slides

      Background
      Numerous diagnostic and prognostic molecular markers have been proposed for lung cancer. However, genetic heterogeneity has limited the success of these initiatives. This limitation may be overcome by the use of biomarkers related to the host response to cancer. In this study we tested the capacity of lung cancer cells to activate the complement system and evaluated the diagnostic performance of complement-activation fragments. We demonstrate for the first time that lung cancer cells efficiently activate the classical complement pathway and that fragments of complement activation are of value for detection and prognosis of lung cancer at a very early stage.

      Methods
      We first assessed complement activation in bronchial epithelial and lung cancer cell lines. C4d, a degradation product of complement activation, was determined in 90 primary lung tumors; in bronchoalveolar lavage supernatants from 50 patients with lung cancer and 22 non-malignant respiratory diseases; and in plasma samples from different cohorts, including: advanced (n=133) and early (n=84) non-small cell lung cancer patients, subjects with inflammatory lung diseases (n=133) and asymptomatic individuals enrolled in a lung cancer CT-screening program (n=190; 32 of them with lung cancer).

      Results
      Lung cancer cells treated with normal human serum activated complement and deposited C3 more efficiently than non-malignant bronchial epithelial cells. Incubation of cells with different buffer conditions, complement depleted sera and complement inhibitors showed that lung cancer cells bind C1q and activate complement through the classical complement pathway. In a set of lung cancer cell lines, a significant correlation was found between C1q binding and C4 or C3 deposition. The presence of phosphatidylserine inhibited C1q binding and diminished complement activation. Based on these results, C4d, a classical pathway-derived split product, was evaluated as a possible diagnostic or prognostic biomarker in lung cancer. Many lung primary tumors (adenocarcinomas and squamous cell carcinomas) deposited C4d. More importantly, survival was decreased in patients with high C4d deposition in their tumors (HR=3.06; 95% CI=1.18-7.91). Moreover, C4d levels were increased in bronchoalveolar lavage fluid from lung cancer patients as compared to patients with non-malignant respiratory diseases (0.61 ± 0.87 vs. 0.16 ± 0.11 µg/ml, respectively; P<0.001). C4d levels in plasma samples from lung cancer patients at both advanced (III and IV) and early (I and II) stages were also increased compared with control subjects (4.13 ± 2.02 vs. 1.86 ± 0.95 µg/ml, P<0.001; and 3.18 ± 3.20 vs. 1.13 ± 0.69 µg/ml, P<0.001, respectively). In addition, C4d plasma levels were associated with shorter survival in patients at advanced (HR=1.59; 95% CI=0.97-2.60) and early stages (HR=5.57; 95% CI=1.60-19.39). Plasma C4d levels were dramatically reduced after surgical removal of lung tumors. Finally, plasma C4d levels were associated with increased lung cancer risk in asymptomatic individuals: OR=4.38; 95% CI=1.61-11.93.

      Conclusion
      Lung tumors activate the classical complement pathway and generate C4d, a stable complement split product. Moreover, C4d is increased in biological samples from lung cancer patients, is associated with poor prognosis, and may be of clinical value for the early detection of lung cancer.

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    MO16 - Prognostic and Predictive Biomarkers IV (ID 97)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO16.02 - Tumor and Stroma Treg markers in resectable NSCLC (ID 2753)

      16:20 - 16:25  |  Author(s): C. Camps

      • Abstract
      • Presentation
      • Slides

      Background
      Immunosuppressive regulatory T lymphocytes (Tregs) have been proved to play a critical role in immune tolerance to tumor. In this study we have analyzed several markers related to Tregs, in both tumor and stroma areas in patients with resectable NSCLC.

      Methods
      Tumor FFPE samples from 135 early-stage NSCLC patients were used in this retrospective study. The most representative areas of tumor cells and tumor stroma of each sample were carefully micro-dissected. RTqPCR using hydrolysis probes was performed to determine the expression of Treg markers such as: CD127, CD25, FOXP3, CTLA-4, IL-10, TGFB-1, LAG-3, GITR and TNF-a as well as CD4 and CD8. Relative gene expression was assessed using GAPDH and CDKN1B as endogenous controls and results were normalized against a human cDNA as a reference. FOXP3 protein expression was assessed by immunohistochemistry, in 80 of the 135 patients included in this study. The absolute number of FOXP3-positive lymphocytes was determined in both tumor and stroma areas by averaging the cell counts in 10 fields (400X). All statistical analyses were considered significant at p< 0.05.

