|Year : 2016 | Volume
| Issue : 1 | Page : 11-14
Correlation of salivary levels of interleukin-6 and albumin with oral squamous cell carcinoma
Mallikarjuna Rao1, Amitha Ramesh2, Swathi Adapa2, Biju Thomas2, Jayarama Shetty1
1 Department of Radiotherapy and Oncology, KS Hegde Medical Academy, Mangalore, Karnataka, India
2 Department of Periodontology, AB Shetty Memorial Institute of Dental Sciences, Mangalore, Karnataka, India
|Date of Web Publication||25-Feb-2016|
Flat No. 53, Valerie Manor, Britto Lane, Falnir, Mangalore, Karnataka - 575 001
Source of Support: None, Conflict of Interest: None
Background: Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy and is the most common neoplasm arising in the upper aerodigestive tract. Earlier studies have shown that salivary levels of interleukin (IL)-6 were significantly higher in patients with oral squamous cell carcinoma (OSCC) when compared to healthy individuals. They were considered as useful biomarkers for early OSCC development. Albumin levels in the saliva were shown to be elevated in medically compromised patients with poor general condition and performance status. Aim: The purpose of this preliminary research is to investigate the role of IL-6 and albumin levels in the saliva as a marker for the early diagnosis and progression of OSCC. Materials and Methods: This cross-sectional study was conducted from December 2014 to May 2015. Sixty individuals were included and two groups (with 30 individuals each) were formed – Group 1: Healthy individuals and Group 2: Patients with OSCC. IL-6 and albumin levels in the saliva were measured using commercially available kits and were compared between the two groups using Mann–Whitney U test. P value of less than 0.05 was regarded to be statistically significant. Results: Mean value of IL-6 in Group 1 (healthy) was 15.06 [standard deviation (SD) is 4.42] and in Group 2 (OSCC) was 192.15 (SD is 82.76). On comparing the two mean values, it was seen that there was a significant rise in the salivary IL-6 levels in the OSCC group when compared to the healthy group. The mean value of albumin in Group 1 (healthy) was 0.28 (SD is 0.19) and in Group 2 (OSCC) was 0.82 (SD is 0.41). On comparing the two mean values, it was seen that there was a significant rise in the salivary levels of albumin in OSCC patients when compared to the healthy group. Conclusion: This study shows that IL-6 and albumin levels in the saliva can be used as useful biomarkers for OSCC.
Keywords: Albumin, interleukin (IL)-6, oral squamous cell carcinoma
|How to cite this article:|
Rao M, Ramesh A, Adapa S, Thomas B, Shetty J. Correlation of salivary levels of interleukin-6 and albumin with oral squamous cell carcinoma. J Health Res Rev 2016;3:11-4
|How to cite this URL:|
Rao M, Ramesh A, Adapa S, Thomas B, Shetty J. Correlation of salivary levels of interleukin-6 and albumin with oral squamous cell carcinoma. J Health Res Rev [serial online] 2016 [cited 2020 Mar 29];3:11-4. Available from: http://www.jhrr.org/text.asp?2016/3/1/11/177493
| Introduction|| |
Oral squamous cell carcinoma (OSCC) is common and one of the most dreaded types of cancer with high rates of mortality and morbidity all over the world. In India, the incidence rate is high due to consumption of tobacco in various forms, consumption of alcohol, cultural factors, and lack of awareness regarding oral health. Of all cancers in India, the incidence of OSCC is highest in males and third highest in females. Age-adjusted incidence rate of oral cancer in India is 20 per 100,000 in the population and accounts for over 30% of all cancers in the country. In the early stage of OSCC, high cure rates and survival rates can be achieved by surgery alone. But most of the patients present at an advanced stage where even combined modalities of treatment including surgery, radiotherapy, and chemotherapy can achieve only minimal cure and survival rates. So it is very important to diagnose OSCC at an early stage and also predict the progression by using salivary biomarkers. Various cytokines and growth factors play a significant role in pathophysiologic regulation of tumor growth and progression. Interleukin (IL)-6 is a multifactorial cytokine with a wide spectrum of immunologic activities, and is also a potential mediator of cancer cachexia.
