Sawant Sharada, Gokulan Ravindran, Dongre Harsh, Vaidya Milind, Chaukar Devendra, Prabhash Kumar, Ingle Arvind, Joshi Shriya, Dange Prerana, Joshi Shreyas, Singh Archana Kumari, Makani Vidhi, Sharma Shilpi, Jeyaram Ashok, Kane Shubhada, D'Cruz Anil
Vaidya Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410 210, Maharashtra, India.
Department of Oral Biology and Biomedical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
Clin Oral Investig. 2016 Jan;20(1):43-56. doi: 10.1007/s00784-015-1476-6. Epub 2015 Apr 28.
In the present study, we have investigated the prognostic value of known stem cell-associated molecules such as Oct4, CD44 and c-Myc in patients with oral SCC who had received post-surgery radio- and/or chemotherapy.
Immunohistochemistry was performed to analyse the expression of Oct4, CD44 and c-Myc in 87 tumour tissues, and the expression profile obtained was correlated with clinicopathological parameters of the patients with oral cancer. Tumourigenic potential of these molecules was also evaluated by in vivo studies.
Our results showed significant correlation of Oct4 (OS, p = 0.003; DFS, p = 0.001) and c-Myc (OS, p = 0.01; DFS, p = 0.03) with overall survival and disease-free survival independently. Furthermore, all the three markers in combinations of two markers each, i.e. Oct4 + CD44 (OS, p = 0.003; DFS, p = 0.001), Oct4 + c-Myc (OS, p = 0.0001; DFS, p = 0.0001), CD44 + c-Myc (OS, p = 0.008; DFS, p = 0.02) and in combinations of three markers each, i.e. Oct4 + CD44 + c-Myc (OS, p = 0.0001; DFS, p = 0.0001) also significantly correlated with overall survival and disease-free survival. Univariate and multivariate analyses further established the independent prognostic value of Oct4. Oct4-, CD44- and c-Myc-enriched populations independently induced sarcomatoid carcinomas whereas primary keratinocytes developed poorly differentiated carcinomas in immunodeficient mice.
Oct4 and c-Myc independently as well as in combination with CD44 might be useful for the prediction of local recurrence and poor survival of patients with oral cancer which is the novel finding of this study.
Oct4, c-Myc and CD44 can be used to predict local recurrence and the outcome of treatment in oral cancer patients. In addition, these molecules may find use as molecular targets for effective therapy.
在本研究中，我们调查了已知的干细胞相关分子如Oct4、CD44和c-Myc在接受手术后放疗和/或化疗的口腔鳞状细胞癌患者中的预后价值。
采用免疫组织化学方法分析87例肿瘤组织中Oct4、CD44和c-Myc的表达情况，并将所得表达谱与口腔癌患者的临床病理参数进行关联分析。还通过体内研究评估了这些分子的致瘤潜力。
我们的结果显示，Oct4（总生存期，p = 0.003；无病生存期，p = 0.001）和c-Myc（总生存期，p = 0.01；无病生存期，p = 0.03）与总生存期和无病生存期独立显著相关。此外，所有这三个标志物两两组合，即Oct4 + CD44（总生存期，p = 0.003；无病生存期，p = 0.001）、Oct4 + c-Myc（总生存期，p = 0.0001；无病生存期，p = 0.0001）、CD44 + c-Myc（总生存期，p = 0.008；无病生存期，p = 0.02）以及三个标志物组合，即Oct4 + CD44 + c-Myc（总生存期，p = 0.0001；无病生存期，p = 0.0001）也与总生存期和无病生存期显著相关。单因素和多因素分析进一步证实了Oct4的独立预后价值。富含Oct4、CD44和c-Myc的细胞群体分别独立诱导出肉瘤样癌，而原代表皮细胞在免疫缺陷小鼠中形成低分化癌。
Oct4和c-Myc单独以及与CD44联合可能有助于预测口腔癌患者的局部复发和不良生存，这是本研究的新发现。
Oct4、c-Myc和CD44可用于预测口腔癌患者的局部复发和治疗结果。此外，这些分子可能作为有效治疗的分子靶点。
