title: Differential BMI1, TWIST1, SNAI2 mRNA expression pattern correlation with malignancy type in a spectrum of common cutaneous malignancies: basal cell carcinoma, squamous cell carcinoma, and melanoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medical Genetics Department, School of Medicine, Tehran University of Medical Sciences, P.O. Box 14155-6447, Tehran, 14176-13151, Iran.
authors.forename: F
authors.initials: F
authors.lastname: Vand-Rajabpour
authors.affiliation: Medical Genetics Department, School of Medicine, Tehran University of Medical Sciences, P.O. Box 14155-6447, Tehran, 14176-13151, Iran.
authors.forename: N
authors.initials: N
authors.lastname: Sadeghipour
authors.affiliation: Dietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences, Karaj, Iran.
authors.forename: S
authors.initials: S
authors.lastname: Saee-Rad
authors.affiliation: Plastic, Reconstructive and Aesthetic Surgery Department, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.|Tumor Clinic, Pathology Department and the Department of Plastic and Reconstructive Surgery, Razi Dermatology Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: H
authors.initials: H
authors.lastname: Fathi
authors.affiliation: Tumor Clinic, Pathology Department and the Department of Plastic and Reconstructive Surgery, Razi Dermatology Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: P
authors.initials: P
authors.lastname: Noormohammadpour
authors.affiliation: Epidemiology and Biostatistics Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Yaseri
authors.affiliation: Tumor Clinic, Pathology Department and the Department of Plastic and Reconstructive Surgery, Razi Dermatology Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: K K
authors.initials: KK
authors.lastname: Hesari
authors.affiliation: Medical Genetics Department, School of Medicine, Tehran University of Medical Sciences, P.O. Box 14155-6447, Tehran, 14176-13151, Iran.
authors.forename: Z
authors.initials: Z
authors.lastname: Bagherpour
authors.affiliation: Medical Genetics Department, School of Medicine, Tehran University of Medical Sciences, P.O. Box 14155-6447, Tehran, 14176-13151, Iran. tabrizi@tums.ac.ir.
authors.forename: M
authors.initials: M
authors.lastname: Tabrizi
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002280:Basal Cell Carcinoma / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D063150:Polycomb Repressive Complex 1 / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D000071250:Snail Family Transcription Factors / Q000235:genetics*; D051879:Twist-Related Protein 1 / Q000235:genetics*
chemical_list: C069077:BMI1 protein, human; D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; D012333:RNA, Messenger; C000604408:SNAI2 protein, human; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D063150:Polycomb Repressive Complex 1
keywords: BMI1; Epithelial–mesenchymal transition; Metastasis; SNAI2/SLUG; Stemness; TWIST1