Increased Expression of LAMTOR5 Predicts Poor Prognosis and Is Associated with Lymph Node Metastasis of Head and Neck Squamous Cell Carcinoma

Int J Med Sci. 2019 Jun 2;16(6):783-792. doi: 10.7150/ijms.33415. eCollection 2019.

Abstract

Late endosomal/lysosomal adaptor and MAPK and mTOR activator 5 (LAMTOR5) is a novel oncoprotein associated with several human malignancies, but its clinical role in head and neck squamous cell carcinoma (HNSCC) remains unclear. The present study aims to investigate the clinical and pathological significance of LAMTOR5 in HNSCC. We utilized immunohistochemical staining of human tissue microarrays (210 primary HNSCC, 42 normal oral mucosae, 69 oral epithelial dysplasia, and 68 metastasis lymph nodes) to explore the clinical and pathological significance of LAMTOR5 in HNSCC. Additionally, expression level of LAMTOR5 in immunoreactivity of Pten conditional knock out (Pten cKO) mice HNSCC was also assessed. We found LAMTOR5 was overexpressed in human and Pten cKO mice HNSCC, and its expression was significantly associated with patients' overall survival, lymph node metastasis and lymph node grade. Furthermore, LAMTOR5 expression was significantly correlated with the expression of p-AktSer473, p-S6Ser235/236, immune checkpoints (PD-L1, Galectin 9, VISTA and B7-H4) and macrophage markers (CD68 and CD163). In Pten cKO mice HNSCC, it was also significantly correlated with VISTA and F4/80. Consequently, we consider that high expression of LAMTOR5 might be a poor prognostic indicator and correlated with the immunosuppression of tumor microenvironment.

Keywords: LAMTOR5; head and neck squamous cell carcinoma; immunohistochemistry; knockout mice; prognosis.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Biomarkers, Tumor / metabolism*
  • Disease Models, Animal
  • Female
  • Follow-Up Studies
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Kaplan-Meier Estimate
  • Lymph Nodes / pathology
  • Lymphatic Metastasis / pathology*
  • Male
  • Mice, Knockout
  • Mouth Mucosa / pathology
  • Mouth Mucosa / surgery
  • PTEN Phosphohydrolase / genetics
  • Prognosis
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / mortality
  • Squamous Cell Carcinoma of Head and Neck / pathology*
  • Tissue Array Analysis

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • LAMTOR5 protein, human
  • Lamtor5 protein, mouse
  • PTEN Phosphohydrolase
  • Pten protein, mouse