Abstract
Carbonic anhydrase 9 (CAIX) is an important protein that stabilizes the extracellular pH value and is transcriptionally regulated by hypoxia-inducible factor 1 (HIF1), but more stable than HIF1α. Here we show a comparative study that examines the prognostic value of CA9 mRNA, CAIX protein of tumor cells and secreted CAIX protein for oral squamous cell carcinoma (OSCC) patients. Tumor samples from 72 OSCC patients and 24 samples of normal tissue were analyzed for CA9 mRNA levels. A total of 158 OSCC samples were stained for CAIX by immunohistochemistry and 89 blood serum samples were analyzed by ELISA for soluble CAIX protein content. Survival analyses were performed by Kaplan–Meier and Cox’s regression analysis to estimate the prognostic effect of CA9/CAIX in OSCC patients. The CA9 mRNA and CAIX protein levels of tumor cells correlated with each other, but not with those of the secreted CAIX protein level of the blood of patients. ROC curves showed a significant (p < 0.001) higher mRNA-level of CA9 in OSCC samples than in adjacent normal tissue. Cox’s regression analysis revealed an increased risk (i) of death for patients with a high CA9 mRNA level (RR = 2.2; p = 0.02), (ii) of locoregional recurrence (RR = 3.2; p = 0.036) at higher CA9 mRNA levels and (iii) of death at high CAIX protein level in their tumors (RR = 1.7; p = 0.066) and especially for patients with advanced T4-tumors (RR = 2.0; p = 0.04). However, the secreted CAIX protein level was only as a trend associated with prognosis in OSCC (RR = 2.2; p = 0.066). CA9/CAIX is an independent prognostic factor for OSCC patients and therefore a potential therapeutic target.
Highlights
Oral cancer is the 15th most common cancer worldwide [1]
The CA9 mRNA level in tumor tissue samples was significantly higher compared to tumor-associated normal tissue samples in this study cohort
MRNA level using datasets from The Cancer Genome Atlas (TCGA) of patients with oral cancer [35]. We found that those patients with a high tumor CA9 mRNA level (30% of all patients (n = 21)) had a significantly worse prognosis (Figure 2)
Summary
Oral cancer is the 15th most common cancer worldwide [1]. Oral squamous cell carcinoma (OSCC) is the major malignancy of all oral cancers [2,3]. The prognosis of OSCC has stagnated over the last decades [3]. New prognostic molecular parameters are needed to characterize the biology of OSCC and to enable an individual therapy concept. The history of determining additive prognostic parameters in OSCC dates back to 2003. Schliephake had analyzed the literature from five years (1997–2002) and included 169 articles in his review [4]. The complex field of tumor markers in OSCC has been classified into four groups according to their function:
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
