Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
TRANSLATIONAL RESEARCH & BIOMARKERS –
MONDAY, DECEMBER 5, 2016
P1.05-021 CIRCRNAS: POTENTIAL NOVEL BIOMARKERS FOR THE
EARLY DETECTION OF LUNG CANCER
Ruby Lin 1 , Glen Reid 2 , Luciano Mutti 3 , Anthony Ryan 4 , Siobhan Nicholson 5 ,
Niamh Leonard 5 , Vincent Young 6 , Ronan Ryan 6 , Stephen Finn 7 , Sinead Cuffe 8 ,
Steven Gray 9
1 University of Sydney, Concord/ACT/Australia, 2 Asbestos Diseases Research
Institute, Sydney/Australia, 3 School of Environment & Life Sciences, University of
Salford, Salford/United Kingdom, 4 Dept. of Clinical Medicine, Trinity Translational
Medicine Institute (Ttmi), Dublin/Ireland, 5 Histopathology, Labmed Directorate,
Dublin/Ireland, 6 Cardio-Thoracic Surgery, Sacc Directorate, Dublin/Ireland, 7 Dept.
of Histopathology and Morbid Anatomy, Trinity College Dublin, Dublin/Ireland,
8 Oncology, Hope Directorate, Dublin/Ireland, 9 Thoracic Oncology Research Group,
Labmed Directorate, Dublin/Ireland
Background: Lung cancer is the leading cancer killer globally. Cancers such as
colon, breast, and prostate all have relatively reliable early detection tests.
In contrast, lung cancer does not. If caught early, lung cancer has a much
better prognosis. Non-invasive or minimally invasive tools to improve early
detection of lung cancer represents a critical unmet need. Analysis of the
human transcriptome indicates that a mere 2% of the genome corresponds
to protein coding transcripts, yet ~ 75% of the genome is transcribed. It is
now well established that these non-coding RNAs (ncRNAs) play important
regulatory functions within the cell and their expression are often altered in
cancer. Circular RNAs (circRNAs) are a species of ncRNAs. They are abundant,
conserved and demonstrate cell-type specific expression patterns. Moreover,
they are extremely stable with half-life’s greater than 48 hours, are resistant
to degradation by RNA exonucleases, and have been shown to play important
roles in cancer. Taken together these suggest that circRNAs could potentially
be important biomarkers in early lung cancer diagnosis. Methods: Total RNAs
isolated from a panel of matched normal/tumour NSCLC adenocarcinoma
(Stage IA/IB) samples (n=6) were probed for circRNAs using the Arraystar
circRNA microarray. Survival was assessed on linear mRNAs with associated
circRNAs using KM-Plot. Results: Interim analysis of the data has identified
n=206 circRNAs with a 2-fold difference in expression between their
matched normal vs. tumour counterparts. Principal Component Analysis
(PCA) demonstrated a clear separation of the samples (Tumour vs. Normal).
Self-Organizing Maps (SOMs) analysis generated distinctive SOMS clusters
of circRNAs, while associated linear pathway enrichment for microRNA
and transcriptional binding motifs identified several additional potential
networks. Moreover, an analysis of linear mRNAs associated with 10 circRNAs
with altered expression in adenocarcinomas found that these mRNAs were
linked to overall survival, and that the majority were adenocarcinoma specific.
Conclusion: Altered levels of a number of circRNAs were associated with lung
adenocarcinoma. A separate cohort of squamous cell carcinomas is currently
being assessed for circRNAs. At present we are validating the expression of
these circRNAs in a larger cohort of specimens, and assessing whether or not
these are detectable in plasma/serum from the same individuals. Overall,
circRNAs may represent novel potential biomarkers for the detection of
NSCLC, and may provide additional critical basic knowledge regarding the
development and biology of NSCLC.
Keywords: circRNA, biomarker, Early Detection
POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
TRANSLATIONAL RESEARCH & BIOMARKERS –
MONDAY, DECEMBER 5, 2016
P1.05-022 CIRCULATING TUMOR CELL ISOLATION TO MONITOR
NSCLC PATIENTS OVER THE COURSE OF TREATMENT
Julia Herrmann 1 , Jens Pfannkuche 2 , Thomas Lesser 1
1 Srh Wald-Klinikum Gera, Gera/Germany, 2 Gilupi GmbH, Potsdam/Germany
Background: Compared to the investigation of the primary tumor or a biopsy
taken from a distant metastasis, the investigation of a patient’s blood is
relatively simple, less invasive and can be performed repeatedly. Thus, CTC
(circulating tumor cells) investigation can be used as a real-time marker for
staging, disease progression and therapy responsiveness. Cancer mortality
might be reduced dramatically when the disease and its metastatic spread
are detected and characterized early and can therefore be treated in an
optimal fashion. The GILUPI CellCollector ® offers medical personnel at any
point-of-care with the unique opportunity to enrich these CTCs in vivo.