      Results
      Gene expression analyses revealed an over-expression of CD25 (5.40X and 7.95X, respectively) and down-expression of CD127 (0.28X and 0.37X, respectively) in both, tumor and stroma. There was a tendency toward higher expression of FOXP3 (1.67X and 2.01X, respectively) and CTLA-4 (1.92X and 1.76X, respectively) as well. Paired Wilcoxon test showed significant gene expression differences between tumor and stroma in FOXP3 (p=0.006), CD25 (p<0.0001), CD4 (p<0.0001), CD8 (p=0.028), IL-10 (p<0.0001) and TGFB-1 (p<0.0001). Survival analyses revealed that patients with a “Treg profile” (↑CD25/↓CD127) had a reduced overall survival (OS), whilst those patients with higher levels of the ratio FOXP3 stroma/tumor had worse time to progression (TTP) (Table 1). Spearman test revealed a significant association between stromal FOXP3 expression levels and the number of FOXP3-positive lymphocytes (by IHC) in stroma, p=0.006. Moreover, chi-square test showed that patients with squamous cell carcinoma histology presented a higher number of FOXP3-positive lymphocytes than those patients with adenocarcinoma, p= 0.035. Table 1: OS for “Treg profile” and TTP for Ratio FOXP3 Stroma/Tumor

      OS
      Median (months) 95% CI p
      Others 74.33 65.96 - 82.69 0.003
      "Treg profile" 29.90 4.91 - 6.54
      TTP
      Median (months) 95% CI p
      ↓ Ratio FOXP3 Stroma/Tumor NR -- 0.040
      ↑ Ratio FOXP3 Stroma/Tumor 32.50 16.25- 48.74

      Conclusion
      Gene expression of Treg markers in tumor microenvironment seem to play an important prognostic role in early-stage NSCLC patients. Furthermore, preliminary IHC analysis indicated a correlation between mRNA and protein levels for FOXP3 in NSCLC patients. Supported in part, by grants PS09/01149, RD06/0020/1024 and RD12/0036/0025 from Red Temática de Investigación Cooperativa en Cáncer, Instituto de Salud Carlos III (ISCIII).

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    MO21 - Prognostic and Predictive Biomarkers V - EGFR (ID 98)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO21.05 - Integrated genomic analysis by whole exome and transcriptome sequencing of tumor samples from EGFR-mutant non-small-cell lung cancer (NSCLC) patients with acquired resistance to erlotinib. (ID 1426)

      10:50 - 10:55  |  Author(s): C. Camps

      • Abstract
      • Presentation
      • Slides

      Background
      NSCLC patients with EGFR mutations initially respond to EGFR tyrosine kinase inhibitors (TKIs) but ultimately relapse. Sub-genomic molecular studies indicate that the EGFR T790M mutation and the activation of MET, PI3K, AXL, HER2 and MAPK can lead to acquired resistance to EGFR TKIs. To date, no integrated comprehensive genomic investigation of EGFR TKI resistance has been reported.

      Methods
      FFPE biopsies of erlotinib-sensitive and erlotinib-resistant tumors were obtained from 13 EGFR mutant NSCLC patients. The samples were analyzed by whole exome sequencing and whole transcriptome sequencing utilizing the Illumina HiSeq2500 platform. In addition, targeted gene sequencing was performed with the Illumina TruSeq Amplicon-Cancer Panel and run on the MiSeq system.

      Results
      Erlotinib resistant NSCLC specimens harbored known resistance drivers, including EGFR T790M mutations (9/13; 69%), MET amplification (3/13; 23%), HER2 amplification (3/13; 23%), and AXL upregulation (3/13; 23%). Differential expression analysis between resistant and pre-treatment states revealed enrichment in the pre-treatment tumors of immune signaling pathways, and in the resistant tumors upregulation of ERBB2, mTOR, PI3 kinase and ribosomal signaling pathways. PI3K/AKT pathway upregulation also occurred through somatic mutations in AKT and LKB1 in the resistant tumors. Copy number analysis demonstrated both large scale and focal amplifications and deletions in the resistant tumors, including the focal loss of EGFR and gain of c-Myc and NKX2-1. There was strong correlation between the copy number changes observed and the expression mRNA levels of the involved cancer-associated genes. Of note, each resistant tumor exhibited greater copy number similarity to the corresponding matched pre-treatment sample compared to other tumors within the resistance cohort.

