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D. Beer
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MS 26 - Genomic Alterations and Drug Targets in Small Cell Lung Cancer (ID 44)
- Event: WCLC 2015
- Type: Mini Symposium
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 5
- Moderators:D. Beer, J.W. Goldman
- Coordinates: 9/09/2015, 14:15 - 15:45, Mile High Ballroom 2c-3c
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MS26.01 - Genomic Alterations (ID 1963)
14:15 - 15:45 | Author(s): J.C. Yang
- Abstract
- Presentation
Abstract:
Genomic Alterations and Drug Targets in Small Cell Lung Cancer Over the past 15 years, we have made a lot of advances in the treatment of non small cell lung cancer (NSCLC). However, the treatment paradigm for small cell lung cancer (SCLC) remains the same as 30 years ago, e.g., concurrent chemoradiotherapy for limited stage SCLC and chemotherapy for extensive stage SCLC. The successful introduction of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for the treatment of lung cancer patients has helped us understand the underlying genomic alterations in responding patients and the biology of tumor cells harboring EGFR mutations. In contrast to the successful story of EGFR TKIs in NSCLC treatment leading to the discovery of EGFR mutations in responding patients, the discovery of EML4-ALK fusion in NSCLC has led to the successful treatment of crizotinib in patients harboring this mutation. Crizotinib was designed to inhibit cMET but was developed successfully as an ALK inhibitor for those patients. Further genomic analysis of lung adenocarcinoma patients disclosed that some specific recurrent mutations in EGFR, HER2, KRAS, NRAS, BRAF, cMET, EML4-ALK, ROS1, RET fusions etc. were found in patients. However, each patient only harbored one mutation. Specific inhibitors are very effective in the treatment of lung adenocarcinoma patients harboring corresponding targeted mutations. Thus, driver mutation or oncogene addiction hypothesis was built through genomic analysis of lung adenocarcinoma patients and clinical observations of successful targeted therapy treatment. Several targeted therapies have been tested in a small scale of advanced stage SCLC patients. None of the studies showed any signal of anticancer activity in years. Thus, radiotherapy and chemotherapy remain the effective treatment for SCLC. Current technique allowed us to examine cancer genome in detail. The information can be used to predict clinical usage of certain targeted therapy. Genomic analysis of SCLC may open a door for us to understand the basic differences between NSCLC and SCLC and ponder the ineffectiveness of targeted therapy in SCLC. Genomic alterations of SCLC cells were first described in 1980s by observation of chromosome aberrations. Frequent deletion of 3p was first observed by Peng-Whang J et al. The most frequent reported genetic alterations in SCLC cells were inactivting mutations of TP53, RB1, PTEN, mutations in PIK3CA, EGFR and KRAS, amplification of myc family, EGFR and BCL2 as well as loss of RASSF1A, PTEN and FHIT. Those genomic alterations were examined through small series of samples and target gene examinations. Systemic approach to explore the multitude and magnitude of genomic alterations in SCLC was only possible with recent next generation sequencing technology and the application of bioinformatics to analyze the vast amount of data generated from the samples. Rudin et al. have collected 36 primary human SCLC and normal tissue pairs and 17 matched SCLC and lymphoblastoid cell lines and examined the exome, transcriptome and copy number alterations. In 4 primary tumors and 23 SCLC cell lines, the authors identified 22 significant mutated genes. In the exome of 42 SCLC tumor normal tissue pairs, they identified 26406 somatic mutations. 30% of them resulted in protein alterations. An average of 175 protein-altering single nucleotide variants was calculated per patient. G-to-T transversions were the predominant mutation, followed by G-to-A and A-to-G transition mutations signify that these mutations were related to tobacco smoke carcinogens. In the whole genome analysis of one patient, 286 protein-altering changes were found. Frequent altered genes included genes encoding for kinases, G-protein-coupled receptors and chromatin-modifying proteins. The authors found that SOX2 mutation or amplification was frequently found in its series. SOX2 expression may play some crucial roles in SCLC cells, such as maintenance of pluripotency of stem cells property. In addition, the authors also discovered several non-recurrent fusion genes from RNA-seq data. The roles of these fusion proteins in SCLC are less well understood. But some of those fusion proteins seem to