Vand-Rajabpour F, Sadeghipour N, Saee-Rad S, Fathi H, Noormohammadpour P, Yaseri M, Hesari K K, Bagherpour Z, Tabrizi M
Medical Genetics Department, School of Medicine, Tehran University of Medical Sciences, P.O. Box 14155-6447, Tehran, 14176-13151, Iran.
Dietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences, Karaj, Iran.
Clin Transl Oncol. 2017 Apr;19(4):489-497. doi: 10.1007/s12094-016-1555-4. Epub 2016 Oct 7.
Melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) can be used as a unique model to identify molecular mechanisms to distinguish rarely metastatic (BCC), often metastatic (SCC) and most metastatic (melanoma) cancer. It is known that epithelial-mesenchymal transition and stemness transcription factors (TWIST1, SNAI2/SLUG, and BMI1) play an important role in metastasis and their dysregulation has been demonstrated in metastatic cancers. We hypothesized that this spectrum of cutaneous cancers (BCC, SCC, and melanoma) would be a unique cancer model system to elucidate steps toward cancer invasion and metastasis.
We evaluated the mRNA expression level of BMI1, TWIST1, and SNAI2/SLUG and studied clinicopathological features in 170 skin cancers along with normal tissue samples.
We demonstrate downregulation of BMI1 mRNA expression in BCC samples compared with controls (p = 0.0001), SCC (p = 0.001), and melanoma (p = 0.0001) samples. Downregulation of TWIST1 mRNA expression is seen in only BCC samples compared with controls (p = 0.031). High SNAI2 mRNA expression is represented in melanoma samples compared with controls (p = 0.022) and SCC samples (p = 0.031). High mRNA expression of TWIST1 is seen in patients with positive history of cancers. Extremely low mRNA expression of BMI1 is detected in patients with positive history of cancers other than skin cancer.
These findings provide support for the hypothesis that the spectrum of cutaneous cancers could be better understood as a series of gene dosage-dependent entities with distinct molecular events. Oncogene-induced senescence, mechanism of which is still unclear, could be one explanation for these results.
黑色素瘤、鳞状细胞癌（SCC）和基底细胞癌（BCC）可作为一种独特的模型，用于识别区分极少转移（BCC）、常转移（SCC）和最易转移（黑色素瘤）癌症的分子机制。已知上皮-间质转化和干性转录因子（TWIST1、SNAI2/SLUG和BMI1）在转移中起重要作用，且它们的失调在转移性癌症中已得到证实。我们假设，这种皮肤癌谱（BCC、SCC和黑色素瘤）将是阐明癌症侵袭和转移步骤的独特癌症模型系统。
我们评估了BMI1、TWIST1和SNAI2/SLUG的mRNA表达水平，并研究了170例皮肤癌以及正常组织样本的临床病理特征。
与对照（p = 0.0001）、SCC（p = 0.001）和黑色素瘤（p = 0.0001）样本相比，我们发现BCC样本中BMI1 mRNA表达下调。与对照相比，仅在BCC样本中观察到TWIST1 mRNA表达下调（p = 0.031）。与对照（p = 0.022）和SCC样本（p = 0.031）相比，黑色素瘤样本中SNAI2 mRNA表达较高。癌症病史阳性的患者中可见TWIST1的高mRNA表达。除皮肤癌外，癌症病史阳性的患者中检测到BMI1的极低mRNA表达。
这些发现支持了这样一种假设，即皮肤癌谱可更好地理解为一系列具有不同分子事件的基因剂量依赖性实体。致癌基因诱导的衰老（其机制仍不清楚）可能是这些结果的一种解释。
