Biomarkers for Oral Cancer

Carcinogenesis is a complex process that occurs at the

phenotype and genotype levels
Oral cancer, a subtype of head and neck cancer, is a
cancerous tissue growth located in the oral cavity
The Indian subcontinent accounts for one-third of the
world burden of this malignancy
Molecular level changes
Cancer cell proliferation without external stimuli
Insensitivity to inhibitory growth signals
Evasion of apoptosis or cell death mechanisms and/or
activation of anti‑apoptotic genes
Unlimited replicative potential
Sustained angiogenesis
Invasion and metastasis ability
Genomic instability
Protooncogenes mutation caused by defects in DNA repair.
Biomarkers
Any substances, structure or process that can be
measured in the body or its products and influences or
predicts the incidence of outcome or disease
 Biomarkers
Biomarkers can be used
for
estimating disease risk
screening for occult
primary cancers,
distinguishing benign from
malignant findings/one
type of malignancy from
another,
determining prognosis,
predictors/screening, and
monitoring disease status
Functional biomarkers for oral cancer
Classification based on their biological fuctions
Cellular biomarker
1) Cell cycle progression and proliferation
2) Tumor suppression and apoptosis
3) Hypoxia
4) Angiogenesis
5) Cell adhesion and matrix degradation
Humoral biomarker
1) Parathyroid hormone-related protein
2) Endothelins and their receptors
3) Inflammatory cytokines and chemokines
Cell cycle progression and proliferation
EGFR Overexpression Poor prognosis

Cyclin D1 Amplification Unfavourable overall

survival

Cyclin B1 Overexpression in Cervical lymph node

cytoplasm metastasis

Ki-67 Increase(early), Poor overall survival

decrease(late)

PCNA Positive No significant association

on survival

Akt Overexpression Poor prognosis

Tumor suppression and apoptosis
p53 Overexpression ,mutatio Poor prognosis
n

p27 Overexpression No significant association

on survival

Bcl-2 Negative Higher survival

Bax Positive Higher survival

Survivin Overexpression Aggressive and invasive

Hypoxia
HIF-1alpha Diffuse overexpression Good prognosis

CA IX Overexpression Recurrence with worse

survival

GLUT-1 High expression Worse overall survival

EPOR High expression Worse prognosis

Angiogenesis
VEGF Positive Poor prognosis

CD105 High expression Recurrence with worse

prognosis

CD34 Positive within tumor Cervical lymph node

nests metastasis

Eph A2 High expression Poor survival

Parathyroid hormone-related protein

PTHrP High expression Malignant conversion

 Endothelins and their receptors

Endothelins(Ets) Overexpression Tumor growth and

progression
ET aR, ETbR Overexpression Tumor growth and
progression
Inflammatory cytokines and chemokines

Interleukin (IL)-6 High expression Tolerance to immune

system
CXCL13 High expression Tumor development and
progression
Screening for oral squamous cell
carcinoma
Salivary biomarkers such as
L‑phenylalanine
Sphinganine
Phytosphingosine
S‑carboxymethyl‑L‑cysteine
Differential diagnosis
Proteomic marker CLAC2
Acidic laccase gene 2
Recurrence potential marker
CD34 expression
GRP78 protein expression
Thymidylate synthase (TS)
Predicting prognosis and distant
metastasis
Genomic biomarkers such as ITGA3 and ITGB4
expression
GRP78 protein expression
Phosphoprotein 53 (p53)
Epidermal growth factor expression (EGFR) and p53
Phosphoprotein 16 (cyclin‑dependent kinase inhibitor
2A) (p16)/cyclic D1 amplification
RAR alfa/phosphoprotein 21 (potent cyclin‑dependent
kinase inhibitor)
Identify therapeutic targets
p‑mTOR protein
GF 15 expression
Predicts radio‑resistance in oral squamous
cell carcinoma
Genomic markers such as
VEGF
BCL‑2
Claudin‑4
YAP‑1
c‑MET
METHODOLOGIES OF IDENTIFYING ORAL
CANCER BIOMARKERS

Identifying biomarkers from the tumor cell, tumor

microenvironment, tumor adjacent tissue, or by the
metabolism of pharmaceutical or therapeutic agents
METHODOLOGIES
DNA arrays
High‑throughput sequencing
Polymerase chain reaction
Gene expression arrays
Restricted fragment length polymorphism,
Ribonucleoprotein i m m u n o p re c i p i t a t i o n ‑ g e n e c h i p
Cross ‑ linking immune‑precipitation, liquid chromatography
Nuclear magnetic resonance
Mass spectroscopy
Enzyme assays
Immunohistochemistry
 CHALLENGES OF BIOMARKERS IN
CANCER STUDIES
Should be a unique indicator of malignancy
Should limit false‑positive tests and should produce
valid and reliable results
Many biomarkers fail because of clonal diversity,
genomic instability in cancer tissues, the
heterogeneous nature of cancer tissue, or incorrect
identification of the metastatic signature molecule
Thank you