Here, we conducted a study using this effective device, to monitor CTC
counts before as well as on different time points after surgery in non-small
cell lung cancer (NSCLC) patients and further to characterize the CTCs on a
molecular level. Methods: In total, 20 NSCLC patients (different stages) were
screened for CTCs at different time points: preoperative, 30 minutes after
tumor resection, 1 week postoperative as well as in 3-monthly intervals up
to 2 years. In addition, 1 patient with a benign lung disease were included
in this study. Results: CTCs were isolated independent from tumor stages
and even in quite early cases CTCs could be detected. Moreover, a difference
between CTC occurrence before and after surgery was seen and a correlation
between CTC enumeration and clinical lack of recurrence could be detected.
Conclusion: The GILUPI CellCollector® overcomes blood volume limitations of
other diagnostic approaches and thereby increases the diagnostic sensitivity
of CTC analysis. Future implementation into clinical practice may improve
early detection, prognosis and therapy monitoring of cancer patients. Besides
enumeration, captured CTCs are ready for molecular characterization and will
help to establish more personalized treatment regiments since knowledge of
the molecular make-up of the cancer cells to be defeated is an indispensable
prerequisite to use targeted therapies efficiently.
POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
TRANSLATIONAL RESEARCH & BIOMARKERS –
MONDAY, DECEMBER 5, 2016
P1.05-023 INDUCTION OF PATIENT-DERIVED XENOGRAFT
FORMATION AND CLINICAL SIGNIFICANCE FOR PD-L1 IN LUNG
CANCER PATIENTS
Panpan Zhang, Yuanyuan Ma, Jiahui Si
Department of Thoracic Surgery Ii, Peking University Cancer Hospital & Institute,
Beijing/China
Background: The relevance of programmed cell death ligand 1 (PD-L1)
to patient-derived xenograft (PDX) formation and clinicopathological
characteristics in early stage lung cancer was studied Methods: Cell counting
kit-8 and flow cytometry were carried out to examine proliferation and
apoptosis in PC9 and H520 cells transfected with siRNAs. Nod-scid mice were
used to establish PDX. Immunohistochemistry was done to investigate PD-L1
expression in tumor tissues. Results: Proliferation was reduced and apoptosis
was induced when PD-L1 was inhibited in the cells. Higher PD-L1 expression
rate was observed in the primary tumors with PDX formation than in the
tumors without PDX formation. Moreover, PD-L1 was found to be related to
smoking, histological types, stages and overall survival in 209 of lung cancer
patients. Conclusion: This study suggests that PD-L1 promotes PDX formation
ability and is an independent prognostic marker for the early stage lung
cancer patients.
Keywords: PD-L1, Patient-derived xenograft, lung cancer, clinical significance
POSTER SESSION 1 - P1.05: EARLY STAGE NSCLC
TRANSLATIONAL RESEARCH & BIOMARKERS –
MONDAY, DECEMBER 5, 2016
P1.05-024 PREOPERATIVE NEURON-SPECIFIC ENOLASE TO
ALBUMIN RATIO IS A PROGNOSTIC BIOMARKER FOR PATIENTS
WITH OPERABLE NON-SMALL-CELL LUNG CANCER
Hong Ren 1 , Xiang Li 2 , Boxiang Zhang 1 , Yiwen Zhang 1 , Litao Yang 1 , Guodong
Xiao 1 , Xiao Gao 1 , Guanghong Huang 1 , Peili Wang 1 , Huangzhen Wang 1 ,
Chengcheng Yang 1 , Sida Qin 1
1 Department Two of Thoracic Surgery, The First Affiliated Hospital of Xi’An Jiaotong
University, Xi’An/China, 2 The First Affiliated Hospital of Xi’An Jiaotong University,
Xi’An/China
Background: Neuron-specific Enolase (NSE) is a widely used tumor biomarker
in small-cell lung cancer (SCLC) diagnosis, and serum albumin (Alb) levels are
commonly used as indicators of the nutritional status of cancer patients.
However, the prognostic value of these markers in combination has not been
examined. This study was designed to explore the value of the combination
between NSE and Alb in non-small-cell lung cancer (NSCLC). Methods: We
retrospectively evaluated the prognostic value of the preoperative NSE
to albumin ratio (NAR) in 319 patients with operable NSCLC. We analyzed
associations among the NAR, clinicopathological characteristics, and
inflammatory biomarkers. Univariate and multivariate analyses were
performed to identify the clinicopathological characteristics associated
with OS. Furthermore, we compared the prognostic value of the NAR with
other established prognostic indexes by evaluating the area under the curves
(AUC). Results: The optimal NAR cutoff level was found to be 3.2×10 -7 . We
found that a higher NAR was associated with more advanced TNM staged
cancers (P=0.041) and higher tumor stage (P=0.011).The NAR was also
associated with the inflammatory biomarker albumin/globulin ratio (AGR,
P=0.032), but not the neutrophil/lymphocyte ratio (NLR, P=0.295) or platelet/
lymphocyte ratio (PLR, P=0.260). In multivariate analyses, the NAR was an
independent prognostic factor for NSCLC patients (P