LY6D as a Chemoresistance Marker Gene and Therapeutic Target for Laryngeal Squamous Cell Carcinoma

Stem Cells Dev. 2020 Jun 15;29(12):774-785. doi: 10.1089/scd.2019.0210. Epub 2020 Apr 27.

Abstract

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.

Keywords: LY6D; cancer stem cells (CSCs); chemoresistance; laryngeal squamous cell carcinoma (LSCC); stemness; transcriptome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Ly / genetics*
  • Antigens, Ly / metabolism
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use
  • Drug Resistance, Neoplasm*
  • Female
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Hep G2 Cells
  • Humans
  • Laryngeal Neoplasms / drug therapy
  • Laryngeal Neoplasms / genetics*
  • Laryngeal Neoplasms / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism
  • Paclitaxel / pharmacology
  • Paclitaxel / therapeutic use
  • Transcriptome

Substances

  • Antigens, Ly
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • GPI-Linked Proteins
  • Ly6d protein, mouse
  • Paclitaxel
  • Cisplatin
  • Fluorouracil