Underexpression of HOXA11 Is Associated with Treatment Resistance and Poor Prognosis in Glioblastoma / Journal of the Korean Cancer Association, 대한암학회지

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.

Research progress and prospect of the relationship between homeodox genes' family and development of digestive system tumors / 国际外科学杂志

Homeobox gene is an important gene family of developmental regulatory in the body.It is highly conserved in the evolutionary process.It is widely found in nervous,digestive,respiratory,circulatory,blood and genitourinary system,involved in rcgulating the growth and development of individuals,cells' proliferation,differentiation,apoptosis and other processes.The present studies show that the abnormal expressions of homeobox genes are closely related to the occurrence,development and prognosis of human multiple malignancies.In this paper,the research progress and prospect of the relationship between homeobox genes' family and development of digestive system tumors are reviewed.

Research progress and prospect of the relationship between homeodox genes' family and development of digestive system tumors / 国际外科学杂志

Homeobox gene is an important gene family of developmental regulatory in the body.It is highly conserved in the evolutionary process.It is widely found in nervous,digestive,respiratory,circulatory,blood and genitourinary system,involved in rcgulating the growth and development of individuals,cells' proliferation,differentiation,apoptosis and other processes.The present studies show that the abnormal expressions of homeobox genes are closely related to the occurrence,development and prognosis of human multiple malignancies.In this paper,the research progress and prospect of the relationship between homeobox genes' family and development of digestive system tumors are reviewed.

Immunohistochemical expression of NANOG in urothelial carcinoma of the bladder

Urothelial carcinoma is a common malignant neoplasm that has a poor prognosis and a high frequencyof recurrence and metastasis. Constant disease surveillance with periodic and long term cystoscopyexamination is necessary for management of the disease. However, the monitoring and therapyregimen is expensive, incurring a massive burden to patients and the government. Therefore, thedevelopment of specific biomarkers for urothelial carcinoma at an early stage and recurrence detectionbecomes a priority. Homeobox genes are a family of genes that are involved in tumourigenesis.They might be potential prognostic markers for urothelial carcinoma. The study investigated theexpression pattern of NANOG which is one of a homeobox gene in different stages and grades ofurothelial carcinoma. NANOG expressions were also correlated with patient demographic factors andclinicopathological parameters. The expression of NANOG in 100 formalin-fixed paraffin-embeddedurothelial carcinoma tissues was determined by immunohistochemistry. Immunohistochemistryshowed positive expression of NANOG in all specimens with detection in the cytoplasm, nucleiand the nuclear membrane of the cancer cells. The immunohistochemical expression of NANOGincreased across stages and grades of the tumour. The expression of NANOG was not significantlyassociated with demographic factors; gender (p = 0.376), race (p = 0.718) and age (p = 0.058) aswell as with most of the clinicopathological parameters; pathological stage (p = 0.144), grade (p =0.625), lymph node involvement (p = 0.174) and distant metastasis (p = 0.228). However, NANOGexpression showed significant correlation with tumour invasion (p = 0.019). We concluded thatNANOG might be a potential biomarker for early diagnosis of urothelial carcinoma of the bladder.

The relationship between the expressions of caudal type homeobox genes 2,tumor necrosis factor-α protein expression,Helicobacter pylori infection and chronic gastropathy with intestinal metaplasia / 中国医师进修杂志

Objective To investigate the relationship between chronic gastropathy with intestinal metaplasia (IM) and caudal type homeobox genes 2 (Cdx2),tumor necrosis factor-α (TNF-α),Helicobacter pylori (Hp) infection.Methods Onehundred and thirty patients underwent gastroscopy were divided into 2 groups by typical pathological type:gastritis group (30 cases) and IM group [100 cases,including mild IM group (30 cases),moderate IM group (35 cases),severe IM group (35 cases)].Hp infection was confirmed.The expressions of Cdx2 and TNF-α protein was evaluated by immunohistochemistry.Results The positive expression rates of Cdx2 and TNF-α protein in IM group were significantly higher than those in gastritis group [78.0％(78/100) vs.6.7％(2/30),60.0％(60/100) vs.16.7％(5/30)],and there were statistical differences (P ＜ 0.01).The positive expression rates of Cdx2 and TNF-α protein in positive and negative Hp infection in IM group were significantly higher than those in gastritis group [Cdx2 protein:79.4％(50/63) vs.1/10,75.7％(28/37) vs.5.0％(1/20);TNF-α:74.6％(47/63) vs.4/10,35.1％(13/37)vs.5.0％ (1/20)],and there were statistical differences (P ＜ 0.01).The positive expression rate of Cdx2 protein in moderate IM group and severe IM group were significantly higher than those in mild IM group [80.0％ (28/35) and 97.1％ (34/35) vs.53.3％ (16/30)],in severe IM group were significantly higher th.an those in moderate IM group,and there were statistical differences (P ＜0.05).There were no statistical differences in the positive expression rate of Cdx2 protein of difference Hp infection among the 4 groups (P＞0.05).There were no statistical differences in the positive expression rate of TNF-α protein between mile IM group and moderate IM group (P ＞ 0.05).The positive expression rate of TNF-α protein in severe IM group was significantly higher than that in mild IM group and moderate IM group [80.0％(28/35) vs.40.0％(12/30) and 57.1％(20/35)],and there were statistical differences (P ＜ 0.05).The positive expression rate of TNF-α protein of positive Hp infection patients in gastritis group,mild IM group,moderate IM group and severe IM group were significantly higher than those of negative Hp infection patients (4/10 vs.1/20,47/63vs.13/37,10/18 vs.2/12,15/21 vs.5/14,22/24 vs.6/11),and there were statistical differences (P ＜ 0.05).Conclusions The expressions of Cdx2 and TNF-α protein and Hp infection are closely related with IM.Therefore,testing the level of Cdx2 and TNF-α protein expressions can help to judge the degree of IM,which provides a basis for reversing IM.