result in activating kinases. Peifer M et al. sequenced 29 SCLC exomes, 2 genomes and 15 transcriptomes. They discovered inactivation of TP53, RB1 and recurrent mutations in CREBBP, EP300 and MLL genes. Additional findings included mutations in PTEN, SLIT2, EPHA7 and FGFR1 amplification. They concluded that histone modification is a major feature of SCLC. Both comprehensive genomic studies disclosed similar gene alterations such as TP53 and RB1 are the important signatures of SCLC genomic alterations. However, an individual analysis pointed out at different angles, for example, SOX2 or histone modification. The different results of two series reflected that only a limited number of samples were tested, interpatient heterogeneity may be huge and more genomic studies should be performed in the future. When major genomic alterations were compared among lung adenocarcinoma, squamous cell carcinoma and SCLC, alterations of TP53, CDKN2A, PIK3CA and PTEN were commonly found in all three types of lung cancer. FGFR1 and SOX2 alterations were found in SCLC and squamous cell carcinoma, whereas KEAP1 alterations was detected in both squamous cell carcinoma and adenocarcinoma. Recently, transformation from adenocarcinoma to SCLC was detected in a minority of patients with EGFR mutations who have received EGFR TKIs and developed resistance. Typical EGFR mutations can be found in untreated SCLC patients, especially in east Asian ethnic patients. Occasionally mixed SCLC and adenocarcinoma were described under light microscopy. Some of those patients harbor EGFR mutations. Unfortunately, EGFR TKI was usually not effective in the treatment of such patients, it suggested that alterations of the transcriptional factors contributed SCLC phenotype being more dominant and only chemotherapy was effective to control the progression of the disease. The heterogeneous nature of genomic alterations in SCLC suggested that targeted therapy may be difficult to be successful in SCLC treatment. None of the altered genes seems to be the dominant driver. On the other hand, RB1 and myc, genes altered easily that are not the good targets for current targeted therapy. Thus, genomic analysis of SCLC further indicated that the combination of targeted therapy may not be useful. It may have to combine targeted therapy and chemotherapy to obtain better anti-cancer activity. However, patient selection may be needed according to the genomic findings and pathway predictions. The hyper mutational genomic background was a good predictor for immune checkpoint inhibitor therapy. However, in a recent report in American Society of Clinical Oncology Meeting suggested that only a low response rate was noted in SCLC treated with immune checkpoint inhibitors. More genomic, immune studies and clinical trials are needed to advance the treatment of SCLC in the future.
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MS26.02 - The MYC/MAX and the SWI/SNF Networks: Biological Understanding and Therapeutic Applications (ID 1964)
14:15 - 15:45 | Author(s): M. Sanchez-cespedes
- Abstract
- Presentation
Abstract:
The SWI/SNF chromatin-remodeling complex modifies the structure of the chromatin by the ATP-dependent disruption of DNA–histone interactions at the nucleosomes to activate or repress gene expression. The widespread occurrence of alterations at genes encoding different components of the SWI/SNF complex reveals an important new feature that sustains cancer development and offers novel potential strategies for cancer therapeutics. We discovered that in lung cancer the SWI/SNF component, BRG1 (also called SMARCA4), is genetically inactivated in about thirty per cent of non-small cell lung cancers (NSCLC), and that its inactivation occurs in a background of wild type MYC (either C, L or N). Here, we also report our discovery of tumor-specific inactivation of the MYC-associated factor X gene, MAX, in about ten percent of small cell lung cancers (SCLC). This is mutually exclusive with alterations at MYC and BRG1. We also demonstrate that BRG1 regulates the expression of MAX through direct recruitment to the MAX promoter, and that depletion of BRG1 strongly hinders cell growth, specifically in MAX-deficient cells, heralding a synthetic lethal interaction. Furthermore, MAX requires BRG1 to activate neuroendocrine transcriptional programs and to up-regulate MYC-targets, such as glycolytic-related genes. Finally, we observed genetic inactivation of the MAX dimerization protein, MGA, in lung cancers with wild type components of the SWI/SNF or MYC pathways. Our results provide evidence that an aberrant SWI/SNF-MYC network is essential for lung cancer development. Altogether, the genetic observations coupled with the functional evidence demonstrate that an