Nuclear factor (NF)-Kb controls the production of IL-6. Some chronic inflammatory diseases, autoimmune disorders, and cancers can cause dysregulation of NF-Kb resulting in abnormal production of IL-6.,,
Earlier studies have shown that salivary levels of IL-6 were significantly higher in patients with OSCC when compared to healthy individuals. They were considered to be potential biomarkers for early OSCC development.
Albumin is regarded as a serum ultrafiltrate to the mouth, and it may also diffuse into the mucosal secretions. It was reported that salivary albumin levels were increased in medically compromised patients with a poor general condition. Salivary albumin levels were high in patients with diabetes, immunosuppression, and in patients who received radiotherapy.
The purpose of this research was to investigate the role of IL-6 and albumin levels in the saliva as a marker for early diagnosis and progression of OSCC.
| Materials and Methods|| |
The study was conducted in A.B. Shetty Memorial Institute of Dental Sciences and K.S. Hegde Charitable Hospital, Mangaluru, Karnataka from December 2014 to May 2015. Ethical clearance was obtained from Nitte University's ethical committee in October 2014. This study included 60 individuals and they were divided into two groups––Group 1 and Group 2, which included healthy, and OSCC subjects, respectively. They were explained about the details of the study in the language of their choice and were asked to sign the consent form.
Individuals with good oral health and general health were included in Group 1. Pathology reports of OSCC were collected from patients with OSCC.
Individuals with any other oral lesion, systemic disease, or with history of any antibiotic/anti-inflammatory/antidepressant therapy for 3 months prior to the study, and previous chemotherapy and radiotherapy to the oral cavity were excluded from study.
The screening was done by the medical and dental history of the subjects and it was recorded.
Collection of saliva samples
The participants were asked to collect their saliva samples between 6 AM and 12 PM by following the standard procedures described in the literature.,,, Eating, drinking, or oral rinsing were not allowed just before collecting saliva. A glass of water was given for rinsing 10 min before collecting saliva and then they were made to spit the saliva into a sterile container. A minimum of 5 mL saliva was collected. Samples contaminated with blood were rejected. The date and time of collection were recorded and the samples were refrigerated (below -20°C) immediately.
Processing of saliva samples
Processing of the samples was also done following the standard procedures. Due to freezing, the saliva samples precipitated mucins. So on the day of assay, they were thawed and centrifuged at 2,600 × g for 15 min at 4°C. Centrifugation removes the mucins and other particulates, which may result in false readings. The samples were brought to room temperature before being added to the assay plate.
Testing for interleukin-6 and albumin levels
Enzyme-linked immunosorbent assay (ELISA) kit for human IL-6 was used to obtain IL-6 levels in the saliva samples. Albumin Agappe kit (Ernakulam, Kerala) done by bromocresol green (BCG) method was used to obtain the albumin levels.
The data were entered in Microsoft XL spreadsheet and analyzed using IBM Statistical Package for Social Sciences, version 20 (SPSS 20). Descriptive statistics were presented in terms of mean, standard deviation (SD), median, and quartile. The difference in albumin and IL-6 levels between the two groups was compared using the Mann–Whitney U test. P value of less than 0.05 was considered to be statistically significant.
| Results|| |
The mean value of IL-6 in Group 1 (healthy) was 15.06 (SD was 4.42) and in Group 2 (OSCC) was 192.15 (SD was 82.76). On comparing the two mean values, it was seen that there was a significant difference in the salivary IL-6 levels in patients with OSCC when compared to the healthy group [Table 1] and Graph 1 [Additional file 1]].
The mean value of albumin in Group 1 (healthy) was 0.28 (SD was 0.19) and in Group 2 (OSCC) was 0.82 (SD was 0.41). On comparing the two mean values, it was seen that there was a significant rise in the salivary levels of albumin in OSCC patients when compared to the healthy group [Graph 2 [Additional file 2]].
| Discussion|| |
A variety of salivary markers have been studied, analyzed, and were correlated with the development, progression, and outcome of OSCC. Many studies conducted previously reported a significant variation in results. This may have been due to several factors such as the limited number of participants and difference in the location of the tumor. The present study was conducted to know whether IL-6 and albumin levels in the saliva can be used as useful biomarkers for the early detection and progression of OSCC. The results showed a significant rise in the salivary IL-6 levels in patients with OSCC when compared to the healthy group.
