1. The document discusses biomarkers for oral cancer detection, including functional and salivary biomarkers. 2. It presents a case study on NMR signatures of abnormal choline metabolism in oral squamous cell carcinoma that shows increased choline breakdown products but no significant change in lactate, suggesting no prominent Warburg effect. 3. The study finds that trimethylamine N-oxide and malonate could serve as important biomarkers for oral cancer.

1. Presented by
Sakshi Saxena
IBT VIth sem
ASU2013010200124

2. 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.

3. • 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

4. • 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

5. 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.

8. 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.

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

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

12. Received 23 February 2015
Available online 11 March 2015

13. 1. Considerations under study : Choline Metabolism and
Warburg effect
The study aims explored abnormal signatures in choline
metabolism in oral squamous cell carcinoma (OSCC)
2. Technique used : 1H and 13C NMR
3. Analysis : serum.

14. •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 choline
phospholipid 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

15. 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

19. 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.

20. 1. Trimethylamine N-oxide, the choline breakdown product and malonate
could 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.

21. 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, Amit
Basak, Amit Kumar Das, Mousumi Pal, Rita Banerjee, Ranjan Rashmi Paul, Jyotirmoy
Chatterjee. 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).