aberrant SWI/SNF-MYC network is essential for lung cancer development, and opens novel therapeutic possibilities for the treatment of SCLC patients with MAX-deficient tumors. In healthy adults and during embryonic development, the complex is involved in the control of cell differentiation and in the specification of different tissues. The effect of the SWI/SNF complex on some of these processes is, at least in part, related to its involvement in regulating hormone-responsive promoters. Components of the SWI/SNF complex bind to various nuclear receptors, such as those of estrogen, progesterone, androgen, glucocorticoids and retinoic acid, thereby adapting the gene expression programs to the demands of the cell environmental requirements. Retinoic acid (RA) and glucorticoids (GC) are well known modulators of cell differentiation, embryonic development and morphogenesis. Their role in promoting cell differentiation makes it possible to use GC and RA therapeutically to treat some types of cancers. GC are part of the curative treatment of acute lymphoblastic leukemia while RA is the therapeutic agent for some neuroblastomas and acute promyelocytic leukemia, which both carry the PML–RARa gene fusion. GC are also used as a co-medication in the therapy of solid tumors, because of their effectiveness in treating the malignancy, or due to their less severe side effects in cancer treatment, such as electrolyte imbalance, nausea and emesis. However, most solid tumors, including lung cancers, are refractory to GC- and RA-based therapies. Underlying some cases of refractoriness to GC and RA is a dysfunctional SWI/SNF complex, for example due to alterations at BRG1. On the other hand, compounds that modulate the structure of the chromatin are currently used to treat cancer. These include histone deacetylase (HDAC) inhibitors, in hematological malignancies and cutaneous T-cell lymphomas, and inhibitors of DNA methylation such as azacytidine for myelodysplasic syndrome. HDACs and DNA methylation inhibitors promote gene transcription by increasing DNA accessibility through the inhibition of histone deacetylation and DNA methylation, respectively. These drugs have been tested in lung cancer patients in two studies, in which they showed no major responses. However, in a phase I/II trial, the combination of the two inhibitors produced a median survival of the entire cohort that was significantly longer than those of the existing therapeutic options. Here, we aimed to determine whether there could be a therapeutic use for GC plus RA (GC/RA) in combination with the epigenetic drugs azacytidine and SAHA (A/S) for treating lung cancers carrying BRG1 inactivation or MYC amplification. We found that in vitro, GC/RA treatment reduced growth, triggered pro-differentiation gene expression signatures and downregulated MYC, in MYC-amplified but not in most BRG1-mutant lung cancer cells. The co-administration of A/S enhanced all these effects, accompanied by sustained reductions in genome-wide DNA methylation. In vivo, treatments with GC/RA improved overall survival of mice implanted with MYC-amplified cells and reduced tumor-cell viability and cell proliferation. Thus, we propose that the combination of retinoids, corticoids and epigenetic treatments of lung tumors with MYC amplification constitute a strategy for therapeutic intervention in this otherwise incurable disease. REFERENCES Collins SJ. The role of retinoids and retinoic acid receptors in normal hematopoiesis. Leukemia 2002; 16, 1896–905. Liu SV, Fabbri M, Gitlitz BJ, Laird-Offringa IA. Epigenetic therapy in lung cancer. Front Oncol 2013; 3, 135. Medina PP et al. Frequent BRG1/SMARCA4-inactivating mutations in human lung cancer cell lines. Hum Mut 2008; 29, 617-22a. Pottier N et al. The SWI/SNF chromatin-remodeling complex and glucocorticoid resistance in acute lymphoblastic leukemia. J Natl Cancer Inst 2008; 100, 1792-803. Rodriguez-Nieto S et al. Massive parallel DNA pyrosequencing analysis of the tumor suppressor BRG1/SMARCA4 in lung primary tumors. Hum Mut 2011; 32, E1999-2017. Romero OA et al. The tumour suppressor and chromatin-remodelling factor BRG1 antagonizes Myc activity and promotes cell differentiation in human cancer. EMBO Mol Med 2012; 4, 603-16. Romero OA et al. MAX inactivation in small cell lung cancer disrupts MYC-SWI/SNF programs and is synthetic lethal with BRG1. Cancer Discov 2014; 4, 292-303. Romero OA, Sanchez-Cespedes M. The SWI/SNF genetic blockade: effects in cell differentiation, cancer and developmental diseases. Oncogene 2014; 33, 2681-9. Rutz HP. Effects of corticosteroid use on treatment of solid tumours. Lancet 2002; 360, 1969–70. Wilson GB,Roberts CWM. SWI/SNF nucleosome remodellers and cancer. Nat Rev Cancer 2011; 11, 481-92.
