LTBP2 is a prognostic marker in head and neck squamous cell carcinoma

Abstract

Latent transforming growth factor (TGF)-beta binding protein 2 (LTBP2) belongs to the fibrillin/LTBP extracellular matrix glycoprotein superfamily. It plays vital roles in tumorigenesis through regulating TGFβ activity, elastogenesis and maintenance of the extracellular matrix (ECM) structure. In this study, we determined the expression levels of LTBP2 mRNA and protein in head and neck squamous cell carcinoma (HNSCC) tissues and adjacent normal tissues by quantitative reverse transcription PCR (qRT-PCR) and tissue microarray immunohistochemistry analysis (TMA-IHC) respectively. LTBP2 protein levels in cancer tissues were correlated with HNSCC patients' clinical characteristics and overall survival. Both LTBP2 mRNA and protein levels were significantly higher in HNSCC tissues than in adjacent normal tissues. High LTBP2 protein level was associated with lymph node metastasis and higher pTNM stages. High LTBP2 protein level is an independent prognostic marker in HNSCC. Our data suggest that LTBP2 acts as an oncogene in HNSCC development and progression. Detection of LTBP2 expression could be a useful prognosis marker and targeting LTBP2 may represent a novel strategy for cancer treatment through regulating activities of TGFβ.

Keywords: LTBP2; head and neck squamous cell carcinoma; immunohistochemistry; prognosis; qPCR.

Figure 1. LTBP2 mRNA level was significantly higher in HNSCC tissues than in adjacent normal tissues

LTBP2 mRNA was determined by qRT-PCR and relative quantification analysis by normalizing to GAPDH mRNA.

Figure 2. LTBP2 protein was detected in HNSCC tissues but not in adjacent normal tissues

LTBP2 protein was determined by TMA-IHC, a1–a2) HNSCC tissue, positive for LTBP2 protein expression; b1–b2) adjacent normal tissue, negative for LTBP2 protein expression. a1 and b1 are ×40 magnification (bar = 500 μm), a2 and b2 are ×400 magnification (bar = 50 μm). Red arrows indicate positive LTBP2 protein expression on cancerous epithelial cytoplasm, and green arrows indicate negative LTBP2 protein expression on adjacent normal tissue.

Figure 3. Survival curves of HNSCC patients by the Kaplan–Meier method and the log-rank test

(A) LTBP2+ HNSCC patients (green line, 1) had significantly worse overall survival than LTBP- patients (blue line, 0). (B) HNSCC patients with lymph node metastasis (green line, 1) had significantly worse overall survival than patients without lymph node metastasis (blue line, 0).