Abstract
BackgroundMany kinetochore proteins have been shown to be associated with human cancers. The aim of the present study was to clarify the expression of Centromere protein H (CENP-H), one of the fundamental components of the human active kinetochore, in esophageal carcinoma and its correlation with clinicopathological features.MethodsWe examined the expression of CENP-H in immortalized esophageal epithelial cells as well as in esophageal carcinoma cells, and in 12 cases of esophageal carcinoma tissues and the paired normal esophageal tissues by RT-PCR and Western blot analysis. In addition, we analyzed CENP-H protein expression in 177 clinicopathologically characterized esophageal carcinoma cases by immunohistochemistry. Statistical analyses were applied to test for prognostic and diagnostic associations.ResultsThe level of CENP-H mRNA and protein were higher in the immortalized cells, cancer cell lines and most cancer tissues than in normal control tissues. Immunohistochemistry showed that CENP-H was expressed in 127 of 171 ESCC cases (74.3%) and in 3 of 6 esophageal adenocarcinoma cases (50%). Statistical analysis of ESCC cases showed that there was a significant difference of CENP-H expression in patients categorized according to gender (P = 0.013), stage (P = 0.023) and T classification (P = 0.019). Patients with lower CENP-H expression had longer overall survival time than those with higher CENP-H expression. Multivariate analysis suggested that CENP-H expression was an independent prognostic marker for esophageal carcinoma patients. A prognostic value of CENP-H was also found in the subgroup of T3~T4 and N0 tumor classification.ConclusionOur results suggest that CENP-H protein is a valuable marker of esophageal carcinoma progression. CENP-H might be used as a valuable prognostic marker for esophageal carcinoma patients.
Highlights
Many kinetochore proteins have been shown to be associated with human cancers
Expression of Centromere protein H (CENP-H) in esophageal carcinoma cell lines To investigate the expression levels of centromere protein (CENP)-H transcripts and protein in esophageal cancer cell lines, semiquantitative reverse transcription-PCR analysis and Western blotting analysis were done in NE-3, 108CA, Eca-109, TE-1, and Kyse140 cell lines
Western blotting analysis showed that CENP-H protein was highly expressed in all cell lines, whereas it was weakly detected in normal esophageal tissue (Fig. 1)
Summary
Many kinetochore proteins have been shown to be associated with human cancers. The aim of the present study was to clarify the expression of Centromere protein H (CENP-H), one of the fundamental components of the human active kinetochore, in esophageal carcinoma and its correlation with clinicopathological features. In cancer cells multipolar mitotic spindles and various centrosomal anomalies, such as supernumerary centrosomes, centrosomes of abnormal size and shape, and prematurely split centrosomes are frequently observed [1,2,3] It is conceivable that such abnormalities disrupt normal chromosomal segregation, producing aneuploid cells and causing chromosomal instability (CIN). Human CENPH protein was recently isolated and shown to localize in the inner plate together with CENP-A and CENP-C and is a fundamental component of the active centromere complex [12,13]. Studies using budding yeast have shown that a molecular core consisting of CENP-A, CENP-C, CENPH, and Ndc80/HEC plays a central role in linking centromeres to the spindle microtubule [14]
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