      Conclusion
      We conducted the first ever comprehensive integrated genomic analysis of EGFR TKI resistant NSCLC patients, and identified both known and potentially novel drivers of EGFR TKI resistance. This study demonstrated the feasibility and utility of comprehensive genomic analysis in the clinical management of NSCLC receiving targeted therapy. Together, our data provide unprecedented insight into the molecular pathogenesis of escape from EGFR oncogene inhibition in NSCLC. We are now conducting a prospective observational study in additional NSCLC patients on targeted therapy.

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    MO25 - NSCLC - Combined Modality Therapy II (ID 112)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Mesothelioma
    • Presentations: 1
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      MO25.01 - Interim analysis of the Spanish Lung Cancer Group (SLCG) randomized phase II trial of thoracic radiotherapy (RT) concurrent with cisplatin (P) plus oral vinorelbine (OV) or etoposide (E) for unresectable locally advanced (LA) stage III non-small cell lung cancer (NSCLC). (GECP10/02). (ID 2658)

      10:30 - 10:35  |  Author(s): C. Camps

      • Abstract
      • Presentation
      • Slides

      Background
      Chemoradiation is the standard of care for the treatment of unresectable LA-NSCLC. Cisplatin plus either etoposide or vinorelbine are two of the chemotherapy (CT) regimens widely used for the disease concurrently with radiotherapy. Oral vinorelbine is a formulation which has achieved comparable results to the IV vinorelbine. The purpose of the study is to evaluate the efficacy and safety of cisplatin when combined with etoposide or oral vinorelbine with radical radiation for the management of stage III NSCLC.

      Methods
      Patients (pts) between 18 and 75 years, with histologically proven untreated and unresectable LA stage IIIA/IIIB NSCLC, adequate bone marrow, hepatic and renal function, ECOG PS 0-1, were randomized to: Arm OV-P: OV 60 mg/m[2] D1, D8 cycle 1 and 80 mg/m[2] cycle 2 (if no grade 3-4 toxicity) plus P 80 mg/m[2] D1 every 3 weeks for 2 cycles as induction; patients without progression received OV 40 mg/m[2] D1, D8, and P 80 mg/m[2] D1 every 3 weeks for 2 more cycles (4 cycles in total). Arm E-P: E 50 mg/m[2] intravenously D1 to D5 plus P 50 mg/m[2] D1, D8 every 4 weeks for 2 cycles. Both regimens administered with concurrent RT 66 Gy in 6.5 weeks. The primary endpoint was progression free survival using RECIST 1.1, and secondary endpoints were overall response rate, overall survival, and safety profile. To guarantee an overall type-1 α error (one side) no greater than 0.05 and a type II (β) error 0.1 for the primary endpoint of PFS, a sample size of 134 pts allocated in a 1:1 ratio is planned.

      Results
      Since August 2011 77 pts have been recruited. 46 pts have been included in the interim analysis, 23 pts have been randomly allocated to each treatment arm. Patient’s characteristics were: Male 91.3%; median age 64 (range 44-75); PS1 56.5%; smokers 46.8%; adenocarcinoma 40.4% / squamous 55.3%; stage IIIA 46.8% / IIIB 53.2%. Median of months between initial diagnosis and study start was 1 (range 0.3-15.7). Safety: 118 cycles (cy) were analysed, 79 in arm OV-P and 39 in arm E-P. Hematological toxicities arms OV-P/E-P (% cy): grade (g) 3/4 neutropenia 8.9%/13.1%; g3 thrombocytopenia 0%/5.3%; g3 anemia 0%/2.6%; febrile neutropenia 3 cases on OV-P arm (all during induction CT on cy 1) and 1 case on E-P arm (during concurrent chemoradiation). Non-hematological toxicities arms OV-P/E-P (% cy): g3 esophagitis/mucositis 1.3%/15.5%; g3 infection without neutropenia 1.3%/5.1%. No treatment-related deaths were reported. There was no remarkable difference in other toxicities between both arms. 39 pts completed the treatment as per protocol, 19 in arm OV-P and 20 in arm E-P. Overall response rates were 73.7% and 50% for the OV-P and the E-P arm, respectively.

