Overexpression of a disintegrin and metalloproteinase 9 (ADAM9) in relation to poor prognosis of patients with oral squamous cell carcinoma

Abstract

This study investigates the expressions of ADAM9, CDCP1 and t-PA in OSCC and their impacts on patient prognosis. Previous research has demonstrated the overexpression of ADAM9 and activation of plasminogen activator in OSCC, but CDCP1's role remains unexplored. While these biomolecules are known to contribute to lung cancer metastasis, their concurrent expressions in OSCC have not been thoroughly examined. Our aim is to assess the expressions of ADAM9, CDCP1, and t-PA in OSCC specimens, compare them with normal oral tissues, and explore their correlation with OSCC's clinicopathological features and patient survival outcomes.

Keywords: A disintegrin and metalloproteinase 9; CUB domain-containing protein 1; Oral squamous cell carcinoma; Overexpression; Tissue-type plasminogen activato.

Fig. 1

Representative immunohistochemical images of various staining intensities, including weak, moderate, and intense for ADAM9, CDCP1, and t-PA expressions in normal oral tissues and in different histopathological diagnoses, including well, moderately, and poorly differentiated oral squamous cell carcinoma (OSCC) tissues. Bars = 50 μm

Fig. 2

Correlation of ADAM9, CDCP1, and t-PA expression and histopathological differentiation, as well as overall survival in OSCC. (A) A bar graph comparing the mean immunoreactive scores (IRS) of ADAM9, CDCP1, and t-PA between 63 OSCC (gray) and 12 normal (black) tissues, expressed as mean ± SD (error bars); Statistical analysis was performed using unpaired student’s t test, *P < 0.05 ****P < 0.0001. (B) The correlations between the IRS of ADAM9, CDCP1, or t-PA and the distinct degrees of histopathological differentiation, including 28 well differentiated OSCC, 24 moderately differentiated OSCC, 11 poorly differentiated OSCC, and 12 normal tissues. A horizontal line in each box represents a median with the interquartile range. (C) The correlations between each pair of the IRS for ADAM9, CDCP1, and t-PA. A horizontal line in each box represents a median with the interquartile range; an empty circle represents an outlier; an asterisk represents an extreme value. (D) The cutoff values for the three biomolecules, including ADAM9, CDCP1, and t-PA, were estimated from the time-dependent receiver operating characteristic (ROC) curves of their IRS. (E) The Kaplan–Meier overall survival analysis for 63 patients with OSCC according to the high (gray) and the low (black) IRS of ADAM9, CDCP1, and t-PA during a 4-year follow-up period. Overall survival is defined as a period between the date of surgery and the date of death or the end of research project