Objective This work aims to investigate the expression pattern and clinicopathologic significance of centromere protein H(CENP-H) in uterine cervical cancer(UCC). Methods The level of CENP-H expression in the paraffin...Objective This work aims to investigate the expression pattern and clinicopathologic significance of centromere protein H(CENP-H) in uterine cervical cancer(UCC). Methods The level of CENP-H expression in the paraffin sections of 62 UCC cases was determined by the SP immunohistochemical method,with complete clinicopathologic data in all cases.Statistical analysis was conducted to evaluate the prognostic and diagnostic significance of CENP-H using SPSS13.0 software package. Results Immunohistochemical assay showed strong CENP-H expression in 61.29% (38/62) of the paraffin-embedded cervical cancer tissues.Statistical analysis revealed a strong correlation between the CENP-H expression and the clinical classification(P=0.038) of the cervical carcinoma.The expression increased with rise of the stages.The analysis of Cox proportional hazards regression model suggested that CENP-H expression(P=0.002) and tumor stage(P=0.001) were independent prognostic markers for the survival of UCC patients.The survival analysis showed that the survival rate was significantly lower in patients with high expression of CENP-H than in those with low expression of CENP-H(P=0.001). Conclusions CENP-H is likely to be a valuable marker for carcinogenesis and progression of UCC.It might be used as the important diagnostic and prognostic marker for cervical carcinoma patients,especially for those at early stage.展开更多
Kinetochores are large proteinaceous structure on the surface of chromosomes’ primary constriction during mitosis. They link chromosomes to spindle microtubules and also regulate the spindle assem- bly checkpoint, wh...Kinetochores are large proteinaceous structure on the surface of chromosomes’ primary constriction during mitosis. They link chromosomes to spindle microtubules and also regulate the spindle assem- bly checkpoint, which is crucial for correct chromosome segregation in all eukaryotes. The better known core networks of kinetochores include the KMN network (K, KNL1; M, Mis12 complex; N, Ndc80 complex)and CCAN (constitutive centromere-associated network). However, the detailed molecular mechanism of the kinetochore protein network remains unclear. This study demonstrates that CENP-H and CENP-K form quite stable subcomplex by TAP (tandem affinity purification) with HEK 293 cells which express TAP-CENP-K, with the ratio of purified CENP-H and CENP-K being close to 1︰1 even with high salt. Bioinformatic analysis suggests that CENP-H and CENP-K are enriched with coiled-coil regions. This implies that CENP-H and CENP-K form heterodimeric coiled-coils. Furthermore, the func- tional regions which form the complex are respectively located on their N- and C-terminals, but the association between the C-terminals is more complex. It is possible that this is the first identified het- erodimeric coiled-coils within the inner kinetochore, which is directly involved in the attachment be- tween kinetochores and the spindle microtubules.展开更多
Breast cancer is one of the leading causes of cancer death worldwide.This study aimed to analyze the expression of centromere protein H(CENP-H) in breast cancer and to correlate it with clinicopathologic data,includin...Breast cancer is one of the leading causes of cancer death worldwide.This study aimed to analyze the expression of centromere protein H(CENP-H) in breast cancer and to correlate it with clinicopathologic data,including patient survival.Using reverse transcription-polymerase chain reaction and Western blotting to detect the expression of CENP-H in normal mammary epithelial cells,immortalized mammary epithelial cell lines,and breast cancer cell lines,we observed that the mRNA and protein levels of CENP-H were higher in breast cancer cell lines and in immortalized mammary epithelial cells than in normal mammary epithelial cells.We next examined CENP-H expression in 307 paraffin-embedded archived samples of clinicopathologically characterized breast cancer using immunohistochemistry,and detected high CENP-H expression in 134(43.6%) samples.Statistical analysis showed that CENP-H expression was related with clinical stage(P = 0.001),T classification(P = 0.032),N classification(P = 0.018),and Ki-67(P < 0.001).Patients with high CENP-H expression had short overall survival.Multivariate analysis showed that CENP-H expression was an independent prognostic indicator for patient survival.Our results suggest that CENP-H protein is a valuable marker of breast cancer progression and prognosis.展开更多