      Conclusion
      This interim analysis shows that OV-P and E-P when administered concurrently with RT have a manageable safety profile with efficacy. Safety data is consistent with other studies reported for both chemoradiation regimens. Based on these positive results for safety, accrual is ongoing. Clinical trial information EudraCT 2010-022927-31.

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    O15 - NSCLC - Chemotherapy II (ID 109)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      O15.02 - The Spanish Lung Cancer Group (SLCG) BRCA1-RAP80 Expression Customization (BREC) randomized phase III trial of customized chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients with wild-type epidermal growth factor receptor (EGFR) (NCT00617656/GECP-BREC) (ID 1157)

      10:40 - 10:50  |  Author(s): C. Camps

      • Abstract
      • Presentation
      • Slides

      Background
      RAP80, a component of the BRCA1 complex, influenced outcome both in p with low BRCA1 expression treated with cisplatin (cis)/gemcitabine (gem) and in p with intermediate/high BRCA1 levels treated with cis/docetaxel (doc) or with doc alone in the SLCG phase II customized chemotherapy trial (NCT00883480). Based on these findings, the SLCG and the French Lung Cancer Group performed a prospective, randomized phase III trial in metastatic NSCLC patients to compare non-customized cis/doc with customized therapy customized according to BRCA1 and RAP80 mRNA expression levels.

      Methods
      From 2008 to 2013, patients with wild-type EGFR were randomized 1:1 to the control or experimental arm. Planned accrual was 391 patients. Treatment in the control arm was cis/doc, while patients in the experimental arm received treatment according to their BRCA1 and RAP80 levels: 1) those with low RAP80, regardless of BRCA1 levels, received cis/gem; 2) those with intermediate/high RAP80 and low/intermediate BRCA1 received cis/doc; and 3) those with intermediate/high RAP80 and high BRCA1 received doc alone. The primary endpoint was progression-free survival (PFS).

      Results
      At 15 October 2012, 279 patients had been included and the planned interim analysis was performed. PFS was 5.49 months (m) in the control and 4.38 m in the experimental arm (P=0.07). Overall survival (OS) was 12.66 m in the control and 8.52 m in the experimental arm (P=0.006). Response rate (RR) was 37.3% in the control and 27% in the experimental arm (P=0.07). In the multivariate analysis including PS, treatment arm, BRCA1, RAP80, histology, smoking status and metastatic site, only extrathoracic metastases were associated with an increased risk of progression (HR, 1.78; P=0.02). In a post hoc analysis restricted to patients with ECOG PS 0, PFS was 3.91 m in the control and 7.47 m in the experimental arm (P=0.01) for those with low RAP80 levels (experimental group 1). PFS for patients in experimental groups 1, 2 and 3 was 7.47, 7.01 and 3.22 m, respectively (P=0.02). OS for patients in experimental groups 1, 2 and 3 was 28.88, 15.86 and 11.81 m, respectively (P=0.04).

      Conclusion
      Based on the negative results for PFS at the interim analysis, accrual was closed on this study. The negative results may be due to the poor predictive capacity of RAP80 and/or to the inclusion of doc alone as a treatment in the experimental arm. In addition, doc/cis may not have been the ideal combination for the control arm. Customized chemotherapy could be further encouraged in oncogene-driven pan-negative patients with PS 0.

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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.06-030 - KRAS mutations in resectable NSCLC patients. Prognostic implications. (ID 2273)

      09:30 - 09:30  |  Author(s): C. Camps

      • Abstract

      Background
      Development of Non-Small Cell Lung Cancer (NSCLC) requires multiple genetic and epigenetic alterations, with some differences according to etiology and histology. The most frequently mutated genes in these tumors are EGFR and KRAS (present mostly in adenocarcinomas), however, the prognostic value of KRAS mutations in NSCLC is still controversial.