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MS26.03 - Targeting ASCL1 in Neuroendocrine Lung Cancers via a MAPK-Regulated Double-Negative Feedback Loop (ID 1965)
14:15 - 15:45 | Author(s): J. Minna, A. Augustyn, S. Earnest, P. Dospoy, J. Johnson, M. Cobb
- Abstract
- Presentation
Abstract:
ASCL1 is a lineage-specific transcription factor responsible during development for the formation of pulmonary neuroendocrine cells. ASCL1 is highly expressed in the majority of neuroendocrine lung tumors including small cell lung cancer (SCLC) and non-small cell lung cancer with neuroendocrine features (NSCLC-NE). Others have shown that SCLC survival depends on continued ASCL1 expression while we showed that ASCL1 is also required for the survival of NSCLC-NEs; that ASCL1 down-stream targets predict for poor survival in NSCLC patients; and that BCL2 is a therapeutically actionable ASCL1 target gene (PNAS 2014;111(41):14788-93). Thus, we are trying to target ASCL1 and its “druggable” downstream genes by developing ASCL1 based ChIP-Seq datasets in SCLC and NSCLC-NE tumors. We have now discovered a way to reliably regulate ASCL1 protein expression through “upstream” targeting. Phorbol 12-myristate 13-acetate (PMA) is an agonist of the MAPK pathway via specific activation of Protein Kinase C. Treatment of ASCL1(+) HCC1833 cells for 24 hours with nM quantities of PMA resulted in a robust down-regulation of ASCL1 mRNA and protein. Tumor cell death was apparent and apoptosis confirmed via induction of cleaved PARP. ASCL1 down-regulation was associated with activation of the MAPK pathway, measured by increased protein levels of phosphorylated ERK (pERK), and decreased ASCL1 mRNA expression was found to be at least partly due to mRNA degradation. These data indicate that activation of the MAPK pathway in high-grade neuroendocrine tumors has potential for therapeutic intervention and also provides a reason for the previously unexplained low levels of MAPK activation (pERK) in SCLC. Unexpectedly, we also found that siRNA mediated knockdown of ASCL1 resulted in activation of the MAPK pathway. In addition, pERK was significantly induced with ASCL1 knockdown even when we also knocked down MEK1 (MEK1 knockdown by itself completely eliminated pERK expression). The MAPK pathway depends on active phosphorylation/dephosphorylation and this is regulated in part by dual-specificity phosphatases (DUSPs). Using our ASCL1 ChIP-Seq data, we identified a conserved ASCL1 binding site in the promoter region of DUSP6. DUSP6 mRNA was found to be dramatically elevated in ASCL1(+) lines HCC1833 and H889, while by contrast there was little or no DUSP6 expression in ASCL1(-) SCLC lines H82 and H526, and knockdown of ASCL1 resulted in a decrease of DUSP6 protein suggesting transcriptional regulation. This led us to try a DUSP6 allosteric inhibitor (E/Z-BCI, Sigma-Aldrich) which induced pERK, decreased ASCL1 protein expression, and inhibited soft agar colony forming ability of H889 SCLC cells. In conclusion: Our data indicate that the MAPK pathway regulates ASCL1 expression, where activation of pERK signaling is correlated with decreased ASCL1 mRNA and protein. In addition, ASCL1 in turn, actively down-regulates the MAPK pathway. Our hypothesis is that high-grade neuroendocrine lung cancers down-regulate the MAPK pathway in order to maintain ASCL1 expression, which promotes cell survival and maintenance of the neuroendocrine lineage. This points to a double-negative feedback loop involving the MAPK pathway, ASCL1, and at least one DUSP. Targeting components of the MAPK pathway regulating ASCL1 expression is thus a new therapeutic avenue for high-grade neuroendocrine lung cancers. (Lung Cancer SPORE P50CA70907, NIH 1F30CA168264, CPRIT).
