Creatine  phosphokinase levels in Oral cancer Patients

 

Nauma Hafeez

Biochemistry, Saveetha Dental College, Chennai  

Corresponding Author E-mail : naumahafeez10@gmail.com

 

ABSTRACT:

AIM: to evaluate the presence of Creatine  phosphokinase in oral cancer patients using their serum samples.

Material and methods:15 samples of oral cancer serum,15 samples of normal serum,CPK test kit. Results and discussion : this study showed that CPK levels were much higher than that of normal patients.  Oral cancer survival rate has not improved in the last 40 years, despite recent advances in surgical procedures , technological progress in the world of medicine and the availability of new chemotherapeutic agents. Therefore this method can be used as an effective method to diagnose oral cancer and can be used as an effective biomarker for oral cancer. 

 

KEYWORDS :  Oral Cancer , CPK Levels , Biomarker.

 

 


 

INTRODUCTION

Every cell type has a unique molecular signature, referred to as biomarkers, which are identifiable characteristics such as levels or activities (the abilities of genes or proteins to perform their functions) of a myriad of genes, proteins or other molecular features. Biomarkers are therefore, an objective measure or evaluation of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention(1). This includes all diagnostic tests, imaging technologies, and any other objective measures of a person’s health status.(7,8).

 

Bio markers are finding spot in effectively diagnosing cancers especially those related to muscles and thereby increasing life expectancy in patients with first stage of cancer. There are various types of biomarkers available with the advance in the field of biochemistry for example Cytogenetic and cytokinetic markers, Genetic biomarkers, Epigenetic biomarkers and cells themselves acting as biomarkers.

 

Alterations primarily in three main classes of genes viz., (proto) oncogenes, tumour suppressor genes and DNA repair genes collectively contribute to the development of cancer genotype and phenotype that resists the natural and inherent death mechanism(s) embedded in cells (apoptosis and like processes), coupled with dysregulation of cell proliferation events. Cancer cells display a broad spectrum of genetic alterations that include gene rearrangements, point mutations, and gene amplifications, leading to disturbances in molecular pathways regulating cell growth, survival, and metastasis(8) Technologies to recognize and understand these signatures of normal cells and how these become cancerous can help  provide important insights into the etiology of cancer that can be useful for early detection, diagnosis, and treatmen(7). Biomarkers are therefore invaluable tools for cancer detection.

 

More than 90% of the oral cancers are squamous cell carcinomas (OSCC), which arise from the epithelial lining of the oral cavity. Even though the oral cavity is easily accessible for direct visual examination, most OSCCs are not diagnosed until an advanced stage, which is believed to be the major reason for the low survival rate.(1)

 

The death rate for oral cancer is higher than that of cancers which we hear about routinely such as cervical cancer, Hodgkin's lymphoma, laryngeal cancer, cancer of the testes, and endocrine system cancers such as thyroid, or skin cancer(9).

 

In advanced stages of tumors, cells starts appearing in bloodstream where it can be easily monitored. Advanced clinical practice in certain malignancy have effectively used tumor and immune cells where it served as a good biomarker of prognosis, while its utility in other cancers are under evaluation at the present time. Survival of patients with Oral cancer  has not improved in the last 40 years, despite recent advances in surgical procedures, technological progress in the world of medicine and the availability of new chemotherapeutic agents. In addition, surgical resection results in significant functional and cosmetic defects; therefore, it is important to develop conservative therapeutics, whereupon identification of markers representing oral cancer aggressiveness would be worthwhile to decide the most suitable treatment for each patient from therapeutic options. Therefor biomarkers are key to diagnosis. (11).

 

In this study we are looking at CPK as a biomarker. Over the past years, a concept for creatine kinase function, the 'PCr-circuit' model, has evolved. Based on this concept, multiple functions for the CK/PCr-system have been proposed, such as an energy buffering function, regulatory functions, as well as an energy transport function, mostly based on studies with muscle. While the temporal energy buffering and metabolic regulatory roles of CK are widely accepted, the spatial buffering or energy transport function, that is, the shuttling of PCr and Cr between sites of energy utilization and energy demand, is still being debated(10). though there still seems to be a confusion on the exact role of CPK ,it is however safe to say that it is strongly related to muscles and thus justifies its use as an oral cancer biomarker. Creatine kinase (CK), an enzyme, is expressed by various cells and tissues(3). CK, which is crucially involved in a plethora of bio  nergeticprocesses, is particularly important and is expressed at high levels in cells with high energy requirements such as skeletal, cardiac and smooth muscle, kidney, brain and neuronal cells, retina photoreceptor cells, spermatozoa and sensory hair cells of the inner ear (5,6)

 

As reported, CK is an important regulator of T cell development and activation which is an important factor in immune response.(2). Therefore low CPK could indicate a weak immune system and therefore the patient is more prone to diseases. Creatine (Cr) has emerged as a safe nutritional supplement not only to increase muscle mass and performance, prevent disease-induced muscle atrophy and improve rehabilitation, but also to strengthen cellular energetics in general(4)

 

The above information  shows the association of CPK and muscles and endothelium therefore showing the reason behind the instincts of choosing CPK as a biomarker in oral cancer.

