循环肿瘤细胞的分子谱分析可预测头颈部鳞状细胞癌的临床结局。

Molecular profiling of circulating tumor cells predicts clinical outcome in head and neck squamous cell carcinoma.

机构信息

Department of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma 3718511, Japan.

出版信息

Oral Oncol. 2020 Mar;102:104558. doi: 10.1016/j.oraloncology.2019.104558. Epub 2020 Feb 7.

DOI:10.1016/j.oraloncology.2019.104558

PMID:32044652

Abstract

OBJECTIVES

The relationship between the molecular profiling of circulating tumor cells (CTCs) and clinical factors is a challenge. In this study, we performed molecular detection and characterization of CTCs in patients with head and neck squamous cell carcinoma (HNSCC).

MATERIALS AND METHODS

CTCs captured by microfilter were analyzed for the expression of multiple epithelial markers (EPCAM, MET, KRT19, and EGFR) by RT-qPCR. The CTCs-positive samples were further analyzed for the expression of 10 genes (PIK3CA, CCND1, SNAI1, VIM, CD44, NANOG, ALDH1A1, CD47, CD274, and PDCD1LG2). Finally, we analyzed whether the molecular profiling of CTCs was associated with clinical factors.

RESULTS

Twenty-eight (63.6%) of the 44 HNSCC patients were positive for at least one epithelial-related gene. CTC-positivity was significantly correlated with treatment resistance (p = 0.0363), locoregional recurrence (p = 0.0151), and a shorter progression-free survival (PFS) (p = 0.0107). Moreover, the expression of MET in CTCs was associated with a shorter PFS (p = 0.0426). Notably, patients with CD274-positive CTC showed prolonged PFS (p = 0.0346) and overall survival (p = 0.0378) compared to those with CD274-negative CTC.

CONCLUSION

Our results suggest that molecular profiling characterized by the gene expression of CTCs influences clinical factors in patients with HNSCC.

摘要

目的

循环肿瘤细胞（CTC）的分子谱与临床因素之间的关系是一个挑战。在本研究中，我们对头颈部鳞状细胞癌（HNSCC）患者的 CTC 进行了分子检测和特征分析。

材料与方法

通过微滤器捕获的 CTCs 通过 RT-qPCR 分析多种上皮标志物（EPCAM、MET、KRT19 和 EGFR）的表达。对 CTC 阳性样本进一步分析 10 个基因（PIK3CA、CCND1、SNAI1、VIM、CD44、NANOG、ALDH1A1、CD47、CD274 和 PDCD1LG2）的表达。最后，我们分析了 CTC 的分子谱是否与临床因素相关。

结果

44 例 HNSCC 患者中有 28 例（63.6%）至少有一种上皮相关基因呈阳性。CTC 阳性与治疗耐药（p=0.0363）、局部区域复发（p=0.0151）和较短的无进展生存期（PFS）（p=0.0107）显著相关。此外，CTC 中 MET 的表达与较短的 PFS 相关（p=0.0426）。值得注意的是，与 CD274 阴性 CTC 相比，CD274 阳性 CTC 患者的 PFS（p=0.0346）和总生存期（p=0.0378）更长。