•lung cancer ( both small cell and non-small cell) is the most frequent cause of cancer death -American women and man •Romania –10.000 new cases… [618043]

microRNAs as Next Generation
Biomarkers for Lung Cancer
Iurca Ioana

General overview
•lung cancer ( both small cell and non-small cell) is the most
frequent cause of cancer death -American women and man
•Romania –10.000 new cases /year
•rates increasing in the past 10 years
•non specific symptoms, until far advanced
•75% of lung cancers are recognised => locally advanced or
metastatic stages => less than 15% five -year overall survival
rate

MicroRNAs -“you can change a phenotype by
modulating a single miRNA ” Thomas Wurdinger , HMS
•class of small noncoding RNA molecules
•~22 nucleotides fragments controlling genes expression by
binding to mRNA
•degrades or inhibits proteic synthesis of mRNA
•role in disease still in research ( cancer)
•> 2500 types
•revealed in serum, sputum
•function as promoters or inhibitors of tumor gene according
to substrate -protoncogenes TSG
•controlled by other epimechanisms
•posttranscriptional event
•www.mirbase.org

•A meta -analysis of 20 published miRNA studies in lung
cancer -> total = 598 tumor , 528 non -cancerous control
samples, they identified a statistically significant miRNA
signature of seven upregulated (miR -21, miR -210, miR –
182, miR -31, miR -200b, miR -205 and miR -183) and 8
downregulated (miR -126-3p, miR -30a, miR -30d, miR -486-
5p, miR -451a, miR -126-5p, miR -143 miR -145)
•this meta -analysis reaching is suited and adequate solution
for identification of expressing miRNA meta -signature by
conecting certain distinct miRNA expression research
•This study is particular to comparison of tumor and
noncancerous tissues only.
•It would be interesting to evaluate miRNAs correlated with
progression free survival, staging, prognostic, clinical
response to treatment.

Potential miRNA for Lung cancer
•serum -miR-21-3p, -205-5p, -205-3p, -141, 200c
-miR -24, -205, -30d
•plasma -miR-21, -155, miR 145
•exosome -miR-17-3p, -21, -106a, -146, -155, -191,-192, -203, -205, –
210, -212, -214
•sputum -miR-205, -210, -708
Plasma miRNAs
–define risk for lung cancer in asymptomatic initial stages
–diagnose lung cancer in screen identified nodules -80%
efficiency
–define expectation of life in screen -detected lung cancer

MicroRna expression in cancer
•12 years ago was reported the first association between miRNAs and
cancer by Calin et al
•fundamental biomarkers that may control >30% of human genes and could
be a part of the massive cancer puzzle
•adjustement of miRNA expression have been seen in
hcc, lung, breast, stomach, pancreatic cancer progression and
chemoresistance
• expression will decline the establishment and translatability of the
target tumor suppressor mRNA
Principle -> decreased expression of the tumor suppressor
Development tumor formation
• expression of the miR will regulate transcript stability of the target
oncogene mRNA
Leads to increased expression of the oncogene
Increased tumor evolution

let-7 miRNA
•first in human
•suppress expression RAS, MYC, HMGA 2,
CDK6
•generally reduced in human lung cancers
•reduced let-7miRNA expression was very
much correlated with reduced postoperative
survival
•Overexpression of let-7miRNA in A549 lung
adenocarcinoma cell line repressed lung cancer
cell growth in vitro

miR -21
•upregulated miRNAs -> solid tumours ; overexpressed -leukemia
•Jiang et al revealed that endogenous miRNAs are strongly present in
the patients sputum
•initiates cancerogenesis over suppressing of multiple negative
regulators of RAS/MEK/ERK pathway and suppression of apoptosis
•miR-21 was found to be substantial in sputum of NSCLC patients
as compared with tumour -free subjects
•the same study it was shown that miR -21 overexpression in sputum
was a more responsive biomarker (70%) than current sputum
cytology (48%) in determining lung cancer
•Markou and co found that overexpression of mature miR-21was an
autonomous negative prognostic factor for global survival in NSCLC
patients
•overexpressed miR-155in lung cancer cells correlated with reduced
patients expectation of life
•relevant role in evolution of heart condition

miR-155
•B-cell malignancies
•transcribed from a noncoding RNA BIC
•physiologically, miR -155 is a necessary partcipant in
hematopoiesis , the immune response and inflammation .
•upregulated in several types of malignancies
•has an important role in pathogenesis of B cell diseases.
•the oncogenic objective of miR -155 can be interpreted by its
spotted genes and the involved underlying molecular
pathways conferred in
•overexpression of miR -155 in mice results in expansion of
lymphoproliferative diseases, at the same time following
withdrawal induces remission

miR-200 Family
-miR-200a, miR -200b, miR -200c, and miR -429
-role in the promotion of EMT.
-regulation of ZEB
-transcription factors (ZEB1 and ZEB2),
-E-cadherin
-vimentin
-the down -regulation promotes EMT in the
progression of lung cancer

Conclusions
•role of several miRNAs are currently under
investigation in
diagnostic, prognostic, predictive value for
numerous categories of cancer
•miRNAs expression could represent an useful
appliance to clarify examination of oncogene
addicted NSCLC
•clinical advantages requires considerable
contribution in effort and capital approaching
biomarkers driven clinical trial

Thank you!