PMID- 32178572 OWN - NLM STAT- MEDLINE DCOM- 20210416 LR - 20210416 IS - 1557-8534 (Electronic) IS - 1547-3287 (Linking) VI - 29 IP - 12 DP - 2020 Jun 15 TI - LY6D as a Chemoresistance Marker Gene and Therapeutic Target for Laryngeal Squamous Cell Carcinoma. PG - 774-785 LID - 10.1089/scd.2019.0210 [doi] AB - 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. FAU - Wang, Jue AU - Wang J AD - Shanxi Key Laboratory of Otorhinolaryngology, Head and Neck Cancer, Taiyuan, Shanxi, China. AD - Department of Otolaryngology, Head & Neck Surgery, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China. AD - The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Taiyuan, Shanxi, China. FAU - Fan, Jiamin AU - Fan J AD - Department of Otolaryngology, Head & Neck Surgery, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China. FAU - Gao, Wei AU - Gao W AD - Shanxi Key Laboratory of Otorhinolaryngology, Head and Neck Cancer, Taiyuan, Shanxi, China. AD - Department of Otolaryngology, Head & Neck Surgery, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China. AD - The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Taiyuan, Shanxi, China. FAU - Wu, Yongyan AU - Wu Y AD - Shanxi Key Laboratory of Otorhinolaryngology, Head and Neck Cancer, Taiyuan, Shanxi, China. AD - Department of Otolaryngology, Head & Neck Surgery, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China. AD - The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Taiyuan, Shanxi, China. FAU - Zhao, Qinli AU - Zhao Q AD - Shanxi Key Laboratory of Otorhinolaryngology, Head and Neck Cancer, Taiyuan, Shanxi, China. AD - Department of Otolaryngology, Head & Neck Surgery, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China. AD - The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Taiyuan, Shanxi, China. FAU - Chen, Bo AU - Chen B AD - Shanxi Key Laboratory of Otorhinolaryngology, Head and Neck Cancer, Taiyuan, Shanxi, China. AD - Department of Otolaryngology, Head & Neck Surgery, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China. AD - The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Taiyuan, Shanxi, China. FAU - Ding, Yongxia AU - Ding Y AD - Shanxi Key Laboratory of Otorhinolaryngology, Head and Neck Cancer, Taiyuan, Shanxi, China. AD - Department of Otolaryngology, Head & Neck Surgery, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China. FAU - Wen, Shuxin AU - Wen S AD - Department of Otolaryngology, Head & Neck Surgery, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China. FAU - Nan, Xinrong AU - Nan X AD - Department of Oral and Maxillofacial Surgery, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China. FAU - Wang, BinQuan AU - Wang B AD - Shanxi Key Laboratory of Otorhinolaryngology, Head and Neck Cancer, Taiyuan, Shanxi, China. AD - Department of Otolaryngology, Head & Neck Surgery, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China. AD - The Key Scientific and Technological Innovation Platform for Precision Diagnosis and Treatment of Head and Neck Cancer, Taiyuan, Shanxi, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200427 PL - United States TA - Stem Cells Dev JT - Stem cells and development JID - 101197107 RN - 0 (Antigens, Ly) RN - 0 (Antineoplastic Agents) RN - 0 (Biomarkers, Tumor) RN - 0 (GPI-Linked Proteins) RN - 0 (Ly6d protein, mouse) RN - P88XT4IS4D (Paclitaxel) RN - Q20Q21Q62J (Cisplatin) RN - U3P01618RT (Fluorouracil) SB - IM MH - Animals MH - Antigens, Ly/*genetics/metabolism MH - Antineoplastic Agents/pharmacology/therapeutic use MH - Biomarkers, Tumor/*genetics/metabolism MH - Carcinoma, Squamous Cell/drug therapy/*genetics/metabolism MH - Cisplatin/pharmacology/therapeutic use MH - *Drug Resistance, Neoplasm MH - Female MH - Fluorouracil/pharmacology/therapeutic use MH - GPI-Linked Proteins/genetics/metabolism MH - Hep G2 Cells MH - Humans MH - Laryngeal Neoplasms/drug therapy/*genetics/metabolism MH - Mice MH - Mice, Inbred BALB C MH - Neoplastic Stem Cells/drug effects/metabolism MH - Paclitaxel/pharmacology/therapeutic use MH - Transcriptome OTO - NOTNLM OT - LY6D OT - cancer stem cells (CSCs) OT - chemoresistance OT - laryngeal squamous cell carcinoma (LSCC) OT - stemness OT - transcriptome sequencing EDAT- 2020/03/18 06:00 MHDA- 2021/04/17 06:00 CRDT- 2020/03/18 06:00 PHST- 2020/03/18 06:00 [pubmed] PHST- 2021/04/17 06:00 [medline] PHST- 2020/03/18 06:00 [entrez] AID - 10.1089/scd.2019.0210 [doi] PST - ppublish SO - Stem Cells Dev. 2020 Jun 15;29(12):774-785. doi: 10.1089/scd.2019.0210. Epub 2020 Apr 27.