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MS26.04 - FGFR1 Co-Activation Networks in Lung Cancer (ID 1966)
14:15 - 15:45 | Author(s): L. Heasley
- Abstract
- Presentation
Abstract:
FGFR1 is a therapeutic target under investigation in multiple solid tumors and clinical trials of FGFR-specific and selective tyrosine kinase inhibitors (TKIs) are underway. Our recent studies have demonstrated a role for unmutated FGFR1 as a driver in lung cancer cell lines of all histologies including small cell lung cancers (SCLCs), head and neck squamous cell carcinomas (HNSCCs) and mesotheliomas. Although potent in vitro growth suppression of lung cancer cell lines is observed in response to multikinase inhibitors such as ponatinib as well as FGFR-specific TKIs (AZD4547, BGJ398), the in vivo inhibitory effects of these drugs on xenografts propagated in immune deficient mice are more modest and short-lived in our hands. Thus, while treatment with single FGFR TKIs represents a logical entry point to personalized therapy of cancers bearing over-expressed FGFR1, we hypothesize that intrinsic mechanisms involving rapid kinome reprogramming events limit the therapeutic efficacy of these TKIs. In fact, ample precedent exists to support the signaling of receptor tyrosine kinases (RTKs) within "co-activation networks" where multiple RTKs engage multiple signal pathways to bring about robust and flexible activation of signal cascades. We deployed RNAi-based functional genomic screens to identify protein kinases controlling the intrinsic sensitivity of FGFR1-dependent lung cancer and HNSCC cells to ponatinib, a multi-kinase FGFR-active inhibitor. Mammalian Target of Rapamycin (MTOR) was identified and validated as a synthetic lethal kinase with ponatinib in H157 and H1299 cells. In other FGFR1-expressing cell lines (Colo699, H520 and H1703), MTOR was an essential protein kinase as evidenced by high sensitivity to MTOR-targeting shRNAs and pharmacological inhibitors. Despite wide ranging MTOR dependencies observed among the FGFR1-dependent cell lines, synergistic in vitro growth inhibition was a general observation when FGFR inhibitors where combined with pharmacological inhibitors of MTOR or AKT. At the molecular levels, FGFR inhibitors potently inhibited MEK/ERK activity while MTOR inhibitors reduced the activity of TORC1 (p70S6K, S6) and TORC2 (AKT Ser473)-specific targets. In combination, FGFR TKIs and MTOR inhibitors simultaneously eliminated MEK/ERK and MTOR signaling. Xenografts generated from the FGFR1-dependent lung cancer cell lines, Colo699 and H1581, exhibited only modest sensitivity to monotherapy with the FGFR-specific TKI, AZD4547. However, consistent with the in vitro findings, combination treatment with AZD4547 and the MTOR inhibitor, AZD2014, afforded significantly greater tumor growth inhibition and prolonged survival. The data support the existence of a signaling network wherein unmutated FGFR1 drives the ERK pathway and distinct receptors under investigation activate the MTOR/AKT pathway to induce full transformation. Combining MTOR inhibitors with FGFR-specific TKIs may yield greater clinical efficacy in FGFR1-driven lung cancers.
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MS26.05 - Drug Screening Targets (ID 1967)
14:15 - 15:45 | Author(s): C. Lee Hann
- Abstract
- Presentation
Abstract not provided
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Author of
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MINI 12 - Biomarkers and Lung Nodule Management (ID 109)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:J.M. Siegfried, H.I. Pass
- Coordinates: 9/07/2015, 16:45 - 18:15, 401-404
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MINI12.01 - A Novel Serum 4-MicroRNA Signature for Lung Cancer Detection (ID 585)
16:45 - 18:15 | Author(s): D. Beer
- Abstract
- Presentation
Background:
Early detection of lung cancer using low-dose CT led to a 20% reduction in mortality. However, this strategy has several limitations including high false-positive rates, potential over-diagnosis, and the potential harm associated with radiation exposure. The aim of this study was to identify differentially-expressed miRNAs in the serum of non-small cell lung cancer (NSCLC) patients that might be a clinically-useful tool for lung cancer early detection.
Methods:
We performed miRNA expression profile analysis using TaqMan OpenArray Human panel in a discovery set of 70 serum samples obtained at lung tumor resection including lung adenocarcinoma (AD) and lung squamous carcinoma (SCC) and 22 non-cancer subjects (NC). To construct the diagnostic signature, the miRNA candidates were selected based upon the following criteria: miRNAs significantly up-regulated (adjusted t-test p < 0.001) in the NSCLC tissue and serum as compared to normal lung tissue and NC serum respectively, not overexpressed in circulating blood cells and with Area Under the Curve (AUC) > 0.840 for discriminating stage I LC from NC in the receiver-operating characteristic (ROC) plots. Selected serum miRNAs were then validated by quantitative PCR using an independent validation set of serum samples from LC patients (n=84) and NC (n=23).
