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Synaptonemal complex protein 3 is a prognostic marker in cervical cancer.

Cho H, Noh KH, Chung JY, Takikita M, Chung EJ, Kim BW, Hewitt SM, Kim TW, Kim JH - PLoS ONE (2014)

Bottom Line: Functional studies using NIH3T3 cells demonstrated that the C-terminal region of human SCP3 is important for AKT activation and its oncogenic potential.High expression of SCP3 was significantly associated with tumor stage (P = 0.002) and tumor grade (P<0.001), while SCP3 expression was positively associated with pAKT protein level in cervical neoplasias.Survival times for patients with cervical cancer overexpressing both SCP3 and pAKT (median, 134.0 months, n = 68) were significantly shorter than for patients with low expression of either SCP3 or pAKT (161.5 months, n = 108) as determined by multivariate analysis (P = 0.020).

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.

ABSTRACT
Synaptonemal complex protein 3 (SCP3), a member of Cor1 family, is up-regulated in various cancer cells; however, its oncogenic potential and clinical significance has not yet been characterized. In the present study, we investigated the oncogenic role of SCP3 and its relationship with phosphorylated AKT (pAKT) in cervical neoplasias. The functional role of SCP3 expression was investigated by overexpression or knockdown of SCP3 in murine cell line NIH3T3 and human cervical cancer cell lines CUMC6, SiHa, CaSki, and HeLa both in vitro and in vivo. Furthermore, we examined SCP3 expression in tumor specimens from 181 cervical cancer and 400 cervical intraepithelial neoplasia (CIN) patients by immunohistochemistry and analyzed the correlation between SCP3 expression and clinicopathologic factors or survival. Overexpression of SCP3 promoted AKT-mediated tumorigenesis both in vitro and in vivo. Functional studies using NIH3T3 cells demonstrated that the C-terminal region of human SCP3 is important for AKT activation and its oncogenic potential. High expression of SCP3 was significantly associated with tumor stage (P = 0.002) and tumor grade (P<0.001), while SCP3 expression was positively associated with pAKT protein level in cervical neoplasias. Survival times for patients with cervical cancer overexpressing both SCP3 and pAKT (median, 134.0 months, n = 68) were significantly shorter than for patients with low expression of either SCP3 or pAKT (161.5 months, n = 108) as determined by multivariate analysis (P = 0.020). Our findings suggest that SCP3 plays an important role in the progression of cervical cancer through the AKT signaling pathway, supporting the possibility that SCP3 may be a promising novel cancer target for cervical cancer therapy.

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Kaplan-Meier plots for disease-free survival (A) and overall survival (B) according to SCP3 expression, combined SCP3 and pAKT expression, and pAKT expression alone.For patients with high SCP3 expression, the mean disease-free survival and overall survival were 122.4 months and 144.8 months (n = 108), respectively. For patients with low SCP3 expression, mean disease-free survival and overall survival were 153.5 months and 159.6 months (n = 68), respectively.
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pone-0098712-g006: Kaplan-Meier plots for disease-free survival (A) and overall survival (B) according to SCP3 expression, combined SCP3 and pAKT expression, and pAKT expression alone.For patients with high SCP3 expression, the mean disease-free survival and overall survival were 122.4 months and 144.8 months (n = 108), respectively. For patients with low SCP3 expression, mean disease-free survival and overall survival were 153.5 months and 159.6 months (n = 68), respectively.

Mentions: To investigate the clinical relevance of SCP3, we examined the effect of SCP3 expression on patient outcomes. Five-year disease-free survival and overall survival were analyzed through Kaplan-Meier plots as shown in Figure 6A and B. In survival analysis of SCP3, there were 33 cases of recurrences, 2 cases of persistent disease, and 18 deaths in the 108 patients with high expression of SCP3, whereas low expression of SCP3 (68 patients) was associated with 4 cases of recurrence and 2 deaths over a mean follow-up period of 56.32 months. Patients with high SCP3 expression displayed shorter disease-free survival (mean of 122.4 versus 153.5 months, P = 0.001) and overall survival (mean of 144.8 versus 159.6 months, P = 0.024) compared with that of patients with low expression of SCP3 (Figure 6A and 6B). Furthermore, patients with combined high SCP3 and high pAKT exhibited significantly worse disease-free survival (mean of 106.7 versus 160.3 months, P<0.001) and overall survival (P = 0.009) compared with the combined low SCP3 and low pAKT group. Interestingly, there were no deaths in combined low SCP3 and low pAKT patients (n = 37). We next examined the independent prognostic significance of SCP3 alone and high SCP3 combined with high pAKT, as well as other clinicopathological parameters, using the Cox proportional hazards model. According to multivariate analysis, FIGO stage was a significant risk factor for overall survival (P = 0.013), whereas lymph node metastasis remained a significant risk factor for disease-free survival (P = 0.024) (Table 2). High SCP3 expression was a risk factor for recurrence [hazard ratio = 5.52 (95% CI, 1.78–17.11), P = 0.003], whereas high pAKT expression was a risk factor for disease-free survival [hazard ratio = 3.62 (95% CI, 1.19–11.05), P = 0.023] and overall survival [hazard ratio = 3.60 (95% CI, 1.04–12.42), P = 0.043]. Notably, the combination of high SCP3 and high pAKT expression was a significant risk factor for both disease free survival [hazard ratio = 4.98 (95% CI, 1.90–13.01), P = 0.001] and overall survival [hazard ratio = 3.38 (95% CI, 1.21–9.43), P = 0.020].