      Methods
      Fresh tumor tissue samples (n=150) were obtained from resectable NSCLC patients. DNA was extracted by standard methods based in TriZol® and analyzed for KRAS mutational status by RTqPCR with ARMS technology and Scorpions probes. Non-parametric methods were used fos statistical analysis. Progression free survival (PFS) and overall survival (OS) were evaluated by Kaplan-Meier method (log-rank test). A p value ≤ 0.05 was considered statistically significant.

      Results
      Baseline characteristics of the patients were: median age, 64 years [26-82]; 86.0% male; 71.3% ECOG-PS 0; 40% adenocarcinomas (ADC). KRAS mutations were detected in 10.7% of the tumors (n= 150). Table 1 summarizes the mutations found in our cohort. In the subgroup of ADC + ADC-SCC samples, mutant KRAS represents 20% of the tumors. Considering only the never-smoker group of patients, 31.6% of the samples were mutated for KRAS. Our results showed that patients with KRAS mutated tumors had significantly shorter PFS than patients with wild type KRAS (11.633 vs 45.833 months, respectively, p= 0.043) and a trend to a shorter OS (23.067 vs 66.967 months, respectively, p= 0.074). Table 1: Distribution of KRAS mutations in our cohort

      n %
      Wild Type 134 89.3
      12SER 1 0.7
      12CYS 5 3.3
      12ASP 7 4.7
      12VAL 3 2.0
      TOTAL 150 100.0

      Conclusion
      KRAS gene mutation is a poor prognostic factor for PFS in our cohort of resectable NSCLC; therefore, the determination of the mutational status of KRAS gene might be implemented routinely in clinical practice. This work was supported in part, by a grant [RD06/0020/1024 and RD12/0036/0025] from Red Temática de Investigación Cooperativa en Cáncer, RTICC, and Instituto de Salud Carlos III (ISCIII).

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    P2.02 - Poster Session 2 - Novel Cancer Genes and Pathways (ID 148)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.02-013 - The importance of immunoregulatory genes in non small cell lung cancer (ID 2461)

      12:54 - 13:11  |  Author(s): C. Camps

      • Abstract

      Background
      In non small cell lung cancer (NSCLC) it is of vital importance to develop biomarkers that allow us to assign a more accurate prognosis for patients in early stages, so we can apply the right treatment at the right time, preventing that the cancer reaches advanced stages when the cure rate is close to zero.

      Methods
      In this study we have selected a set of 9 genes related to immunoregulation and inflammation processes to analyze their relative expression on mRNA by qPCR in lung tissue samples from patients with NSCLC and resectable stage. CCL2 and CD1c genes showed a significantly lower expression in tumor tissue versus healthy tissue. After that, we analyzed the correlation between expression levels of these genes and relevant clinicopathological variables in the patients. Poorly differentiated tumors showed higher expression levels of CD209, CCL2, LGALS1 and LGALS2, whereas in smokers an increased expression of galectin LGALS1 was documented. Finally, survival analysis was performed using the Kaplan-Meier method to assess the utility of genes as prognostic biomarkers in this disease.

      Results
      In the subgroup of patients with squamous cell histology, those with lower levels of expression of CCL22 showed a significant increase in overall survival (OS) and progression-free survival (PFS). In our cohort of patients with resectable NSCLC, survival analyses showed that elevated levels of galectin LGALS2 and CCL2 chemokine are associated with a better prognosis in overall survival (OS) and progression-free survival (PFS).

      Conclusion
      The data obtained in our study provide further evidence about the necessity of tumors to manipulate the microenvironment around them as a prelude to progress and invade tissues.

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    P3.06 - Poster Session 3 - Prognostic and Predictive Biomarkers (ID 178)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 2
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      P3.06-035 - Study of the correlations between SNPs in angiogenic genes and treatment response/ outcome in patients with advanced NSCLC (non-squamous histology) treated in first line with carboplatin, paclitaxel and bevacizumab (CPB). The ANGIOMET study. (ID 2664)

      09:30 - 09:30  |  Author(s): C. Camps

      • Abstract

      Background
      It has been demonstrated that the addition of bevacizumab to paclitaxel plus carboplatin (CPB) in the treatment of advanced NSCLC improves survival. Even though, there is a high variability in drug efficacy between patients, leading to different response rates. ANGIOMET is an exploratory study promoted by the SLCG in advanced NSCLC, non-squamous histologies (NS-NSCLC) treated in first line with a combination scheme based in CPB, designed to investigate the relationship between angiogenic mediators and the outcome and response to treatment. The primary end-point was progression-free survival (PFS), and the secondary end-points are the follows: OS, response-rates and toxicity profiles.

