Biomarkers are broadly classified into genomics, proteomics, and metabolics. This helps in easy identification of malignancy in cancer patients. Oral cancer is major common cancer affecting in mouth, tongue, nasal cavity. Since it survival rate is low, it has to be detected early. Many biomarkers are currently used namely salivary. Serum, urinary etc. This article review all the markers used in oral cancer. Based on function and applications biomarkers in oral cancer are used mainly in diagnosis, prognosis, prediction, preventing, carcinogenic activity, malignancy phases
A biomarker is an non-invasive fluid which acts as indicator in case of any biochemical, biological changes i.e. it may increase or decrease or any response to a body .Mainly it indicates specific response in the body which might be a molecule or any type of secretion which is used for diagnosis .e.g. in cancer, biomarkers acts as a tool for cancer detection or preventive measures in patients1.this can be identified only by comparison studies of healthy individual with disease patients which represents the absence of presence of markers2.oral cancer a type of cancer which occurs in mouth , tongue or nasal cavity .where any cancerous tissue or lesion develops. According to survey,90/ of them are considered as oral squamous cell carcinoma .when compared to all oral tumours3.in oral cancer ,biomarkers has the main advantage of easily identifying the primary( pre malignant) and secondary (malignant) lesions or cancerous agent and also determines the levels of all chemical or any DNA changes (structural functional and, chemical abreaction )etc which acts as a ready identification of oral cancer4
. Biomarkers are broadly classified into genomics, proteomics, and metabolic s 5
.salivary biomarkers which is a non invasive fluid acts as a primary detection since it has a direct contact with tissue or lesions present .where saliva contains protein such as m RNA DNA .so this becomes the potential biomarker6..
serum biomarkers in oral cancer act as a early prediction in some cases, this marker can be identified only when the tumor or lesion starts to develop .as the tumor grows ,serum changes it amount and molecules or proteins present becomes synthesized which gets released with components7.a study was to made to identify the serum immune levels in cancer patients. A comparative study was made on pre and post treatment with certain protein levels such as AGP and IGA .where these proteins elevated in cancer patients and did not change even after treatment8
.urinary biomarker another type of markers used for the screening of oral cancer. where urine excreted product contains certain nicotine ,no2+no3 which are main chemicals present in tobacco products these are identified by methods such as hplc ,tlc .a study found these levels were significantly increased in oral cancer patients9
.proliferation markers such as ki -67 and p35 .considered as the evaluating agent for biological activities or changes take in oral cancer. This study was made by Histo pathological analysis( tumor size, metastasis, nodal size).where expression of markers were compared .so results concluded as useful marker 10.
So all Biomarkers in oral cancer is easily influenced by its risk factors ,sign and symptoms etc. this becomes another challenging opportunity for research in identifying specific , early marker and also detection of their stages(malignancy).so biomarkers acts as diagnosing agent11.
salivary biomarkers which is a non invasive fluid acts as a primary detection since it has a direct contact with tissue or lesions present .where saliva contains protein and analytes such as m RNA, DNA so this becomes the potential biomarker6,12.saliva comprises 99 percent of the water ,inorganic and organic components. Inorganic species does not give much effect where organic species contain abnormal development take place with changes in chemical abbreations (DNA aneuploidy).this DNA changes directly links to stages of cancer and can be easily predicting its negative potency13.
There are 8 tumor markers present in saliva namely
These markers get abruptly decreased or increased and this is identified by salivary analysis methods. A study was made and compared among these marker to check their sensitivity and specificity. Where five of the markers get increased and three becomes decreased. Results concluded that sensitivity ranges from (58-100) and specificity ranges from (42-10.) Which determines that? Each marker has their own value14. A case study showed the comparison between salivary LDH and serum LDH in oral squamous cell carcinoma patients with control group. Results proved that only oral squamous cell carcinoma patients have a consistent increase in both serum and salivary LDH and their isoenzymes15. But however salivary Iso enzymes have been extensively used as their studies was done in oral lichens also. Salivary Iso enzymes such as LDH4, LDH5.LDH3 .these Iso enzymes were found to be increases in oral lichen planus and the reason was LDH with its carcinogenic promoting activity in LDH16.
Two types of biomarkers are classified and divided in salivary markers
• Protein marker
• RNA based marker
Protein marker includes mainly three important markers
• Glutathione transferase
RNA roughly includes
• M RNA
• Micro RNA’S17.
SALIVARY RNA biomarker
Studies suggested that Human RNA is found in saliva. It is confirmed by two methods of microarray technique
• QPCR(Quantitative )
• High density nucleotide
This is done by collection of saliva sample from patients which gets separated by centrifuge methods to get a supernant liquid .then the product is analyzed by the above method. To indicate the presence. Results proved that M RNA is present in saliva and becomes the detection / prevention in oral cancer18. Specificity and sensitivity of RNA was found to be 99 percentages for early prognosis19.
MIRNA found in saliva is determined by micro array technique. The MIRNA play a role as marker in saliva by abnormality changes or impairment with cancerous transformation. Apparently MIRNA consists of 23 components with different but particular gene between oral cancer and normal cells.
Examination of cells expressed that eight molecules were increasing (
) and two molecules were decreasing the quality of cellular components which might be either RNA or proteins.
This specifically indicates a particular cell mir-10b which has the both activity of invading and migrating process. So this mir10-b actively participates in detection and early possibility of oral cancer20.
