YKT6, as a potential predictor of prognosis and immunotherapy response for oral squamous cell carcinoma, is related to cell invasion, metastasis, and CD8+ T cell infiltration

Oncoimmunology. 2021 Jun 23;10(1):1938890. doi: 10.1080/2162402X.2021.1938890.

Abstract

Metastasis and immune suppression account for the poor prognosis of oral squamous cell carcinoma (OSCC). YKT6 is a member of the soluble NSF attachment protein receptor (SNARE) family, and the effect of YKT6 in OSCC remains elusive. The purpose of this study was to explore promising prognostic and immune therapeutic candidate biomarkers for OSCC and to understand the expression pattern, prognostic value, immune effects, and biological functions of YKT6. Genes correlated with tumor metastasis and CD8 + T cell levels were identified by weighted gene coexpression network analysis (WGCNA). Next, YKT6 was analyzed through differential expression, prognostic and machine learning analyses. The molecular and immune characteristics of YKT6 were analyzed in independent cohorts, clinical specimens, and in vitro. In addition, we investigated the role of YKT6 at the pan-cancer level. The results suggested that the red module in WGCNA, as a hub module, was associated with lymph node (LN) metastasis and CD8 + T cell infiltration. Upregulation of YKT6 was found in OSCC and linked to adverse prognosis. A nomogram model containing YKT6 expression and tumor stage was constructed for clinical practice. The aggressive and immune-inhibitory phenotypes showed YKT6 overexpression, and the effect of YKT6 on OSCC cell invasion and metastasis in vitro was observed. Moreover, the low expression of YKT6 was correlated with high CD8 + T cell levels and potential immunotherapy response in OSCC. Similar results were found at the pan-cancer level. In total, YKT6 is a promising candidate biomarker for prognosis, molecular, and immune characteristics in OSCC.

Keywords: CD8+ T cell; Oral squamous cell carcinoma; YKT6; immunotherapy; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes
  • Head and Neck Neoplasms* / immunology
  • Head and Neck Neoplasms* / therapy
  • Humans
  • Immunotherapy
  • Prognosis
  • R-SNARE Proteins / genetics*
  • Squamous Cell Carcinoma of Head and Neck* / immunology
  • Squamous Cell Carcinoma of Head and Neck* / therapy

Substances

  • R-SNARE Proteins
  • YKT6 protein, human

Grants and funding

This work was supported by the National Natural Science Foundation of China under Grant Nos. 82071148; the National Key Research and Development Program of China under Grant Nos. 2016YFC1102705; the Natural science fund of Shandong Province under Grant Nos. ZR2020QH093; and the Shandong Provincial Key Laboratory of Immunohematology Open Research Program under Grant Nos. 2019XYKF006.