Results:
Sixty miRNAs were significantly up-regulated and 31 were down-regulated in the serum from NSCLC patients versus NC (adjusted p<0.001). Four miRNAs (miR-193b, miR-301, miR-141 and miR-200b) were selected for validating their diagnostic value in an independent cohort. A diagnostic signature was obtained by logistic regression based upon the expression values of these 4 serum miRNAs in the discovery set. This miRNA signature generated an AUC of 0.985 (95% CI 0.961 – 1.000, p < 0.001) for detecting NSCLC (all stages) and of 0.989 (95% CI 0.967 – 1.000, p < 0.001) for detecting stage I NSCLC in the discovery set. In the test set, the diagnostic utility of this miRNA signature was validated and exhibited an AUC of 0.993 (95% CI 0.979 – 1.000, p < 0.001).
Conclusion:
We identified a serum 4-miRNA signature that discriminated with high accuracy lung cancer patients from NC. Further prospective validation of this miRNA signature is warranted using an independent cohort of serum samples from patients who participated in a lung cancer screening program.
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MINI 34 - RNA and miRNA (ID 162)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 2
- Moderators:C. Mascaux, L.(. Wang
- Coordinates: 9/09/2015, 18:30 - 20:00, 205+207
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MINI34.03 - Novel microRNA Prognostic Signature in Malignant Pleural Mesothelioma (ID 2988)
18:30 - 20:00 | Author(s): D. Beer
- Abstract
- Presentation
Background:
Malignant pleural mesothelioma (MPM) is an aggressive tumor mainly associated with asbestos exposure. MPM patients have a poor outcome (median overall survival (mOS) <1 year), therefore novel therapeutic approaches are needed. MiRNA have been demonstrated to have a role in tumorigenesis and progression in MPM. This study aimed to identify a miRNA signature associated with poor prognosis.
Methods:
We identified 26 un-resected MPM patients split as follows: 11 long survivors (LS) OS>3 years and 15 short survivors (SS) OS<1 year. MiRNA expression in 26 FFPE biopsy and 3 normal pleura (NP) was evaluated using Agilent Human miRNA Microarray platform including 2006 miRNA. Expression data were normalized by GeneSpring software (v.12.6). Class-comparison analysis between MPM/NP and SS/LS was performed using a t-test adjusted for multiple comparisons using Benjamini-Hochberg. OS curves were estimated using the Kaplan-Meier method and compared with the log-rank test. In silico validation was performed using miRseq data from TCGA portal based upon 16 patients (LS: 8; SS: 8). Candidate miRNA were assessed by univariate analysis using Kaplan-Meier method and median as cutoff.
Results:
Patients’ characteristics: median age 67 years (53-77); 81% males, 19% females; 73% epithelioid histotype, 12% sarcomatoid, 12% biphasic and 1 unspecified MPM. No differences in age, gender and histotype were observed between LS and SS. By class-comparison analysis, 30 miRNAs were significantly up-regulated and 11 down-regulated in MPM vs NP (adjusted p-value <0.05). Fourteen miRNAs were significantly associated with outcome, in the univariate survival analysis and differentially expressed in MPM. A miRNA signature, based on the top 6 prognostic miRNAs (unfavorable, miR-1224; favorable, miR-99a, miR-125b, let-7b, let-7c and let-7i) classified patients into low- or high-risk. High-risk patients showed a significantly shorter median OS (4.1 months, 95% CI 2.2-5.9) as compared with low-risk patients (median not reached, Log-rank p<0.001). In silico validation analysis confirmed that low expression of mir-99a, miR-125b and let-7c was associated with shorter OS. Relevant pathways, such as PI3K/AKT, WNT were associated with these top miRNAs by pathway analysis.
Conclusion:
A prognostic miRNA signature was identified by profiling a cohort of un-resected MPM, underlying the clinical potential of miRNA as predictors of survival. An additional validation in a larger independent cohort of MPM is ongoing.
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MINI34.15 - Discussant for MINI34.11, MINI34.12, MINI34.13, MINI34.14 (ID 3435)
18:30 - 20:00 | Author(s): D. Beer
- Abstract
- Presentation
Abstract not provided
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