There was also a significant rise in salivary levels of albumin in OSCC patients when compared to the healthy group.
Thus, this study shows that salivary IL-6 and albumin levels could be used as a useful biomarker in OSCC patients.
A study by Mahnaz Saheb Jamee et al. showed that there was a statistically significant rise in salivary interleukin 6 levels in patients with OSCC when compared to healthy individuals. There was also a rise in the salivary tumor necrosis factor, IL 1 and IL 8 in the case group when compared to the control group but it was not statistically significant.
In a study by Maie A.R., St. John et al. the salivary and serum levels of IL-6 and IL-8 were assessed. The results showed that IL-8 levels were higher in the saliva (P. 01) and IL-6 levels were higher in the serum of patients with OSCC (P. 01).
A study was conducted with 19 patients of type-1 and type-2 tongue and gum cancer (9 men and 10 women) and 20 control subjects (15 men and 5 women). IL-1, IL-6, IL-8, and osteopoitin levels in the saliva were assessed with ELISA test. The results showed that the salivary levels of IL-1 and IL-6 were elevated in cancer patients compared to the control group. There was no significant rise in the salivary level of IL-8 and osteopoitin.
Another study by Alexis et al. in the tongue of squamous cell carcinoma cases showed that IL-1α, IL-6, IL-8, vascular endothelial growth factor A (VEGF-a), and tumor necrosis factor alpha (TNF-α) levels in the saliva can detect the development and progression of tongue squamous cell carcinoma at an early stage, substantiating their utility as biomarkers for cancer screening and early detection.
There are many advantages of using the salivary levels of different cytokines as potential biomarkers of OSCC. They are noninvasive screening tools, easily available, and they do not depend on tumor's location. Sample collection is easy, inexpensive, and can be performed easily. The present screening methods and protocols of OSCC will receive a major boost if we can determine a proper salivary biomarker profile. The ability to detect premalignant lesions and conditions early, before they develop into invasive disease could help in the diagnosis and better management of squamous cell carcinoma, thus leading to better cure rates and survival rates.
Salivary biomarkers can also be used to detect recurrence, which is a major cause of mortality in OSCC patients. After treatment, regular monitoring of the patient's salivary cytokine levels can help in the early diagnosis of recurrence.
| Conclusion|| |
In this study, 60 subjects were taken. They were divided into two groups with 30 subjects in each group, comprising OSCC patients and healthy individuals, respectively. In both the groups, salivary IL-6 and albumin levels were assessed.
It was seen that there was a statistically significant rise of salivary IL-6 and albumin levels in OSCC subjects when compared to the healthy group.
Hence, in this study IL-6 and albumin levels in the saliva could be used as biomarkers for OSCC. More robust studies will be required to corroborate these findings and verify the possible association of salivary IL-6 and albumin in OSCC.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Riedel F, Zaiss I, Herzog D, Götte K, Naim R, Hörmann K. Serum levels of Interleukin-6 in patients with primary head and neck squamous cell carcinoma. Anticancer Res 2005;25:2761-6.
Byakodi R, Byakodi S, Hiremath S, Byakodi J, Adaki S, Marathe K, et al
. Oral cancer in India: An epidemiologic and clinical review. J Community Health 2012;37:316-9.
Sankaranarayanan R, Ramadas K, Thomas G, Muwonge R, Thara S, Mathew B, et al
.; Trivandrum Oral Cancer Screening Study Group. Effect of screening on oral cancer mortality in Kerala, India: A cluster-randomised controlled trial. Lancet 2005;365:1927-33.
Wang YF, Chang SY, Tai SK, Li WY, Wang LS. Clinical significance of interleukin-6 and interleukin-6 receptor expression in oral squamous cell carcinoma. Head Neck 2002;24:850-8.
