Seminar title:BLOOD-BASED BIOMARKERS FOR EARLY

DETECTION OF LUNG CANCER

PRESENTED BYShubham Vashishtha (123802)

PROJECT GUIDEDr Saurabh Bansal

Assistant Professor

Jaypee University of Information technology

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).

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.

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.

• 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

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

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

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.

Present Day tools for early detection of Lung CancerMethodology followed

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.

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.

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.

Present Day tools for early detection of Lung CancerLiquid biopsy :

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)

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.

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.