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缺氧诱导因子-1α(HIF-1α)C1772T 多态性是否可预测口腔鳞状细胞癌(OSCC)患者的短期预后?

Does Hypoxia-Inducible Factor -1 α (HIF-1α) C1772T polymorphism predict short-term prognosis in patients with oral squamous cell carcinoma (OSCC)?

机构信息

All India Institute of Medical Sciences, New Delhi, India.

Maulana Azad Medical College and associated hospitals, New Delhi, India.

出版信息

J Oral Pathol Med. 2018 Aug;47(7):660-664. doi: 10.1111/jop.12718. Epub 2018 May 16.

Abstract

BACKGROUND

Oral squamous cell carcinoma (OSCC) is a cancer of the oral cavity that is a major health problem in India. There is an urgent need to identify biomarkers that have prognostic significance. We studied HIF-1α levels as well as single-nucleotide polymorphism of HIF-1α gene in cancer and healthy controls.

METHODS

Fifty newly diagnosed OSCC patients and 50 age and sex-matched healthy control were included in the study. Serum concentrations of HIF-1α were measured by sandwich ELISA; whereas HIF-1α gene polymorphism study was performed using restriction enzyme digestion by HpH I.

RESULTS

The major genotype observed was CC genotype in both control (84%) and patients (86%) followed by CT genotype (control 16%, cases 14%). CT genotype led to more aggressive tumors. On subgroup analysis based on prognosis, the median overall survival of patients who were treatment responders was 488 days (16.2 months) and that of the patients with progressive disease was 365 days (12.1 months). The patients who expired during the study observation period had median survival of 330 days (11 months).

CONCLUSION

Our study showed that CT genotype for C1772T polymorphism of HIF-1α predisposes to aggressive tumor phenotype in patients with OSCC. Moreover, patients with CT genotype had poor survival rate as compared to CC genotype. A cut-off value of 460 pg/mL of HIF-1α can help to segregate patients with OSCC from healthy controls.

摘要

背景

口腔鳞状细胞癌(OSCC)是一种口腔癌症,在印度是一个主要的健康问题。迫切需要确定具有预后意义的生物标志物。我们研究了 HIF-1α 水平以及癌症和健康对照组中 HIF-1α 基因的单核苷酸多态性。

方法

本研究纳入了 50 名新诊断的 OSCC 患者和 50 名年龄和性别匹配的健康对照者。采用夹心 ELISA 法测定 HIF-1α 血清浓度;采用 HpH I 限制酶消化法进行 HIF-1α 基因多态性研究。

结果

在对照组(84%)和患者组(86%)中,主要基因型均为 CC 基因型,其次是 CT 基因型(对照组 16%,病例组 14%)。CT 基因型导致肿瘤更具侵袭性。基于预后的亚组分析,治疗反应者的总生存中位数为 488 天(16.2 个月),进展性疾病患者的总生存中位数为 365 天(12.1 个月)。在研究观察期间死亡的患者中位生存期为 330 天(11 个月)。

结论

本研究表明,HIF-1α 的 C1772T 多态性 CT 基因型使 OSCC 患者易发生侵袭性肿瘤表型。此外,与 CC 基因型相比,CT 基因型患者的生存率较差。HIF-1α 的 460pg/mL 截断值可有助于将 OSCC 患者与健康对照组区分开来。

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