title: Decreased expression of Kallmann syndrome 1 sequence gene (KAL1) contributes to oral squamous cell carcinoma progression and significantly correlates with poorly differentiated grade.
abstract: BACKGROUND
  Kallmann syndrome 1 sequence gene (KAL1) protein is an extracellular matrix associated protein which plays vital roles in neurons development and cell migration. However, its biological functions and clinical implications have yet not been revealed in oral carcinogenesis. The objective of the study was to evaluate the role of KAL1 in oral cancer and determine clinical significance of KAL1 in oral squamous cell carcinomas (OSCCs).
  
  
  METHODS
  The expression pattern of KAL1 was examined in a testing cohort including OSCCs (n = 42) and paired adjacent tissues (PATs) (n = 14) by real-time PCR. The result was further validated in a validating cohort of OSCCs (n = 32). Correlation between clinicopathological parameters and KAL1 mRNA levels was analyzed by Kruskal-Wallis test. In vitro, the effects of KAL1 ablation through siRNA-mediated knockdown on the proliferation of OSCC cells were determined by CCK-8, BrdU, and colonies formation assays, respectively. In addition, cell cycle distribution was further evaluated by cytometry.
  
  
  RESULTS
  We observed that remarkably decreased expression of KAL1 mRNA in two independent cohorts (P = 0.0002 and P = 0.033, respectively). Furthermore, downregulated KAL1 mRNA was significantly associated with worse pathological grade (P = 0.013 and P = 0.035, respectively). Upon KAL1 silencing, the proliferation and colonies formation potentials of OSCC cells were notably promoted by accelerating G1 to M phase transition.
  
  
  CONCLUSIONS
  These data indicated that KAL1 plays a potential suppressive role on OSCC initiation and progression, and KAL1 gene may serve as an adjuvant biomarker for the identification of pathological grade.
authors: Department of Oral Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Jiannan
authors: J
authors: Liu
authors: Wei
authors: W
authors: Cao
authors: Wantao
authors: W
authors: Chen
authors: Liqun
authors: L
authors: Xu
authors: Chenping
authors: C
authors: Zhang
mesh_terms: D001973:Bromodeoxyuridine; D063646:Carcinogenesis / Q000737:chemistry / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000473:pathology*; D018929:Cell Culture Techniques; D059447:Cell Cycle Checkpoints; D002454:Cell Differentiation; D002455:Cell Division; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015331:Cohort Studies; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000032:analysis* / Q000235:genetics; D005260:Female; D016193:G1 Phase; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000737:chemistry / Q000473:pathology; D009062:Mouth Neoplasms / Q000737:chemistry / Q000473:pathology*; D060787:Neoplasm Grading; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D012844:Sincalide; D025521:Tumor Suppressor Proteins / Q000032:analysis
chemical_list: C076266:ANOS1 protein, human; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D001973:Bromodeoxyuridine; D012844:Sincalide
keywords: KAL1; anosmin-1; biomarker; oral squamous cell carcinoma; suppressive role