基金supported by grants from the Social Development Projects of Guangdong SciTech Planning (No.2010B031600201)
文摘Objective This work aims to investigate the expression pattern and clinicopathologic significance of centromere protein H(CENP-H) in uterine cervical cancer(UCC). Methods The level of CENP-H expression in the paraffin sections of 62 UCC cases was determined by the SP immunohistochemical method,with complete clinicopathologic data in all cases.Statistical analysis was conducted to evaluate the prognostic and diagnostic significance of CENP-H using SPSS13.0 software package. Results Immunohistochemical assay showed strong CENP-H expression in 61.29% (38/62) of the paraffin-embedded cervical cancer tissues.Statistical analysis revealed a strong correlation between the CENP-H expression and the clinical classification(P=0.038) of the cervical carcinoma.The expression increased with rise of the stages.The analysis of Cox proportional hazards regression model suggested that CENP-H expression(P=0.002) and tumor stage(P=0.001) were independent prognostic markers for the survival of UCC patients.The survival analysis showed that the survival rate was significantly lower in patients with high expression of CENP-H than in those with low expression of CENP-H(P=0.001). Conclusions CENP-H is likely to be a valuable marker for carcinogenesis and progression of UCC.It might be used as the important diagnostic and prognostic marker for cervical carcinoma patients,especially for those at early stage.
基金Supported by the National Key Scientific Program (Grant No. 2006CB910100).
文摘Kinetochores are large proteinaceous structure on the surface of chromosomes’ primary constriction during mitosis. They link chromosomes to spindle microtubules and also regulate the spindle assem- bly checkpoint, which is crucial for correct chromosome segregation in all eukaryotes. The better known core networks of kinetochores include the KMN network (K, KNL1; M, Mis12 complex; N, Ndc80 complex)and CCAN (constitutive centromere-associated network). However, the detailed molecular mechanism of the kinetochore protein network remains unclear. This study demonstrates that CENP-H and CENP-K form quite stable subcomplex by TAP (tandem affinity purification) with HEK 293 cells which express TAP-CENP-K, with the ratio of purified CENP-H and CENP-K being close to 1︰1 even with high salt. Bioinformatic analysis suggests that CENP-H and CENP-K are enriched with coiled-coil regions. This implies that CENP-H and CENP-K form heterodimeric coiled-coils. Furthermore, the func- tional regions which form the complex are respectively located on their N- and C-terminals, but the association between the C-terminals is more complex. It is possible that this is the first identified het- erodimeric coiled-coils within the inner kinetochore, which is directly involved in the attachment be- tween kinetochores and the spindle microtubules.
文摘Breast cancer is one of the leading causes of cancer death worldwide.This study aimed to analyze the expression of centromere protein H(CENP-H) in breast cancer and to correlate it with clinicopathologic data,including patient survival.Using reverse transcription-polymerase chain reaction and Western blotting to detect the expression of CENP-H in normal mammary epithelial cells,immortalized mammary epithelial cell lines,and breast cancer cell lines,we observed that the mRNA and protein levels of CENP-H were higher in breast cancer cell lines and in immortalized mammary epithelial cells than in normal mammary epithelial cells.We next examined CENP-H expression in 307 paraffin-embedded archived samples of clinicopathologically characterized breast cancer using immunohistochemistry,and detected high CENP-H expression in 134(43.6%) samples.Statistical analysis showed that CENP-H expression was related with clinical stage(P = 0.001),T classification(P = 0.032),N classification(P = 0.018),and Ki-67(P < 0.001).Patients with high CENP-H expression had short overall survival.Multivariate analysis showed that CENP-H expression was an independent prognostic indicator for patient survival.Our results suggest that CENP-H protein is a valuable marker of breast cancer progression and prognosis.
