Presented bySakshi SaxenaIBT VIth sem

ASU2013010200124

Introduction to Oral cancer.

Introduction and application of biomarkers to

Oral cancer.

Overview of functional biomarkers for oral

cancer.

Overview of salivary biomarkers for oral cancer.

Case study : NMR (1H and 13C) based signatures

of abnormal choline metabolism in oral squamous

cell carcinoma with no prominent Warburg effect.

• Oral cancer, a subtype of head and neck cancer, is a cancerous tissue

growth located in the oral cavity.

• More than 90% of oral cancers are squamous cell carcinoma (OSCC)

originating in the tissues those line the lips, the oral cavity, and

pharynx.

• OSCC is characterized by a high degree of local invasiveness and a

high rate of metastasis to the cervical lymph nodes.

• The Indian subcontinent accounts for one-third of the world burden of

this malignancy.

• A high prevalence of oral cancer in India and other Asian countries is

mainly due to influence of region-specific epidemiological factors

such as tobacco and betel quid chewing.

student.ahc.umn.edu

• The United Nations’ World Health Organization defines a biomarker

as

“Any substance, structure or process that can be measured in the

body or its products and influences or predicts the incidence of

outcome or disease.”

Applications for oral cancer

• 1. Biomarkers help in evaluating the preventive measures or therapies and

the detection of the earliest stages of oral mucosal malignant

transformation.

• 2. Reveal the genetic and molecular changes related to early, intermediate,

and late end-points in the process of oral carcinogenesis

• 3. Refine the ability to enhance the prognosis, diagnosis, and treatment of

oral carcinomas - Monitor progression/ recurrence, treatment compliance

• 4. Useful in early stages of cancer drug development

• 5. Determine efficacy and safety of chemo preventive agents

The biomarkers could be classified into five groups based on their

biological functions:

1) Cell cycle progression and proliferation;

2) Tumor suppression and apoptosis;

3) Hypoxia;

4) Angiogenesis;

5) Cell adhesion and matrix degradation.

Salivary biomarkers

Saliva is a valuable body fluid for disease diagnosis due to its noninvasive nature, and has been increasingly used as a source for discovery of oral cancer biomarkers.

Bano, et al.: Salivary Biomarkers for Oral Squamous Cell Carcinoma: An Overview

Bano, et al.: Salivary Biomarkers for Oral Squamous Cell Carcinoma: An Overview

Received 23 February 2015Available online 11 March 2015

1. Considerations under study : Choline Metabolism and Warburg effect

The study aims explored abnormal signatures in cholinemetabolism in oral squamous cell carcinoma (OSCC)

2. Technique used : 1H and 13C NMR

3. Analysis : serum.

•Activated choline metabolism is characterized by increased phosphocholine (PCho) and total choline-containing compounds (tCho) which are referred to as the cholinic phenotypes, is a fairly new metabolic hallmark.

•Phosphocholine, a precursor as well as a breakdown product of phosphatidylcholine(PtdCho),together with other phospholipids such as phosphatedylethanolamine (PtdEtn) forms the characteristic bi-layer structure of cellular membranes and regulates membrane integrity.

•Indeed, choline metabolism, a network of transporter systems and enzymes involved in cholinephospholipid metabolism are deregulated in cancer cells. Hence, choline metabolism including expression of its precursors and break-down products are remarkably disturbed in malignant conditions. www.dougcookrd.com

Warburg theory of cancer, postulates that the driver of tumorigenesis is an insufficient cellular respiration caused by insult to mitochondria.

The term Warburg effect describes the observation that cancer cells, and many cells grown in-vitro, exhibit glucose fermentation even when enough oxygen is present to properly respire.

In other words, instead of fully respiring in the presence of adequate oxygen, cancer cells ferment.

www.charliefoundation.org

1. Crosstalk between the oncogenic pathway [such as COX2, ERBB2, RAS, MAOK,HIF1] and choline metabolism is deregulated in malignant cells due to increase demand of choline in rapidly proliferative cancerous cells.

2. More utilization of choline by cancerous cell in OSCC generates more break-down product of it.

3. Warburg effect is not observed since no significant change in lactate is observed.

4. Increased Malonate due to alternate pathway taken up by the OSCC cells.

1. Trimethylamine N-oxide, the choline breakdown product and malonatecould be important biomarker in oral cancer.

2. No significant changes in Lactate but in Malonate can be another biomarker specific to Oral Cancer since halllmark of cancer : Warburg effect has not been observed.

1. NMR (1H and 13C) based signatures of abnormal choline metabolism in oral squamous cell carcinoma with no prominent Warburg effect. Swarnendu Bag, Deb Ranjan Banerjee, AmitBasak, Amit Kumar Das, Mousumi Pal, Rita Banerjee, Ranjan Rashmi Paul, JyotirmoyChatterjee. Biochemical and Biophysical Research Communications 459 (2015) 574e578. 11 March 2015

2. Masumi Tsuda and Yusuke Ohba (2012). Functional Biomarkers of Oral Cancer, Oral Cancer, Dr. Kalu U. E. Ogbureke (Ed.), ISBN: 978-953-51-0228-1, InTech, Available from: http://www.intechopen.com/books/oralcancer/functional-biomarkers-of-oral-cancer.

3. Salivary Biomarkers for Oral Squamous Cell Carcinoma: An Overview. Sidra Bano, Maria Priscilla David, AP Indira. IJSS Case Reports & Reviews | January 2015 | Vol 1 | Issue 8

4. Salivary Markers for Oral Cancer Detection. Article in The Open Dentistry Journal · August 2010. DOI: 10.2174/1874210601004010172 · Source: PubMed

5. The early diagnosis and monitoring of squamous cell carcinoma via saliva metabolomics. Wang, Q., Gao, P., Wang, X. & Duan, Y. Sci. Rep. 4, 6802, DOI:10.1038/srep06802 (2014).