1. Seminar title:
BLOOD-BASED BIOMARKERS FOR EARLY
DETECTION OF LUNG CANCER
PRESENTED BY
Shubham Vashishtha (123802)
PROJECT GUIDE
Dr Saurabh Bansal
Assistant Professor
Jaypee University of Information technology

2. Introduction
• Lung cancer is one of the most common types of cancer reported with high
mortality rate.
• Leading cause of death: 158,080 death in both males and female reported in
2016 in US.(Cancer Statistics, 2016).
• In India, lung cancer constitutes 6.9 per cent of all new cancer cases.
(Prabhat et al., 2015).

3. What is Lung cancer?
• Cancer is a group of disease leading to abnormal cell growth.
• Lung cancer is the cancer in lung cells and are of two type:
• Small Cell Lung Cancer (SCLC) (12%)
• Non-Small Cell Lung Cancer (NSCLC) (87%)
• Adenocarcinoma
• Squamous cell cancer
• Large cell carcinoma
• Caused due to activation of oncogenes and suppression of tumor
suppression genes.

4. Constraints with Cancer survival rate
• Cancer affects cell growth and death metabolism.
• It is very difficult to differentiate between normal and cancerous
cell.
• Symptoms arrive at later stages.
• Rare chances of early detection of cancer is the leading cause.

5. • Chest x-ray.
• CT scan or combined PET–CT scan.
• Cytopathology examination of pleural fluid or sputum.
• Usually bronchoscopy-guided biopsy and core biopsy.
• Sometimes open lung biopsy.
Common diagnostic methods

6. MicroRNAs
• Small endogenous non-coding RNA of 18-25 nucleotide length.
• Act as regulators of gene expression at post transcriptional level.
• Reported to be involved in multiple cellular processes including
cell proliferation, differentiation and apoptosis. (Pritchard CC et
al.,2012).
• Aberrant expression of miRNA associated with various
carcinogenesis including NSCLC.
Present Day tools for early detection of
Lung Cancer

7. MicroRNAs
• Meta-analysis showed 0.75 (95% CI) sensitivity and 0.79 (95% CI)
specificity in NSCLC diagnosis represents high accuracy.(H Wang et
al.,2015).
• miRNA have good stability and is found in abundance in blood.
• Cost effective, convenient and powerful biomarkers found in blood, Thus
need a simple blood test.
• Better diagnostics accuracy in Caucasian population then Asian population
• Multiple miRNA assays are more accurate than single.
Present Day tools for early detection of
Lung Cancer

8. Present Day tools for early detection of
Lung Cancer
MicroRNAs : Example Studies
1. MicroRNA 486 and 150 used as biomarker for Early Diagnosis
tools.(Wanshuai Li et al., 2015).
• 10 miRNA were taken in consideration.
• Study performed on 11 patients and 11 controls.
2. Micro RNA-21 present on chromosome 17q23.1used as tool for lung
cancer diagnosis. (LI et al.,2011).
• 10 patients and 10 controls were considered.

9. Present Day tools for early detection of
Lung Cancer
Methodology followed

10. Present Day tools for early detection of
Lung Cancer
MiRNAs: Study 1
• MiR-486 and miR-150 were significantly increased in plasma of
NSCLC patients.
• High correlation was seen in between the expression levels of
miRNA in blood and tissue.
• Sensitivity and specificity of miRNA-486 (0.92, 0.909) & miRNA
150 (0.752, 0.818) was high.
• Plasma levels of miR-486 and miR-150 can be potential bio-markers
for early diagnosis of NSCLC patients.

11. Present Day tools for early detection of
Lung Cancer
MiRNAs: Study 2
• The expression level of miR-21 was 1947.26 pg/ml in lung cancer
patients and 943.42 pg/ml in controls.
• 78.8 % sensitivity was seen in the study which is high.
• For regular pathology tests the sensitivity is low but miRNA can be
used as potential biomarkers.
Note: Currently miRNA diagnostic is under trials and is not in clinical use.

12. Present Day tools for early detection of
Lung Cancer
Liquid biopsy : circulating free DNA (cfDNA) and tumor cells
• Cancer cells stray cells and traces of DNA in bodily fluids when they die.
• Present day advancement uses these samples in order to detect the presence of
cancer before its symptoms appear
• Helpful for population with risk factors.
• Better efficiency, cost effective, time consuming and painless then
traditional biopsy technique.
• Uses blood, urine and spinal fluid as samples.

13. Present Day tools for early detection of
Lung Cancer
Liquid biopsy :

14. Present Day tools for early detection of
Lung Cancer
Liquid biopsy :
• Amplification and then next generation sequencing is done in order to
detect the mutations in the DNA
• Common mutations in oncogenes detected are:
• EGFR (Epidermal Growth Factor Receptor)(15-35%)
• KRAS (Kirsten rat sarcoma viral oncogene)(7-10%)
• ALK1 (Anaplastic lymphoma kinase)(5-10%)
Note: Liquid Biopsy Receives Approval by Food and Drug
Administration on July 19, 2016 for EGFR mutations
Source: (Journal of the American Medical Association JAMA)

15. Conclusion
• Blood based markers will lead to
• Detection of cancer at early stages.
• Reduce death rate and increase survival rate of patients.
• Reduce time and cost of treatment and diagnosis.
• Make process more efficient and sensitive.
• Great deal of knowledge.

16. References
• Prabhat Singh Malik and Vinod Raina2, “Lung cancer: Prevalent trends & emerging concepts”, Indian
J Med Res. 2015 Jan; 141(1): 5–7.PMCID: PMC4405940
• Siegel RL, Miller KD, Jemal A.,“Cancer statistics, 2016”,CA Cancer J Clin. 2016 Jan-Feb;66(1):7-30.
doi: 10.3322/caac.21332. Epub 2016 Jan 7.
• Pritchard CC, Cheng HH, Tewari M. “MicroRNA profiling:approaches and considerations”. Nat. Rev.
Genet. 2012; 13: 358–69.
• Huoqiang Wang, Songnian Wu, Long Zhao, Juan Zhao, Jinjun Liu1 And Zhihao Wang. “Clinical use of
microRNAs as potential non-invasive biomarkers for detecting non-small cell lung cancer: A meta-
analysis”. Respirology (2015) 20, 56–65 doi: 10.1111/resp.12444
• Li W, Wang Y, Zhang Q, Tang L, Liu X, Dai Y, et al. (2015) MicroRNA-486 as a Biomarker for Early
Diagnosis and Recurrence of Non-Small Cell Lung Cancer. PLoS ONE 10(8): e0134220.
doi:10.1371/journal.pone.0134220
• Yanzhao Li1, Wen Li1, Quchang Ouyang, Shunqin Hu And Jianxin Tang “Detection of lung cancer
with blood microRNA-21 expression levels in Chinese population” Oncology Letters 2: 991-994, 2011
• Michael Tu, David Chia, Fang Wei, and David Wong. “Liquid Biopsy for Detection of Actionable
Oncogenic Mutations in Human Cancers ” Analyst. 2016 January 4; 141(2): 393–402.
doi:10.1039/c5an01863c.