 

METHODS AND MATERIALS:

This experiment required 30 volunteers in total, of which 15 were normal patients and 15 were patients having oral cancer. CPK test was performed on the patients

 

INSTRUMENTS : Beckman Coulter UniCel® DxC800 Synchron Clinical System

 

MATERIALS:

1)    Beckman Micro Tube

2)    S/P Plastic Transfer Pipette

3)    S/P Brand Accutube Flange Caps

4)    CPK reagent

 

Method

·      Collect serum samples from 15 oral cancer patients and 15 normal volunteers

·      Label Micro tube (CX tube) and transferring serum .

·      Adding reagent

·      Analyzing serum

·      Recording of Data

 

Volunteers participating in this study were not forced in any way. Procedure and reason of study was explained to the volunteers prior to blood sample collection.

 

Criteria For Selection of Normal and Healthy Individuals :

The patients were chosen between the ages 40 -50 years so as to make a comparison with the oral cancer patients who tend to fall in this age group.Patients under this age group were randomly chosen without any bias.

 

Criteria for Selection of Oral Cancer Patients :

The patients with oral cancer were chosen. These patients naturally into the senior age group that is from 40 -50 years.  There was no bias during selection. Patients were aware of this study's aim and were not forced into the study in any way.

 

RESULTS:

Table 1   

 

Mean

Standard Deviation

Standard Error Mean

NORMAL PATIENTS

76.67

34.19

8.828

ORAL CANCER PATIENTS

516.2

278.64

71.945

 

Table 2

Group

Number of Patients

Mean Rank

Sum of Mean Rank

Normal Patients

15

8.07

121

Oral Cancer Patients

15

22.93

344

Total

30

 

 

 

DISCUSSION:

Patients volunteering to take part in this research are aged between 40-50 years. The volunteers show normal CPK levels that is within 0-190 IU/L the CPK levels in patients suffering from oral cancer. There were 15 participants in this category 9 males and 6 females. The patients participating are aged between 40-50 years. The volunteers have very high levels of CPK only one patient has CPK value that lies in the normal range. 

T Test

This table-1 shows the mean values of CPK in the normal volunteers and oral cancer patients. The table clearly shows the large difference in their CPK levels. Normal patients are seen to have values between the normal range that is 0-190IU/L.  The mean value of the normal patients is 76.67 with an error of 8.828 which is negligible. The standard deviation of the normal patients shows that all the CPK levels of all  patients falls between 76 (+ or - ) 34.19.  Oral Cancer patients on the other hand have a very high mean  level of CPK that is 516.2 with an error of 71.945. The high value of standard deviation which is 278.64 shows the wide range of distribution of CPK levels in these patients. The  graph 1 clearly shows the the high mean levels of CPK in oral cancer as compared to normal patients.

 

Mann Whitney U (Table2)

This test shows the significant difference in the serum CPK level of blood in normal and oral cancer patients. The mean rank in normal patients is 8.07 and the mean rank in oral cancer patients is almost 3 times more that is 22.93 . This shows the greater CPK count of oral cancer patients as compared to normal patients.

 

CONCLUSION:

This study was conducted in the hope of finding a relation between CPK and oral cancer and therefore a new and significant biomarker for early oral cancer detection. Oral cancer and CPK levels are interrelated directly . The above statistical data clearly shows that high CPK  levels in an individual is an indicative of oral cancer.  Knowing that CPK levels and oral cancer are directly proportional to each other is helpful in determining the advancement of the cancer. This enlightens the fact that CPK can be successfully used as a future oral cancer biomarker. With  further research, this biomarker can significantly help diagnose cancer at the earliest stage possible as tumours cause release of CPK in the body and thus will give a positive result for CPK test. Therefore this study can greatly influence the field of cancer in dentistry.

 

REFERENCES:

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7.           Anant  Narayan Bhatt, Rohit Mathur, Abdullah Farooque, Amit Verma,B.S. Dwarakanath. Cancer biomarkers - Current perspectives. Indian J Med Res 132. 2010

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10.        Wallimann T, Hemmer W.  "Creatine kinase in non-muscle tissues and cells". Molecular and Cellular Biochemistry. 133–135. 1994:193–220.

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Received on 08.06.2016             Modified on 21.06.2016

Accepted on 02.07.2016           © RJPT All right reserved

Research J. Pharm. and Tech 2016; 9(10):1577-1580.

DOI: 10.5958/0974-360X.2016.00310.3