Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
patients. Conclusion: STMN1 expression was an independent prognostic
factor for NSCLC, even when restricted to early stage patients.
POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY
PROTEINS IN LUNG CANCER AND PROTEOMICS –
TUESDAY, DECEMBER 6, 2016
P2.01-031 CCL CHEMOKINES MAY PLAY AN IMPORTANT ROLE IN
CISPLATIN RESISTANCE
Sarah-Louise Ryan 1 , Peter Godwin 2 , Susan Heavey 2 , Kazuo Umezawa 3 , Martin
Barr 2 , Steven Gray 2 , Bryan Stanfill 4 , Anthony Davies 1 , Sinead Cuffe 5 , Stephen
Finn 6 , Derek Richard 7 , Kathy Gately 2 , Kenneth O’Byrne 8 , Anne-Marie Baird 9
1 Translational Cell Imaging Queensland, Queensland University of Technology,
Brisbane/QLD/Australia, 2 Thoracic Oncology Research Group, Trinity College
Dublin/st. James’ Hospital, Dublin/Ireland, 3 Dept. of Molecular Target Medicine
Screening, Aichi Medical University, Aichi/Japan, 4 Csiro, Brisbane/ACT/Australia,
5 Dept of Medical Oncology, St James’ Hospital, Dublin/Ireland, 6 Dept of
Histopathology, St James’ Hospital, Dublin/Ireland, 7 Cancer Ageing and Research
Program, Queensland University of Technology, Brisbane/Australia, 8 Cancer and
Ageing Research Program, Princess Alexandra Hospital and Queensland University
of Technology, Brisbane/Australia, 9 St. James’ Hospital & Queensland University of
Technology, Dublin/Ireland
Background: In the absence of a targetable mutation, cisplatin based
chemotherapy is the backbone of NSCLC treatment. However, a diverse
patient population combined with complex tumour heterogeneity is
hampering its’ clinical utility. Although intrinsic and acquired resistance to
cisplatin is common, the mechanisms have not yet been fully elucidated.
However, some studies have suggested that inflammatory pathways may
play a key role in chemo-resistance. The aim of this project is to increase our
understanding of inflammatory mediated cisplatin resistance in NSCLC.
Methods: A number of isogenic cell line models of NSCLC (adenocarcinoma,
squamous cell carcinoma, large cell carcinoma) cisplatin resistance were
utilised to assess the role of inflammation in chemo-resistance. These
included a sensitive parental cell line (PT) and a matched resistant subtype
(CisR). The cell lines were screened for NFKB and a number of inflammatory
mediators including chemokines and TLRs at the mRNA (RT-PCR/qPCR)
and protein level (Western Blot/ELISA). A specific NFKB inhibitor, DHMEQ,
and recombinant chemokines were employed to further characterise
inflammatory pathways in PT and CisR cells in terms of cisplatin sensitivity,
proliferation (BrdU ELISA), cellular viability (Cytell Cell Imaging System) and
DNA damage response (Comet). An in vivo study was also completed using
DHMEQ alone and in combination with cisplatin. Results: A number of NFKB
targets and responsive pathways are deregulated in CisR cells compared
with their matched sensitive PT cell line. Amongst others, CCL2 and CCL5
were altered across all NSCLC subtypes. Preliminary data suggests that
DHMEQ enhances cisplatin sensitivity in both PT and CisR cells, conversely
recombinant chemokines elicit a protective effect. Additionally, DHMEQ
treatment resulted in opposite affects on CCL2 and CCL5 mRNA levels in
the PT and CisR cell lines. This may reflect an alternative pathway hierarchy
within the cells. Further characterisation is ongoing assessing chemokine
specific inhibitors. Although, in vivo data suggests a trend of decreased
tumour growth in the DHMEQ cohorts compared with vehicle control, the
data was not significant. However, tumour samples appeared more necrotic
with DHMEQ and are currently being characterised using IHC for necrosis and
proliferation. Conclusion: Targeting chemokines downstream of NFKB may
provide a means to overcome inflammatory mediated acquired and intrinsic
NSCLC chemo-resistance. Given the increased significance of immunooncology
agents to harness the body’s own immune system in the fight
against cancer, these agents may also prove fruitful in re-sensitising patients
to chemotherapy.
Keywords: non-small cell lung cancer, inflammation, Chemokines, Cisplatin
resistance
POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY
PROTEINS IN LUNG CANCER AND PROTEOMICS –
TUESDAY, DECEMBER 6, 2016
P2.01-032 IMPACT OF PREOPERATIVE SERUM ANTI-60S
RIBOSOMAL PROTEIN L29 LEVELS ON PROGNOSIS IN PATIENTS
WHO UNDERWENT SURGERY FOR NON-SMALL CELL LUNG CANCER
Hiromasa Yamamoto 1 , Akinobu Takaki 2 , Tatsuro Hayashi 3 , Masashi
Furukawa 3 , Hiroyuki Tao 3 , Kazuhiko Shien 1 , Junichi Soh 1 , Kazunori Okabe 3 ,
Shinichiro Miyoshi 1 , Shinichi Toyooka 1
1 Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate
School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama/Japan,
2 Gastroenterology and Hepatology, Okayama University Graduate School of
Medicine, Dentistry and Pharmaceutical Sciences, Okayama/Japan, 3 Thoracic
Surgery, Yamaguchi-Ube Medical Center, Ube/Japan
Background: Ribosome is a subcellular organelle, which serves as the site
of biological protein synthesis. Ribosomal protein L29 (RPL29) is one of
the proteins composing ribosome, and it expresses in cell surface as well
as in cytoplasm, especially showing its high expression in cancer cells.
