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SOX4 expression is associated with treatment failure and chemoradioresistance in oral squamous cell carcinoma.

Yoon TM, Kim SA, Cho WS, Lee DH, Lee JK, Park YL, Lee KH, Lee JH, Kweon SS, Chung IJ, Lim SC, Joo YE - BMC Cancer (2015)

Bottom Line: 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.It could be a potential prognostic marker for OSCC.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Kaplan–Meier curves of overall survival (OS) and disease specific survival (DSS) for patients with oral squamous cell carcinoma (OSCC) by SOX4 expression. a SOX4 expression significantly correlated with diminished OS and DSS in patients with OSCC (n = 85, P = 0.036 and P = 0.007, respectively). b SOX4 expression was associated with significantly worse OS and DSS in patients with OSCC, who were treated with chemotherapy and/or radiotherapy (n = 50, P = 0.007 and P = 0.003, respectively). Solid line: patients with low SOX4 expression; dotted line: patients with high SOX4 expression
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Fig5: Kaplan–Meier curves of overall survival (OS) and disease specific survival (DSS) for patients with oral squamous cell carcinoma (OSCC) by SOX4 expression. a SOX4 expression significantly correlated with diminished OS and DSS in patients with OSCC (n = 85, P = 0.036 and P = 0.007, respectively). b SOX4 expression was associated with significantly worse OS and DSS in patients with OSCC, who were treated with chemotherapy and/or radiotherapy (n = 50, P = 0.007 and P = 0.003, respectively). Solid line: patients with low SOX4 expression; dotted line: patients with high SOX4 expression

Mentions: To study the prognostic role of SOX4 in OSCC, we investigated the correlation between SOX4 expression and clinicopathological factors. SOX4 expression in OSCC was not associated with age, sex, location, T stage (tumor invasion), N stage or lymph node metastasis (P > 0.05, Table 1). However, SOX4 expression was correlated with recurrence (P = 0.004) and treatment failure (P = 0.032; Table 1). Moreover, overall survival (OS) and diease specific survival (DSS) of patients with high SOX4 expression was significantly shorter than for those with low SOX4 expression (P = 0.036 and P = 0.007, respectively; Fig. 5a). In 50 patients who were treated with chemotherapy and/or radiotherapy, patients with high SOX4 expression had significantly shorter OS and DSS than those with low SOX4 expression (P = 0.007 and P = 0.003, respectively; Fig. 5b).Fig. 5


SOX4 expression is associated with treatment failure and chemoradioresistance in oral squamous cell carcinoma.

Yoon TM, Kim SA, Cho WS, Lee DH, Lee JK, Park YL, Lee KH, Lee JH, Kweon SS, Chung IJ, Lim SC, Joo YE - BMC Cancer (2015)

Kaplan–Meier curves of overall survival (OS) and disease specific survival (DSS) for patients with oral squamous cell carcinoma (OSCC) by SOX4 expression. a SOX4 expression significantly correlated with diminished OS and DSS in patients with OSCC (n = 85, P = 0.036 and P = 0.007, respectively). b SOX4 expression was associated with significantly worse OS and DSS in patients with OSCC, who were treated with chemotherapy and/or radiotherapy (n = 50, P = 0.007 and P = 0.003, respectively). Solid line: patients with low SOX4 expression; dotted line: patients with high SOX4 expression
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4641419&req=5

Fig5: Kaplan–Meier curves of overall survival (OS) and disease specific survival (DSS) for patients with oral squamous cell carcinoma (OSCC) by SOX4 expression. a SOX4 expression significantly correlated with diminished OS and DSS in patients with OSCC (n = 85, P = 0.036 and P = 0.007, respectively). b SOX4 expression was associated with significantly worse OS and DSS in patients with OSCC, who were treated with chemotherapy and/or radiotherapy (n = 50, P = 0.007 and P = 0.003, respectively). Solid line: patients with low SOX4 expression; dotted line: patients with high SOX4 expression
Mentions: To study the prognostic role of SOX4 in OSCC, we investigated the correlation between SOX4 expression and clinicopathological factors. SOX4 expression in OSCC was not associated with age, sex, location, T stage (tumor invasion), N stage or lymph node metastasis (P > 0.05, Table 1). However, SOX4 expression was correlated with recurrence (P = 0.004) and treatment failure (P = 0.032; Table 1). Moreover, overall survival (OS) and diease specific survival (DSS) of patients with high SOX4 expression was significantly shorter than for those with low SOX4 expression (P = 0.036 and P = 0.007, respectively; Fig. 5a). In 50 patients who were treated with chemotherapy and/or radiotherapy, patients with high SOX4 expression had significantly shorter OS and DSS than those with low SOX4 expression (P = 0.007 and P = 0.003, respectively; Fig. 5b).Fig. 5

Bottom Line: 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.It could be a potential prognostic marker for OSCC.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus