Hypermethylation of collagen α2 (I) gene (COL1A2) is an independent predictor of survival in head and neck cancer.
OBJECTIVE
Collagen production plays a role in the development of tumors from cancer cells. The aim of the present study is to examine the involvement of epigenetic alteration of Collagen α2 (I) (COL1A2) gene expression in cases of head and neck squamous cell carcinoma (HNSCC).


METHODS
COL1A2 expression was examined in a panel of cell lines using RT-PCR. The methylation status of the COL1A2 promoter was studied using bisulfate sequencing and methylation-specific PCR (MSP).


RESULTS
COL1A2 expression was absent in 6 of 11 (54.5%) UM-SCC cell lines, whereas three nonmalignant cell lines had stable expressions. MSP analysis showed that 46/98 (46.9%) contained methylated alleles. COL1A2 methylation was significantly correlated with tumor size (P = 0.041), lymph node status (P = 0.008), tumor stage (P = 0.011), H-cadherin methylation (P = 0.039) and disease-free survival (P = 0.005). On multivariate Cox proportional hazard regression, which included age, sex, smoking status, and alcohol exposure, both tumor stage and COL1A2 methylation remained independent prognostic factors.


CONCLUSIONS
This study suggests that CpG hypermethylation is a likely mechanism of COL1A2 gene inactivation, supporting the hypothesis that the COL1A2 gene may play a role in the tumorigenesis of HNSCC and may serve as an important biomarker.
Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan. kiyoshim@hamamed.ac.jp
Kiyoshi
K
Misawa
Takeharu
T
Kanazawa
Yuki
Y
Misawa
Atsushi
A
Imai
Shiori
S
Endo
Katsura
K
Hakamada
Hiroyuki
H
Mineta
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D002460:Cell Line; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D015820:Cadherins; D024042:Collagen Type I