Interleukin 6 and interleukin 8 as potential biomarkers for oral cavity and oropharyngeal squamous cell carcinoma.
BACKGROUND
Since morbidity and mortality rates due to oral cavity and oropharyngeal squamous cell carcinoma (OSCC) have improved little in the past 30 years, early detection or prevention of this disease is likely to be most effective. Using laser-capture microdissection, we have identified the expression of 2 cellular genes that are uniquely associated with OSCC: interleukin (IL) 6 and IL-8. These cytokines may contribute to the pathogenesis of this disease, and have been linked with increased tumor growth and metastasis.


OBJECTIVE
To investigate whether IL-6 and/or IL-8 could serve as informative biomarkers for OSCC in saliva and/or serum and to determine if there is a role for saliva as a diagnostic medium for OSCC.


METHODS
Patients with newly diagnosed T1 or T2 oral cavity or oropharyngeal histologically confirmed squamous cell carcinoma were recruited for the study. Age and sex-matched disease-free subjects were used as controls. Using quantitative real-time polymerase chain reaction analysis and enzyme-linked immunosorbent assay, we respectively assessed the expression of IL-6 and IL-8 in serum (controls, n = 32; patients with OSCC, n = 19) and saliva (controls, n = 32; patients with OSCC, n = 32) at the messenger RNA (mRNA) and protein levels.


METHODS
Specificity and sensitivity of these biomarkers for OSCC and their predictive value.


RESULTS
Interleukin 8 was detected at higher concentrations in saliva (P<.01) and IL-6 was detected at higher concentrations in serum of patients with OSCC (P<.01). We confirmed these results at both the mRNA and the protein levels, and the results were concordant. The concentration of IL-8 in saliva and IL-6 in serum did not appear to be associated with sex, age, or alcohol or tobacco use (P>.75). Using statistical analysis, we were able to determine the threshold value, sensitivity, and specificity of each biomarker, as well as a combination of biomarkers, for detecting OSCC.


CONCLUSIONS
Our findings indicate that IL-8 in saliva and IL-6 in serum hold promise as biomarkers for OSCC. A saliva-based test could be a cost-effective adjunctive tool in the diagnosis and follow-up of patients with OSCC.
David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Maie A R
MA
St John
Yang
Y
Li
Xiaofeng
X
Zhou
Paul
P
Denny
Chih-Ming
CM
Ho
Carlo
C
Montemagno
Wenyuan
W
Shi
Fengxia
F
Qi
Benjamin
B
Wu
Uttam
U
Sinha
Richard
R
Jordan
Lawrence
L
Wolinsky
No-Hee
NH
Park
Honghu
H
Liu
Elliot
E
Abemayor
David T W
DT
Wong
D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002140:California; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism*; D016209:Interleukin-8 / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009055:Mouth / Q000378:metabolism* / Q000473:pathology*; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D009959:Oropharyngeal Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012463:Saliva / Q000737:chemistry / Q000378:metabolism; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger