title: SOX4 expression is associated with treatment failure and chemoradioresistance in oral squamous cell carcinoma.
abstract: BACKGROUND
  In humans, sex-determining region-Y (SRY) related high-mobility-group box 4 (SOX4) is linked to development and tumorigenesis. SOX4 is over-expressed in several cancers and has prognostic significance. This study evaluated whether SOX4 affects oncogenic behavior and chemoradiotherapy response in head and neck squamous cell carcinoma (HNSCC) cells, and documented the relationship between its expression and prognosis in oral squamous cell carcinoma (OSCC).
  
  
  METHODS
  We used small interfering RNA in HNSCC cells to evaluate the effect of SOX4 on cell proliferation, apoptosis, chemoradiation-induced apoptosis, invasion, and migration. SOX4 expression in OSCC tissues was investigated by immunohistochemistry.
  
  
  RESULTS
  SOX4 knockdown (KO) decreased cell proliferation and induced apoptosis by activating caspases-3 and -7, and poly-ADP ribose polymerase and suppressing X-linked inhibitor of apoptosis protein in HNSCC cells; it also enhanced radiation/cisplatin-induced apoptosis; and suppressed tumor cell invasion and migration. Immunostaining showed SOX4 protein was significantly increased in OSCC tissues compared with adjacent normal mucosa. SOX4 expression was observed in 51.8 % of 85 OSCC tissues, and was significantly correlated with treatment failure (P = 0.032) and shorter overall survival (P = 0.036) in patients with OSCC.
  
  
  CONCLUSIONS
  SOX4 may contribute to oncogenic phenotypes of HNSCC cells by promoting cell survival and causing chemoradioresistance. It could be a potential prognostic marker for OSCC.
authors.affiliation: Departments of Otorhinolaryngology-Head and Neck Surgery, Chonnam National University Medical School and Hwasun Hospital, 8 Hak-Dong, Dong-Ku, Gwangju, 501-757, South Korea. yoontm@chonnam.ac.kr.
authors.forename: Tae Mi
authors.initials: TM
authors.lastname: Yoon
authors.affiliation: Departments of Otorhinolaryngology-Head and Neck Surgery, Chonnam National University Medical School and Hwasun Hospital, 8 Hak-Dong, Dong-Ku, Gwangju, 501-757, South Korea. annie0215@naver.com.
authors.forename: Sun-Ae
authors.initials: SA
authors.lastname: Kim
authors.affiliation: Departments of Otorhinolaryngology-Head and Neck Surgery, Chonnam National University Medical School and Hwasun Hospital, 8 Hak-Dong, Dong-Ku, Gwangju, 501-757, South Korea. ggangnet@hanmail.net.
authors.forename: Wan Seok
authors.initials: WS
authors.lastname: Cho
authors.affiliation: Departments of Otorhinolaryngology-Head and Neck Surgery, Chonnam National University Medical School and Hwasun Hospital, 8 Hak-Dong, Dong-Ku, Gwangju, 501-757, South Korea. lee3l@hanmail.net.
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Departments of Otorhinolaryngology-Head and Neck Surgery, Chonnam National University Medical School and Hwasun Hospital, 8 Hak-Dong, Dong-Ku, Gwangju, 501-757, South Korea. joonkyoo@chonnam.ac.kr.
authors.forename: Joon Kyoo
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Departments of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, 8 Hak-Dong, Dong-Ku, Gwangju, 501-757, South Korea. kokodeak@hanmail.net.
authors.forename: Young-Lan
authors.initials: YL
authors.lastname: Park
authors.affiliation: Departments of Pathology, Chonnam National University Medical School and Hwasun Hospital, 8 Hak-Dong, Dong-Ku, Gwangju, 501-757, South Korea. mdkaylee@gmail.com.
authors.forename: Kyung-Hwa
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Departments of Pathology, Chonnam National University Medical School and Hwasun Hospital, 8 Hak-Dong, Dong-Ku, Gwangju, 501-757, South Korea. jhlee@chonnam.ac.kr.
authors.forename: Jae Hyuk
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Departments of Preventive Medicine, Chonnam National University Medical School and Hwasun Hospital, 8 Hak-Dong, Dong-Ku, Gwangju, 501-757, South Korea. ujingogo@paran.com.
authors.forename: Sun-Seog
authors.initials: SS
authors.lastname: Kweon
authors.affiliation: Departments of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, 8 Hak-Dong, Dong-Ku, Gwangju, 501-757, South Korea. ijchung@chonnam.ac.kr.
authors.forename: Ik-Joo
authors.initials: IJ
authors.lastname: Chung
authors.affiliation: Departments of Otorhinolaryngology-Head and Neck Surgery, Chonnam National University Medical School and Hwasun Hospital, 8 Hak-Dong, Dong-Ku, Gwangju, 501-757, South Korea. limsc@chonnama.ac.kr.
authors.forename: Sang Chul
authors.initials: SC
authors.lastname: Lim
authors.affiliation: Departments of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, 8 Hak-Dong, Dong-Ku, Gwangju, 501-757, South Korea. yejoo@chonnam.ac.kr.
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Joo
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D011379:Prognosis; D011836:Radiation Tolerance / Q000235:genetics; D055751:SOXC Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck; D017211:Treatment Failure
chemical_list: D014408:Biomarkers, Tumor; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors