Overexpression of KITLG predicts unfavorable clinical outcomes and promotes lymph node metastasis via the JAK/STAT pathway in nasopharyngeal carcinoma

Lab Invest. 2022 Nov;102(11):1257-1267. doi: 10.1038/s41374-022-00817-4. Epub 2022 Jul 13.

Abstract

Lymph node metastasis (LNM) is an early clinical sign and a contributor to the treatment failure in patients with nasopharyngeal carcinoma (NPC). The molecular mechanisms of LNM in NPC remain unclear. We aimed to identify and validate the possible key genes that play a crucial role in the LNM of NPC. The study included a discovery and validation phase. In the discovery phase, the key gene was identified by bioinformatics analysis. In the validation phase, the mRNA and protein expression of the key gene was detected by RT-PCR in NPC cells and by immunohistochemistry in a tissue microarray. Then, the effect of the key gene expression on cell invasion and migration was explored in vitro and in vivo. As a result, KITLG was identified as the key gene. The overexpression of KITLG was detected in NPC cells, which was correlated with neck lymph node metastasis and poor prognosis in patients with NPC. The suppression of KITLG inhibited the proliferation, invasion, and metastasis of NPC cells in vitro and in vivo. JAK/STAT signaling pathway might mediate the enhancement of cell invasion and metastasis caused by KITLG. In summary, the overexpression of KITLG in NPC cells might play a crucial role in the LNM of NPC, raising the possibility of KITLG as a prognostic factor and a potential target for NPC treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Janus Kinases* / genetics
  • Janus Kinases* / metabolism
  • Lymphatic Metastasis
  • Nasopharyngeal Carcinoma / metabolism
  • Nasopharyngeal Neoplasms* / metabolism
  • Prognosis
  • RNA, Messenger
  • STAT Transcription Factors / metabolism
  • Signal Transduction / genetics

Substances

  • Janus Kinases
  • STAT Transcription Factors
  • RNA, Messenger