微型核醣核酸－149基因多型性與罹患口腔鱗狀細胞癌及其預後之相關性

The Relevance between the Single Nucleotide Polymorphism of MicroRNA-149 and the Susceptibility with Prognosis in Oral Squamous Cell Carcinoma

張哲綸(Che-Lun Chang) ； 涂曦丰(Hsi-Feng Tu) ； 高壽延(Shou-Yen Kao) ； 張國威(Kuo-Wei Chang) ； 劉崇基(Chung-Ji Liu)

《臺灣口腔顎面外科學會雜誌》 24卷4期 (2013/12) Pp. 229-242

摘要

MicroRNAs (miRNAs) are a group of non-coding single strand RNA molecule encompassing 19-23 nucleotides in length, which can regulate protein expressions. In literature review, it showed that the level of miR-149 was significantly down-regulated in oral squamous cell carcinoma (OSCC) tissue, and it implicated that miR-149 might be involved in OSCC carcinogenesis. Moreover, there is a common single nucleotide polymorphism (SNP) located on precursor of miR-149. By using direct sequencing, we analyzed 273 cases of oral cancer to confirm the relationship of SNP of miR-149 (rs2292832 C→T) with susceptibility, severity, and prognosis of OSCC. Comparing to controls, precancerous cases (oral submucous fibrosis; OSF) and OSCC, the result shows a gradually increasing percentage of miR-149 C/T, T/T genotype (p＜0.001), and also increasing frequency of T allelotype (p＜0.001). In OSCC cases, by using binary logistic regression analysis, T/T genotype has stronger correlation to late stage cancer (OR=1.989; p=0.011), to advanced primary tumor (OR=1.775; p=0.037), and to cervical nodal metastasis (OR=2.573; p=0.002) than C/C and C/T genotypes. Also, it reveals that miR-149 genotypes can be an independent factor for anticipating cervical nodal metastasis in OSCC cases (p=0.002). In survival analysis, T/T genotype has the worst outcome. (p=0.032). Furthermore, Cox regression analysis shows that the miR-149 T/T genotype has a hazard ratio of 1.632 comparing to genotype C/C and C/T. Aforementioned results indicate that miR-149 SNP is significantly associated with disease susceptibility, severity, and prognosis of OSCC.

關鍵字

口腔鱗狀上皮細胞癌 ； 疾病感受性 ； 預後 ； 微型核醣核酸－149 ； 基因多型性

並列摘要

MicroRNAs (miRNAs) are a group of non-coding single strand RNA molecule encompassing 19-23 nucleotides in length, which can regulate protein expressions. In literature review, it showed that the level of miR-149 was significantly down-regulated in oral squamous cell carcinoma (OSCC) tissue, and it implicated that miR-149 might be involved in OSCC carcinogenesis. Moreover, there is a common single nucleotide polymorphism (SNP) located on precursor of miR-149. By using direct sequencing, we analyzed 273 cases of oral cancer to confirm the relationship of SNP of miR-149 (rs2292832 C→T) with susceptibility, severity, and prognosis of OSCC. Comparing to controls, precancerous cases (oral submucous fibrosis; OSF) and OSCC, the result shows a gradually increasing percentage of miR-149 C/T, T/T genotype (p＜0.001), and also increasing frequency of T allelotype (p＜0.001). In OSCC cases, by using binary logistic regression analysis, T/T genotype has stronger correlation to late stage cancer (OR=1.989; p=0.011), to advanced primary tumor (OR=1.775; p=0.037), and to cervical nodal metastasis (OR=2.573; p=0.002) than C/C and C/T genotypes. Also, it reveals that miR-149 genotypes can be an independent factor for anticipating cervical nodal metastasis in OSCC cases (p=0.002). In survival analysis, T/T genotype has the worst outcome. (p=0.032). Furthermore, Cox regression analysis shows that the miR-149 T/T genotype has a hazard ratio of 1.632 comparing to genotype C/C and C/T. Aforementioned results indicate that miR-149 SNP is significantly associated with disease susceptibility, severity, and prognosis of OSCC.

並列關鍵字

oral squamous cell carcinoma ； OSCC ； susceptibility ； prognosis ； miR-149 ； single nucleotide polymorphism