Methods: We retrospectively reviewed 92 patients who underwent surgical
resection for non-small cell lung cancer between June 2010 and January
2012. Preoperative serum anti-RPL29 levels were measured by the indirect
enzyme-linked immunosorbent assay. The cut-off value was represented by
the median of anti-RPL29 levels. Results: The patients consisted of 60 males
and 32 females, and their average age was 68.7 years (range: 44-87 years).
Adenocarcinoma was the most common subtype (n = 69), which was followed
by squamous cell carcinoma (n = 13), adenosquamous cell carcinoma (n = 4),
pleomorphic carcinoma (n =4), and large cell carcinoma (n = 2). Postoperative
pathological stage consisted of stage IA (n = 28), IB (n = 28), IIA (n = 11), IIB (n
= 2), and IIIA (n = 23). EGFR activating mutations were found in 35 patients
(32 adenocarcinomas, 2 adenosquamous cell carcinomas, and 1 pleomorphic
carcinoma). The median of anti-RPL29 levels in 92 cases was 0.351. Threeyear
and five-year overall survival rate was 62.7% and 56.6%, respectively,
in the patients whose serum anti-RPL29 level was less than the median, and
90.0% and 83.7%, respectively, in the patients with the median or more of
anti-RPL29 levels (P = 0.005). In the multivariate Cox proportional hazard
model, anti-RPL29 level being the median or more and pathological stage IA
were identified as independent prognostic factors (P = 0.013 and P = 0.017,
respectively). Conclusion: Serum anti-RPL29 levels may be a novel prognostic
marker for non-small cell lung cancer.
Keywords: non-small cell lung cancer, serum, anti-RPL29, Prognosis
POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY
PROTEINS IN LUNG CANCER AND PROTEOMICS –
TUESDAY, DECEMBER 6, 2016
P2.01-033 EXOSOMAL PROTEOMICS ANALYSIS REVEAL NEW
TARGETS FOR RADIATION-INDUCED LUNG TOXICITY DIAGNOSIS
Xiance Jin, Congying Xie
Radiotherapy and Chemotherapy, The 1St Affiliated Hospital of Wenzhou Medical
University, Wenzhou/China
Background: radiation-induced lung toxicity (RILT) are observed today in
patients who have undergone thoracic irradiation for the treatment of lung
malignancy. Radiation-induced damage to normal lung parenchyma remains
the dose-limiting factor in chest radiotherapy. However, the radiative dosage
is not effective for most of patients because of avoiding RILT. Therefore, novel
diagnosis methods reveal individual potential RILT are required. For now,
increasing evidence illustrates that exosomes in circulating fluids provide a
promising way as biomarkers for noninvasive disease diagnosis. Exosomes
are 30–150 nm particles which are released from cells into the extracellular
environment and thousands of proteins have been identified in plasma
exosomes. Whether exosomal proteomics analysis could benefit lung cancer
patients with appropriate radiative dosage and prevent RILT remains to be
studied. Methods: Plasma samples were collected from RILT patients with
grade I and II, and no RILT individuals matched with age, gender and blood
collection time after 10 to 30Gy radiation within 6 months. Plasma exosomes
were accessed by 110,000×g ultracentrifugation and visualized by NS300
equipment. The raw data of exosomal proteomics profiles of RILT patients and
no-RILT individuals were generated by LC-MS and its expression were verified
by western blot. Results: In the present study, we revealed 17 exosomal
protein participated in wounding response and two of them were correlated
with RILT clinic stage. A2M (Alpha-2-macroglobulin) was decreased in RILT
patients and FGB (Fibrinogen beta chain) was increased in RILT patients.
Furthermore, A2M was decreasing from no radiative damage patients
to that of RILT grade I to II, and the FGB expression in exosomes showed
positive correlation with RILT from low to high level. The patients with low
FGB expression in plasma exosomes could tolerate higher radiative dosage
until the FGB was upregulated in plasma. Conclusion: LC-MS is an efficient
method for exosomal proteomics analysis and we reveal two stable targets
A2M and FGB, which could indicate the potential of patients suffering RILT
after radiotherapy. The two novel targets could serve as promising diagnosis
biomarkers for avoiding RILT.
Keywords: radiation-induced lung toxicity, Exosomal proteomics
POSTER SESSION 2 – P2.01: BIOLOGY/PATHOLOGY
PROTEINS IN LUNG CANCER AND PROTEOMICS –
TUESDAY, DECEMBER 6, 2016
P2.01-034 THE PREGNANCY ASSOCIATED ENDOMETRIAL PROTEIN
Copyright © 2016 by the International Association for the Study of Lung Cancer
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