A robust and interpretable gene signature for predicting the lymph node status of primary T1/T2 oral cavity squamous cell carcinoma.

A robust and interpretable gene signature for predicting the lymph node status of primary T1/T2 oral cavity squamous cell carcinoma.
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DOI:
10.1002/ijc.33828
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发表时间:
2022-02-01
影响因子:
6.4
通讯作者:
Izumchenko E
Izumchenko E
中科院分区:
医学1区
文献类型:
--
作者:
Ghantous Y;Omar M;Broner EC;Agrawal N;Pearson AT;Rosenberg AJ;Mishra V;Singh A;El-Naaj IA;Savage PA;Sidransky D;Marchionni L;Izumchenko E

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口腔鳞状细胞癌(OSCC)每年在美国影响超过30,000人,吸烟和饮酒是主要的风险因素。早期肿瘤的治疗通常包括手术切除,然后在某些情况下进行术后放疗。颈部淋巴结(LN)是局部转移的最常见部位,如果原发肿瘤厚度大于3.5 mm,则通常进行选择性颈淋巴结清扫术。然而,术后组织学检查经常显示,许多早期疾病患者的颈淋巴结转移呈阴性,迫切需要改进风险分层,以避免过度治疗或防止疾病进展。为此,我们的目的是确定一个原发性肿瘤基因的签名,可以准确地预测颈部淋巴结转移的早期口腔鳞癌患者。使用来自189个样本的基因表达谱,我们训练了K-top评分对(K-TSP)模型,并确定了6个可以区分有淋巴结转移的原发性肿瘤与无转移的原发性肿瘤的基因对。使用RT-PCR在35名患者的独立队列中进一步验证了签名,其中其分别实现了90%和91%的ROC曲线下面积(AUC)和准确度。这些结果表明,这样的签名有希望作为一种快速和成本效益的方法,用于检测患者在发展颈部淋巴结转移的高风险,并可能用于指导颈部治疗方案在早期口腔鳞癌。
Oral cavity squamous cell carcinoma (OSCC) affects more than 30,000 individuals in the US annually, with smoking and alcohol consumption being the main risk factors. Management of early stage tumors usually includes surgical resection followed by postoperative radiotherapy in certain cases. The cervical lymph nodes (LN) are the most common site for local metastasis and elective neck dissection is usually performed if the primary tumor thickness is greater than 3.5 mm. However, postoperative histological examination often reveals that many patients with early stage disease are negative for neck nodal metastasis, posing a pressing need for improved risk stratification to either avoid over-treatment or prevent the disease progression. To this end, we aimed to identify a primary tumor gene signature that can accurately predict cervical LN metastasis in patients with early stage OSCC. Using gene expression profiles from 189 samples, we trained K-top scoring pairs (K-TSPs) models and identified six gene pairs that can distinguish primary tumors with nodal metastasis from those without metastasis. The signature was further validated on an independent cohort of 35 patients using RT-PCR in which it achieved an Area Under the ROC Curve (AUC) and accuracy of 90% and 91% respectively. These results indicate that such signature holds promise as a quick and cost effective method for detecting patients at high risk of developing cervical LN metastasis, and may be potentially used to guide the neck treatment regimen in early-stages OSCC.
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