Gene-expression profiles of primary and metastatic lesions in head and neck squamous cell carcinoma. Gene-expression profiles of primary and metastatic lesions in head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of malignancies arising from different sites and the 8th most common type of cancer in the world. While the advent of new techniques and multimodality therapy have improved prognosis of locally HNSCC, the appearance of distant metastases (DM) remains a challenge both for prognosis and treatment. To date, the genomic landscape of dissemination of HNSCC has to be further studied, in order to predict whether a patient will develop distant metastases. Therefore, knowing that the risk of disease spread to DM is directly correlated to initial staging, it suggested the hypothesis that the development of DM could be linked to the biologic characteristics of the primary tumor. The aim of our work is to compare gene expression profile of primary tumors of patients who develop and not develop DM. Additionally, we studied the expression profile of matched distant metastasis. Overall design: We identified and matched histologically confirmed primary tumor of 49 HNSCC patients, divided in 24 without metastasis (“T-without”) and 25 with distant metastasis (“T-with”), collected from 2006 to 2016. In 23 of the 25 selected T-with cases, we collected matched FFPE samples of the distant metastasis (M). The following criteria have been used to match T-with versus T-without based on clinical and radiological staging: i) cT1 has been matched with cT1 or cT2 and viceversa for staged cT2 tumors; ii) cT3 has been matched with cT3 or cT4 and viceversa for cT4; iii) cN1 has been matched with cN0 or cN1; cN2 has been matched with cN3 and viceversa for cN3. T-with and T-without were well balanced per age, sex and previous radiotherapy performed in the curative setting on the head and neck area. Among T-with patients, the majority had lung metachronous metastases.

头颈部鳞状细胞癌（HNSCC）是一类起源于不同解剖部位的异质性恶性肿瘤，也是全球范围内第八大常见癌症类型。尽管新技术与多模式治疗的出现改善了局部HNSCC的预后，但远处转移（DM）的发生仍是预后评估与临床治疗面临的难题。截至目前，HNSCC播散的基因组特征仍有待进一步研究，以精准预测患者是否会发生远处转移。鉴于疾病发生远处转移的风险与初始临床分期直接相关，我们提出假说：远处转移的发生可能与原发肿瘤的生物学特性存在关联。本研究旨在对比发生远处转移与未发生远处转移患者的原发肿瘤基因表达谱；此外，我们还对匹配的远处转移灶的表达谱进行了分析。总体实验设计：我们筛选并匹配了49例经组织学确认的HNSCC患者的原发肿瘤样本，其中24例无转移（命名为"T-without"组），25例伴远处转移（命名为"T-with"组），样本采集时间跨度为2006年至2016年。在25例T-with组患者中，我们获取了其中23例患者的匹配远处转移灶福尔马林固定石蜡包埋（FFPE）样本（命名为"M"组）。我们基于临床与影像学分期对T-with组与T-without组进行匹配，匹配标准如下：i）cT1期患者与cT1或cT2期患者匹配，cT2期患者反之亦然；ii）cT3期患者与cT3或cT4期患者匹配，cT4期患者反之亦然；iii）cN1期患者与cN0或cN1期患者匹配；cN2期患者与cN3期患者匹配，反之亦然。两组患者在年龄、性别以及头颈部区域根治性放疗史方面均保持均衡。在T-with组患者中，多数患者的远处转移为肺异时性转移灶。