      Methods
      In this multicentric study, patients with stage IIIB/IV NS-NSCLC (ECOG status 0–2) were included and treated in first line with CPB. Peripheral blood samples were collected before treatment administration and DNA was purified from the leukocyte fraction. Ten SNPs of VEGF-pathway genes were genotyped in 186 samples by RT-PCR in duplicate. SNPs were related to PFS and OS (Kaplan-Meir method, log-rank test) and to response rate.

      Results
      10 SNPs were determined in 186 DNA samples. In this preliminary analysis there were data from 108 patients valid for PFS and OS analysis. Baseline characteristics of the patients were: median age, 63 years [37-80]; 74.5% male; 94.1% ECOG PS 0-1; 14% never-smokers, 100% caucasian; 89.7% adenocarcinomas, 2.8% large cell carcinomas; median number of CPB cycles was 4. There was no response assessment in 27 patients (25%), 30.6% PR, 31.5% SD and 13.0% PD. The SNP rs833061 (CC) in VEGFA correlated with lower response rates to CPB than the other genotypes (p=0.07). SNPs in KRAS and VEGFR2 were associated with PFS and/or OS in our cohort. The KRAS SNP rs10842513 (TT+CT) was associated with shorter PFS compared with the CC genotype (median: 5.39 vs 6.81 months; p=0.04, respectively). The VEGFR2 SNP rs2071559 (AA) was significantly associated with longer PFS and OS (Table 1). No significant differences in PFS or OS were observed according to other SNPs analyzed. Table 1: PFS and OS for VEGFR2 SNPrs2071559.

      PFS
      % Median (months) 95%CI p
      VEGFR2 (rs2071559)
      AA 25.6 9,408 5,084 - 13,732 0.01
      GG+AG 74.0 5,724 4,902 - 6,546
      OS
      % Median (months) 95%CI p
      VEGFR2 (rs2071559)
      AA 25.6 NR ---- 0.001
      GG+AG 74.0 12,270 8,760 – 15.780

      Conclusion
      These preliminary data indicate that genetic variation in VEGFR2, SNP rs2071559 variant AA, is associated with prognosis in advanced NS-NSCLC patients treated with CPB and may have predictive implications as biomarkers in patients treated with chemotherapy with bevacizumab. On behalf of the Spanish Lung Cancer Group (SLCG)

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      P3.06-037 - Expression of stemness factors OCT4 and NANOG in resectable non-small cell lung cancer. (ID 2695)

      09:30 - 09:30  |  Author(s): C. Camps

      • Abstract

      Background
      Epithelial–mesenchymal transition (EMT) and expression of stemness features are key issues for tissue invasion and metastasis during cancer development. OCT4 and NANOG are homebox transcription factors essential to the self-renewal of stem cells and are expressed in several cancers. The role of OCT4/NANOG signaling in tumorigenesis and as biomarkers in non-small cell lung cancer (NSCLC) is still elusive.

      Methods
      mRNA was isolated from 177 frozen samples, corresponding to tumoral and normal parenchyma of NSCLC patients in resectable-stage. OCT4 and NANOG relative expression was determined by RTqPCR using hydrolysis probes. Expression levels were normalized using GUSB as endogenous housekeeping gene. Statistical significance was considered for p<0.05.

      Results
      Patient’s median age was 64 years [26-87], 87.6 % were males, 75.2 % presented performance status (PS=0) and 47.3% had squamous histology. We found a significant positive correlation between OCT4 and NANOG expression (r[2 ]=0.61 p<0.0001, Pearson test). Higher levels of expression of NANOG were related to poor differentiation grade (p= 0.04). Survival analysis revealed that there is a trend to a poorer progression free survival in the subgroup of patients with higher levels (> median) of expression of OCT4 levels

      Conclusion
      The transcription factor OCT4 may have a role as prognostic biomarker in resectable NSCLC. (Supported in part by ISCIII (PI12/02838), RTICC (RD12/0036/0025), Ministry of Economy and Competitiveness and SEOM Grants 2012)