SALIVARY Long Non Coding RNA
Long non coding RNA is non –coding group of RNA containing greater than 2000 nucleotides. Their function or activity takes place by the chemical or biological mechanism which include differential expression of particular gene, transformation (epigenetic) in the nucleus etc
By considering all the factors lnc RNA plays a role in the development of sign and symptoms in oral cancer21. Six lnc RNA components were found where MALAT-1 and HOT AIR are mainly determined. These both are used for the determination on saliva from oscc patients22.
So, a experiment was conducted to find whether lnc rna is present in saliva or not. Saliva sample was withdrawn from oscc patient’s .In which 4 patient with lymph node malignancy determined for LNC RNA
Some sample revealed positive results. Where MALAT were significantly present in all patients .similarly HOT AIR was also present in half of all the patients. By calculating, the saliva contains minimum amount which can be used as potential biomarkers23.
CYTOKINES AND CHEMOKINES AS MARKER
Cytokines are produced and secreted by active immune complex namely t cells and t helper cells. These are small molecular protein intended to regulate In immune system. They take part as role in immune system.24.
Cytokine plays a important role as development and differentiation .it includes other cells such as interleukin- 7,interleukin-15,interleukin-12,interleukin-23,interleukin-2725.cytokines are further divided into
• Epithelium (IL-6,IL-8)
• Endothelium (IL-4, IL-10) these are mainly studied for presence in oscc26.
So a study was conducted and compared to evaluate the above interleukins i.e. between control and oscc patient. Results proved that IL-6, IL-8 was increased in oscc patients when compared with control group (p value was considerable to significance level)
Other cytokines such as IL-1alpha and other were also increased but was not equal to significance level .so in saliva IL-8 was considerably higher which is more or less used as a diagnosing oral cancer27
Chemokines are small receptors or secreted molecules which control the migrating phases in cancer /tumor cells in the body28. By using enzyme linked Immuno sorbent assay it was found that chemokines were found in saliva of oscc patients.
Chemokines are basically of two types
• Inflammatory (CXCCL-8,CXCCL-10,CXCCL-12)
• Haemostatic’s (CXCL-4, CXCL-14, CXCL18). These both were analyzed in cancer patients .where both chemokines were elevated.
But particular chemokines were active in form (CXCL-1, CXCL12, and CXCL18). These are not much proved which needs more research studies. Since it takes part in migrating phases and presence in saliva found to be useful marker in oscc and also used in clinical practice29.
• In Liver Butyrycholinertaerase is Synthesized by alpha glycoprotein ,where its serum level indicates it might increase or decrease.This acts as predicting marker in identifying the Malignancy which is significantly present in Oral Cancer.30
• Where interrelation matches of chlolinertaerase with significant Tumor including
Both differentiation and proliferation have been identified
• To find the presence of BCHE INS serum. This test is done between the healthy patient and biopsy proven OSCC patient. Blood is collected and centrifuged to get the serum to estimate the BCHE.
• Results indicates that preliminary treated patient serum BCHE level is increased
When compared to OSCC patient
• This BCHE level was found to be within significance level, so this has proved to be a predictive role in Oral cancer for Diagnosing.3
B-carotene which an act as powerful inhibitors of oxidation also called as Antioxidant plays a possible role in prohibiting the Oral cancer.32
Blood samples were taken from two groups
• OSCC patient Case study
• Health Control group
The blood Samples was collected and centrifuged to get the serum .It was then refrigerated, for confirmation of B-Carotene it is done by the Spectrometric Analysis.
Results revealed, patients showed decrease in level when compared with Controlled group. Even low level was found to be a preventing role in OSCC for detection.33
GLUTATHIONE SERUM.TRANSFERASE AND GLUTATHIONE REDUCTASE
GLUTATHIONE SERUM TRANSFERASE is a cancer indoctrinate gene. Main role of glutathione serum tranferase is to make complete or abrupt withdrawal of tobacco Carcinogen34.
Analyses of both glutathione serum transferase and glutathione reductase were found in serum.
This analyze was made in 100 controlled patients
• First Group-Proven oral cancer
• Second Group-Signs and Symptoms of Oral cancer
• Third Group-Healthy but tobacco user
• Fourth Group-Controlled patients
All group showed difference levels of glutathione serum tranferase and glutathione reductase, no significance levels was proved .Though particularly only glutathione serum transferase was increased in Stage 4.Different levels and transformation in Glutathione serum transferase plays a potential role or possible ,marker in OSCC .35
MIR-23 was found to be increased in plasma with oral cancer patient.
This study was found when identifying plasma MIRNA circulating process by Micro array technique
Studies were compared with normal and controlled patient of plasma RNA..Similar Authentication proved that MIR-23 was abruptly present which acts as a tumor or malignancy inhibitory agent. So this is a useful marker for screening in oral cancer36
URINARY BIOMARKER AND OXIDATIVE STRESS
• This Oxidative Stress also plays a role in Oral Cancer .Reactive oxidative species inducing oxidative stress alters the chemical changes happening in pre and cancerous transformation malignancy37
• Our study documented that there is a affiliation between Oxidative stress and urinary hydroxyl -2-deoxyguanosine.This is a non invasive marker where oxidative damage or stress is high .These are both are interlinked together and acts as marker for identification in OSCC38.
• .Human Papillomavirus type-16 related biomarker (p16INK4a) 39.
• Cyfra 21-1 and TPS tumor markers40.
By understanding all the methods of comparison and studies. More biomarkers are used recently. Further more research has to be done in biomarkers of oral cancer for their easy identification, prognosis, detection which decreases the mortality rate or prevention in cancer patients.