Synaptonemal complex protein 3 is a prognostic marker in cervical cancer.

Cho H, Noh KH, Chung JY, Takikita M, Chung EJ, Kim BW, Hewitt SM, Kim TW, Kim JH - PLoS ONE (2014)

Kaplan-Meier plots for disease-free survival (A) and overall survival (B) according to SCP3 expression, combined SCP3 and pAKT expression, and pAKT expression alone.For patients with high SCP3 expression, the mean disease-free survival and overall survival were 122.4 months and 144.8 months (n = 108), respectively. For patients with low SCP3 expression, mean disease-free survival and overall survival were 153.5 months and 159.6 months (n = 68), respectively.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4048308&req=5

pone-0098712-g006: Kaplan-Meier plots for disease-free survival (A) and overall survival (B) according to SCP3 expression, combined SCP3 and pAKT expression, and pAKT expression alone.For patients with high SCP3 expression, the mean disease-free survival and overall survival were 122.4 months and 144.8 months (n = 108), respectively. For patients with low SCP3 expression, mean disease-free survival and overall survival were 153.5 months and 159.6 months (n = 68), respectively.
Mentions: To investigate the clinical relevance of SCP3, we examined the effect of SCP3 expression on patient outcomes. Five-year disease-free survival and overall survival were analyzed through Kaplan-Meier plots as shown in Figure 6A and B. In survival analysis of SCP3, there were 33 cases of recurrences, 2 cases of persistent disease, and 18 deaths in the 108 patients with high expression of SCP3, whereas low expression of SCP3 (68 patients) was associated with 4 cases of recurrence and 2 deaths over a mean follow-up period of 56.32 months. Patients with high SCP3 expression displayed shorter disease-free survival (mean of 122.4 versus 153.5 months, P = 0.001) and overall survival (mean of 144.8 versus 159.6 months, P = 0.024) compared with that of patients with low expression of SCP3 (Figure 6A and 6B). Furthermore, patients with combined high SCP3 and high pAKT exhibited significantly worse disease-free survival (mean of 106.7 versus 160.3 months, P<0.001) and overall survival (P = 0.009) compared with the combined low SCP3 and low pAKT group. Interestingly, there were no deaths in combined low SCP3 and low pAKT patients (n = 37). We next examined the independent prognostic significance of SCP3 alone and high SCP3 combined with high pAKT, as well as other clinicopathological parameters, using the Cox proportional hazards model. According to multivariate analysis, FIGO stage was a significant risk factor for overall survival (P = 0.013), whereas lymph node metastasis remained a significant risk factor for disease-free survival (P = 0.024) (Table 2). High SCP3 expression was a risk factor for recurrence [hazard ratio = 5.52 (95% CI, 1.78–17.11), P = 0.003], whereas high pAKT expression was a risk factor for disease-free survival [hazard ratio = 3.62 (95% CI, 1.19–11.05), P = 0.023] and overall survival [hazard ratio = 3.60 (95% CI, 1.04–12.42), P = 0.043]. Notably, the combination of high SCP3 and high pAKT expression was a significant risk factor for both disease free survival [hazard ratio = 4.98 (95% CI, 1.90–13.01), P = 0.001] and overall survival [hazard ratio = 3.38 (95% CI, 1.21–9.43), P = 0.020].

Bottom Line: Functional studies using NIH3T3 cells demonstrated that the C-terminal region of human SCP3 is important for AKT activation and its oncogenic potential.High expression of SCP3 was significantly associated with tumor stage (P = 0.002) and tumor grade (P<0.001), while SCP3 expression was positively associated with pAKT protein level in cervical neoplasias.Survival times for patients with cervical cancer overexpressing both SCP3 and pAKT (median, 134.0 months, n = 68) were significantly shorter than for patients with low expression of either SCP3 or pAKT (161.5 months, n = 108) as determined by multivariate analysis (P = 0.020).

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.

ABSTRACT
Synaptonemal complex protein 3 (SCP3), a member of Cor1 family, is up-regulated in various cancer cells; however, its oncogenic potential and clinical significance has not yet been characterized. In the present study, we investigated the oncogenic role of SCP3 and its relationship with phosphorylated AKT (pAKT) in cervical neoplasias. The functional role of SCP3 expression was investigated by overexpression or knockdown of SCP3 in murine cell line NIH3T3 and human cervical cancer cell lines CUMC6, SiHa, CaSki, and HeLa both in vitro and in vivo. Furthermore, we examined SCP3 expression in tumor specimens from 181 cervical cancer and 400 cervical intraepithelial neoplasia (CIN) patients by immunohistochemistry and analyzed the correlation between SCP3 expression and clinicopathologic factors or survival. Overexpression of SCP3 promoted AKT-mediated tumorigenesis both in vitro and in vivo. Functional studies using NIH3T3 cells demonstrated that the C-terminal region of human SCP3 is important for AKT activation and its oncogenic potential. High expression of SCP3 was significantly associated with tumor stage (P = 0.002) and tumor grade (P<0.001), while SCP3 expression was positively associated with pAKT protein level in cervical neoplasias. Survival times for patients with cervical cancer overexpressing both SCP3 and pAKT (median, 134.0 months, n = 68) were significantly shorter than for patients with low expression of either SCP3 or pAKT (161.5 months, n = 108) as determined by multivariate analysis (P = 0.020). Our findings suggest that SCP3 plays an important role in the progression of cervical cancer through the AKT signaling pathway, supporting the possibility that SCP3 may be a promising novel cancer target for cervical cancer therapy.

Show MeSH
Related in: MedlinePlus