Increased expression of carbonic anhydrase IX in oral submucous fibrosis and oral squamous cell carcinoma.
BACKGROUND
Cumulative evidence has demonstrated that carbonic anhydrase IX (CAIX) is upregulated in many types of human cancers. We attempted to evaluate plasma levels of CAIX in patients with oral cancer and investigated whether plasma CAIX is correlated with the progression of this disease.


METHODS
In total, 191 patients with oral cancer, 30 patients with oral submucous fibrosis and 100 controls were recruited in this study. The plasma samples were collected and the levels of soluble CAIX in plasma were determined by the enzyme-linked immunosorbent assay (ELISA). Furthermore, the normal buccal mucosa fibroblast was challenged by arecoline, the major areca nut alkaloid, to assess the relationship between the levels of CAIX and areca nut chewing in oral cancer patients.


RESULTS
Results showed that patients with oral cancer exhibited significantly higher levels of soluble CAIX compared to controls (p<0.001). Plasma levels of CAIX in oral cancer patients were associated with clinical stages after adjusting for age and areca nut chewing (p<0.05). In addition, patients with areca nuts chewing had higher CAIX levels than those who have not chewed areca nuts. Total carbonic anhydrase activity and CAIX mRNA levels were significantly higher in oral submucous fibrosis fibroblasts than in normal buccal mucosa fibroblasts. Moreover, arecoline elevated CAIX expression in a dose-dependent manner in normal buccal mucosa fibroblasts.


CONCLUSIONS
Our results suggest that determining plasma levels of CAIX may be used as a non-invasive method for monitoring oral cancer progression and the involvement of areca quid chewing in oral carcinogenesis may be related to a higher expression of CAIX.
Jia-Sin
JS
Yang
Mu-Kuan
MK
Chen
Shun-Fa
SF
Yang
Yu-Chao
YC
Chang
Shih-Chi
SC
Su
Hui-Ling
HL
Chiou
Ming-Hsien
MH
Chien
Chiao-Wen
CW
Lin
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D001114:Areca / Q000009:adverse effects; D001115:Arecoline / Q000009:adverse effects; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000187:drug effects / Q000201:enzymology; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D009914:Oral Submucous Fibrosis / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000951:Antigens, Neoplasm; D012333:RNA, Messenger; D001115:Arecoline; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases