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白细胞介素6和白细胞介素8作为口腔和口咽鳞状细胞癌的潜在生物标志物。

Interleukin 6 and interleukin 8 as potential biomarkers for oral cavity and oropharyngeal squamous cell carcinoma.

作者信息

St John Maie A R, Li Yang, Zhou Xiaofeng, Denny Paul, Ho Chih-Ming, Montemagno Carlo, Shi Wenyuan, Qi Fengxia, Wu Benjamin, Sinha Uttam, Jordan Richard, Wolinsky Lawrence, Park No-Hee, Liu Honghu, Abemayor Elliot, Wong David T W

机构信息

David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

出版信息

Arch Otolaryngol Head Neck Surg. 2004 Aug;130(8):929-35. doi: 10.1001/archotol.130.8.929.

Abstract

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.

OBJECTIVES

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.

PATIENTS AND 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.

MAIN OUTCOME MEASURES

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.

摘要

背景

由于口腔和口咽鳞状细胞癌(OSCC)的发病率和死亡率在过去30年中改善甚微,早期检测或预防这种疾病可能最为有效。通过激光捕获显微切割技术,我们已鉴定出2种与OSCC独特相关的细胞基因的表达:白细胞介素(IL)-6和IL-8。这些细胞因子可能促成这种疾病的发病机制,并与肿瘤生长和转移增加有关。

目的

研究IL-6和/或IL-8是否可作为OSCC在唾液和/或血清中的信息性生物标志物,并确定唾液作为OSCC诊断介质是否有作用。

患者与方法

招募新诊断为T1或T2期口腔或口咽组织学确诊鳞状细胞癌的患者进行研究。年龄和性别匹配的无病受试者用作对照。使用定量实时聚合酶链反应分析和酶联免疫吸附测定,我们分别在信使核糖核酸(mRNA)和蛋白质水平评估血清(对照,n = 32;OSCC患者,n = 19)和唾液(对照,n = 32;OSCC患者,n = 32)中IL-6和IL-8的表达。

主要观察指标

这些生物标志物对OSCC的特异性和敏感性及其预测价值。

结果

在OSCC患者的唾液中检测到较高浓度的白细胞介素8(P<0.01),在血清中检测到较高浓度的IL-6(P<0.01)。我们在mRNA和蛋白质水平均证实了这些结果,且结果一致。唾液中IL-8的浓度和血清中IL-6的浓度似乎与性别、年龄或饮酒或吸烟无关(P>0.75)。通过统计分析,我们能够确定每种生物标志物以及生物标志物组合检测OSCC的阈值、敏感性和特异性。

结论

我们的研究结果表明,唾液中的IL-8和血清中的IL-6有望作为OSCC的生物标志物。基于唾液的检测可能是OSCC患者诊断和随访中一种具有成本效益的辅助工具。

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