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LY6D as a Chemoresistance Marker Gene and Therapeutic Target for Laryngeal Squamous Cell Carcinoma.
Stem Cells and Development ( IF 4 ) Pub Date : 2020-06-11 , DOI: 10.1089/scd.2019.0210
Jue Wang 1, 2, 3 , Jiamin Fan 2 , Wei Gao 1, 2, 3 , Yongyan Wu 1, 2, 3 , Qinli Zhao 1, 2, 3 , Bo Chen 1, 2, 3 , Yongxia Ding 1, 2 , Shuxin Wen 2 , Xinrong Nan 4 , BinQuan Wang 1, 2, 3
Affiliation  

Laryngeal squamous cell carcinoma (LSCC) is a common head and neck cancer that is unresponsive to chemotherapy; therefore, understanding the causes of chemotherapy resistance is important. The cancer stem cell (CSC) theory postulates that CSCs are the source of tumor chemoresistance. We enrich laryngeal CSCs to overcome chemoresistance of LSCC. A laryngeal cancer xenograft model was established, and a low dose of cisplatin was administered until chemoresistance arose. A next-generation xenograft model was established using surviving tumor cells, and the test was repeated four times to screen for CSCs. Cell function experiments were performed on each tumor cell generation (m1, m2, m3, and m4). The m3 line, with the highest stemness, was selected for transcriptome sequencing. LY6D was selected for clinical sample validation and functional verification. LY6D expression was detected in 107 laryngeal cancer samples, with high expression in 91 of these samples. LY6D expression was correlated with pathological T and clinical stages, and with cervical lymph node metastasis. The siLY6D group exhibited reduced adhesion and chemoresistance to cisplatin, 5-fluorouracil, and paclitaxel. LY6D is upregulated in laryngeal cancer and may serve as a biomarker for chemoresistance in CSCs. Moreover, LY6D could serve as an alternative antigenic peptide in the targeted treatment of laryngeal cancer.

中文翻译:

LY6D作为化学抗性标记基因和喉鳞状细胞癌的治疗靶标。

喉鳞状细胞癌(LSCC)是常见的头颈癌,对化疗无反应;因此,了解化疗耐药的原因很重要。癌症干细胞(CSC)理论假定CSC是肿瘤化学耐药性的来源。我们丰富了喉CSC,以克服LSCC的化学耐药性。建立了喉癌异种移植模型,并给予低剂量的顺铂直至产生化学耐药性。使用存活的肿瘤细胞建立了下一代异种移植模型,并且重复进行了四次测试以筛选CSC。对每个肿瘤细胞世代(m1,m2,m3和m4)进行细胞功能实验。选择干度最高的m3系进行转录组测序。LY6D选择用于临床样品验证和功能验证。在107个喉癌样本中检测到LY6D表达,其中91个样本高表达。LY6D的表达与病理T和临床分期以及宫颈淋巴结转移有关。si LY6D组对顺铂,5-氟尿嘧啶和紫杉醇的粘附力和化学抗性降低。LY6D在喉癌中表达上调,可作为CSC中化学耐药性的生物标记。此外,LY6D可以作为喉癌靶向治疗中的替代抗原肽。
更新日期:2020-06-11
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