Mankan AK, Lawless MW, Gray SG, Kelleher D, McManus R. NF-kappaB regulation: The nuclear response. J Cell Mol Med 2009;13:631-43.
Xu J, Wu HF, Ang ES, Yip K, Woloszyn M, Zheng MH, et al
. NF-kappaB modulators in osteolytic bone diseases. Cytokine Growth Factor Rev 2009;20:7-17.
Feghali CA, Wright TM. Cytokines in acute and chronic inflammation. Front Biosci 1997;2:12-26.
Lisa Cheng YS, Jordan L, Gorugantula LM, Schneiderman E, Chen HS, Rees T. Salivary Interleukin-6 and -8 in patients with oral cancer and patients with chronic oral inflammatory diseases. J Periodontal 2014;85:956-65.
Meurman JH, Rantonen P, Pajukoski H, Sulkava R. Salivary albumin and other constituents and their relation to oral and general health in the elderly. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;94:432-8.
St John MA, Li Y, Zhou X, Denny P, Ho CM, Montemagno C, et al
. Interleukin 6 and interleukin 8 as potential biomarkers for oral cavity and oropharyngeal squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 2004;130:929-35.
Gorugantula LM, Rees T, Plemons J, Chen HS, Cheng YS. Salivary basic fibroblast growth factor in patients with oral squamous cell carcinoma or oral lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114:215-22.
Cheng YS, Rees T, Jordan L, Oxford L, O'Brien J, Chen HS, et al
. Salivary endothelin-1 potential for detecting oral cancer in patients with oral lichen planus or oral cancer in remission. Oral Oncol 2011;47:1122-6.
Navazesh M. Methods for collecting saliva. Ann N
Y Acad Sci 1993;694:72-7.
Saheb Jamee M, Eslami M, AtarbashiMoghadam F, Sarafnejad A. Salivary concentration of TNFalpha, IL1 alpha, IL6, and IL8 in oral squamous cell carcinoma. Med Oral Patol Oral Cir Bucal 2008;13:E292-5.
Katakura A, Kamiyama I, Takano N, Shibahara T, Muramatsu T, Ishihara K, et al
. Comparison of salivary cytokine levels in oral cancer patients and healthy subjects. Bull Tokyo Dent Coll 2007;48:199-203.
Korostoff A, Reder L, Masood R, Sinha UK. The role of salivary cytokine biomarkers in tongue cancer invasion and mortality. Oral Oncol 2011;47:282-7.
Rusthoven K, Ballonoff A, Raben D, Chen C. Poor prognosis in patients with stage I and II oral tongue squamous cell carcinoma. Cancer 2008;112:345-51.
|This article has been cited by|
||Salivary IL-6 mRNA is a Robust Biomarker in Oral Squamous Cell Carcinoma
| ||Ildikó Judit Márton,József Horváth,Péter Lábiscsák,Bernadett Márkus,Balázs Dezso,Adrienn Szabó,Ildikó Tar,József Piffkó,Petra Jakus,József Barabás,Péter Barabás,Lajos Olasz,Zsanett Kövér,József Tozsér,János Sándor,Éva Csosz,Beáta Scholtz,Csongor Kiss |
| ||Journal of Clinical Medicine. 2019; 8(11): 1958 |
|[Pubmed] | [DOI]|
||Polymicrobial interactions of
and its role in oral carcinogenesis
| ||Mohd Hafiz Arzmi,Stuart Dashper,Michael McCullough |
| ||Journal of Oral Pathology & Medicine. 2019; 48(7): 546 |
|[Pubmed] | [DOI]|
||Evaluation of Serum and Salivary Interleukin-6 and Interleukin-8 Levels in Oral Squamous Cell Carcinoma Patients: Systematic Review and Meta-Analysis
| ||Farzad Rezaei,Hamid Reza Mozaffari,Jafar Tavasoli,Elisa Zavattaro,Mohammad Moslem Imani,Masoud Sadeghi |
| ||Journal of Interferon & Cytokine Research. 2019; |
|[Pubmed] | [DOI]|