Effect of homeobox A2 gene RNA interference on HCC cell behavior / 安徽医科大学学报

Objective To study the role of homeobox A2(HOXA2) gene in cell growth,cellcycle and apoptosis of hepatoma cells, and discuss the feasibility that HOXA2 gene would be a potential therapy target of hepatoma. Methods Real-time quantitative polymerase chain reaction and revers transcriptional polymerase chain reaction were performed to examine HOXA2 expression in tumorous and non-tumorous tissue of patients was matched with liver cancer. siRNAs were chemically synthesized to interference HOXA2 in PLC/PRF/5 and MHCC-97L cells. Growth curve and soft-agar colony formation assay were performed to evaluate cell growth, and cell cycle and apop-tosis were analyzed by flow cytometry. Results HOXA2 was upregulated in HCC samples compared with matched non-tumor tissues(P<0.05). Two siRNAs against HOXA2 gene were designed and synthesized to specially knock-down HOXA2 in PLC/PRF/5 and MHCC-97L cells. HOXA2 knockdown inhibited cellular growth and soft-agar colony formation in PLC/PRF/5 and MHCC-97L cells. And Fowcytometry analysis revealed that HOXA2 knock-down by RNA interference could result in G1 arrest and S decrease and promoted cellular apoptosis. ConclusionHOXA2 gene has an important role in cell growth of hepatoma cells.

Relationships Between the Expressions of CDX1 and CDX2 mRNA and Clinicopathologic Features in Colorectal Cancers

BACKGROUND: CDX1 and CDX2 are members of the caudal-type homeobox gene family and control the proliferation and differentiation of intestinal mucosal cells. Their expressions are commonly reduced in colorectal cancer, but reports about the relationships between their expressions and clinicopathologic features are rare. The aim of this study was to examine the expressions of CDX1 and CDX2 mRNAs in colorectal cancers and to assess the relationships between their expressions and clinicopathologic features. METHODS: CDX1 and CDX2 mRNA expressions were analyzed by real-time polymerase chain reaction in 48 colorectal cancers and in adjacent non-tumorous normal mucosal tissue. RESULTS: CDX1 and CDX2 mRNA expressions were significantly reduced in colorectal cancer tissues versus normal mucosal tissues (p=0.001, p=0.042, respectively). As compared with paired normal mucosal tissues, colorectal tissues showed reduced CDX1 mRNA expression in 64.6% (31/48) and reduced CDX2 mRNA expression in 66.7% (32/48) of cases. A statistically significant positive correlation was found between the expressions of CDX1 mRNA and CDX2 mRNA in colorectal cancer (r=0.543, p< 0.001). However, the expressions of CDX1 and CDX2 mRNAs were not related to age, sex, cancer location, differentiation, lymphatic or vascular invasion, lymph node metastasis, stage or serum carcinoembryonic antigen level. CONCLUSIONS: CDX1 and CDX2 mRNA expressions were found to be significantly reduced in colorectal cancers, but these expressional changes were not found to be related to clinicopathologic features.

Relationship of CDX1 mRNA and CDX2 mRNA expression and clinicopathologic features in colorectal cancers / 대한내과학회지

BACKGROUND: CDX1 and CDX2, members of the caudal-type homeobox gene family, control proliferation and differentiation of intestinal mucosal cells. Their expression is reduced commonly in colorectal cancers, but reports about the relationship between their expression and the clinicopathologic features are rare. The aim of this study was to examine CDX1 mRNA and CDX2 mRNA expression in colorectal cancers and to assess the relationship between their expression and the clinicopathologic features. METHODS: CDX1 mRNA and CDX2 mRNA expression were analyzed by real-time polymerase chain reaction in 48 colorectal cancers and their adjacent non-tumorous normal mucosas. RESULTS: CDX1 mRNA and CDX2 mRNA expression were decreased significantly in colorectal cancers than in normal mucosas (p=0.001, p=0.042, respectively). In comparison with paired normal mucosas, colorectal cancers showed decreased CDX1 mRNA expression in 64.6% (31/48) and decreased CDX2 mRNA expression in 66.7% (32/48). There was a statistically significant correlation between CDX1 mRNA and CDX2 mRNA expression in colorectal cancers (r=0.543, p<0.001). CDX1 mRNA and CDX2 mRNA expression were not related to age, sex, location of cancer, differentiation, lymphatic or vascular invasion, lymph node metastasis, stage and serum carcinoembryonic antigen level in colorectal cancers. CONCLUSION: CDX1 mRNA and CDX2 mRNA expression were decreased significantly in colorectal cancers, but were not related to the clininopathologic features.