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Objective To investigate the expressions of HOXA11 and β-catenin proteins in colorectal serrated lesions and their roles in carcinogenesis. Methods A total of 252 cases of colorectal biopsy specimens in Shanxi Dayi Hospital from January 2012 to December 2016 were analyzed retrospectively, including 97 serrated lesions, 46 common adenomas, 109 adenocarcinomas, and 24 normal colorectal mucosa tissues were selected as controls. The expressions of HOXA11 and β-catenin proteins were detected by immunohistochemical EnVision method. Methylation of HOXA11 gene was detected by specific methylation polymerase chain reaction (MSP) in 25 paraffin-embedded adenocarcinoma tissues. Results In 97 serrated lesions, 29 (29.9％) occurred in the left colon;in 46 common adenomas, 27 (58.7％) occurred in the left colon;in 109 adenocarcinomas, 76 (69.7％) occured in the left colon. The difference of the occurrence location among three groups was statistically significant (χ2 = 34.75, P< 0.01). The heterotopic expression rate ofβ-catenin protein in serrated lesions, common adenomas and adenocarcinomas was significantly higher than that in normal mucosae [96.9％ (94/97), 82.6％ (38/46), 86.2％ (94/109) vs. 0 (0/24), P < 0.01]. The heterotopic expression of β-catenin protein was found in serrated lesions and the co-expression of cytoplasm and nucleus was found in common adenomas and adenocarcinomas. The normal expression rate of HOXA11 protein in serrated lesions, common adenomas and adenocarcinomas was lower than that in normal mucosae [33.0％ (32/97), 67.4％ (31/46), 48.6％ (53/109) vs. 100.0％ (24/24), all P< 0.05]. The methylation rate of HOXA11 gene was 84.0％ (21/25). Conclusion The ectopic expression of β-catenin in colorectal serrated lesions suggests that it is associated with serrated lesions, and the low expression of HOXA11 may be an early event in the carcinogenesis of serrated lesions.
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Objective@#To explore the expression of long noncoding RNA (lncRNA) HOXA11-AS in esophageal squamous cell carcinoma tissues and the relationship of HOXA11-AS level with clinical outcomes.@*Methods@#Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression level of HOXA11-AS in cell lines HET-1A, EC9706, EC109, and in tumor tissue and paired adjacent tissue samples from 73 ESCC patients who received surgical resection.The correlations of the expression level of HOXA11-AS with clinicopathological features and prognosis were also analyzed.@*Results@#The relative expression levels of HOXA11-AS in tumor tissue and paired adjacent tissue were 0.832±0.387 and 2.486±1.087, respectively, with significant difference (P<0.001). The expression of HOXA11-AS was upregulated in 63.0%(46/73)ESCC tissues. The relative expression levels of HOXA11-AS in HET-1A, EC-9706 and EC-109 cells were 1.000, 23.553±3.221 and 17.217±1.968, respectively. The expression level of HOXA11-AS was upregulated in ESCC cell lines (P<0.001). High expression level of HOXA11-AS was correlated with histological grade and lymph node metastasis of ESCC patients (P<0.05). However, it was not associated with the age, gender, depth of infiltration and TNM staging (P>0.05). The median overall survival (OS) and median disease-free survival (DFS) of patients with low HOXA11-AS expression were 43 months and 42 months, respectively, significantly longer than 37 months and 28 months of patients with HOXA11-AS high expression (P<0.05). Cox model multivariate analysis showed that the expression of HOXA11-AS and lymph node metastasis were independent factors of poor prognosis of ESCC patients.@*Conclusions@#The expression of HOXA11-AS is upregulated in esophageal cancer cell lines and tissues. High expression of HOXA11-AS is associated with poor prognosis of ESCC patients.Therefore, LncRNA HOXA11-AS may serve as a predictive marker of postoperative ESCC patients.
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PURPOSE: Homeobox (HOX) genes are essential developmental regulators that should normally be in the silenced state in an adult brain. The aberrant expression of HOX genes has been associated with the prognosis of many cancer types, including glioblastoma (GBM). This study examined the identity and role of HOX genes affecting GBM prognosis and treatment resistance. MATERIALS AND METHODS: The full series of HOX genes of five pairs of initial and recurrent human GBM samples were screened by microarray analysis to determine the most plausible candidate responsible for GBM prognosis. Another 20 newly diagnosed GBM samples were used for prognostic validation. In vitro experiments were performed to confirm the role of HOX in treatment resistance. Mediators involved in HOX gene regulation were searched using differentially expressed gene analysis, gene set enrichment tests, and network analysis. RESULTS: The underexpression of HOXA11 was identified as a consistent signature for a poor prognosis among the HOX genes. The overall survival of the GBM patients indicated a significantly favorable prognosis in patients with high HOXA11 expression (31±15.3 months) compared to the prognoses in thosewith low HOXA11 expression (18±7.3 months, p=0.03). When HOXA11 was suppressed in the GBM cell lines, the anticancer effect of radiotherapy and/or temozolomide declined. In addition, five candidate mediators (TGFBR2, CRIM1, TXNIP, DPYSL2, and CRMP1) that may confer an oncologic effect after HOXA11 suppression were identified. CONCLUSION: The treatment resistance induced by the underexpression of HOXA11 can contribute to a poor prognosis in GBM. Further investigation will be needed to confirm the value of HOXA11 as a potential target for overcoming the treatment resistance by developing chemo- or radiosensitizers.
Subject(s)
Adult , Humans , Brain , Cell Line , Genes, Homeobox , Glioblastoma , In Vitro Techniques , Microarray Analysis , Prognosis , RadiotherapyABSTRACT
Objective To examine HOXA11,ER and PR expression in human endometrial hyperplasia and adenocarcinoma.Methods The immunohistochemistry was applied to analyze the level of HOXA11、ER and PR expression in the proliferative endometria,simple hyperplasia and endometrial adenocarcinoma.Results The expression level of HOXA11 in the endometrial hyperplasia and adenocarcinoma was significantly higher than that of proliferative endometrium(P