Prognostic value of humbug gene overexpression in stage II colon cancer

Wang, JiYi; Sabo, Edmond; Kethu, Sripathi R.; Tavares, Rosemarie; Branda, Mark; Simao, Lelia; Wands, Jack R.; Resnick, Murray B.

doi:10.1016/j.humpath.2006.07.009

Cited by 27 publications

(34 citation statements)

References 29 publications

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“…In contrast, the expression level and role of the humbug gene in human cancer has not been clarified. A recent report revealed that humbug is overexpressed and may be a useful prognostic marker for colon cancer (27). This report showed that expression levels of humbug correlate with histological grade and tumor behavior.…”

Section: Discussionmentioning

confidence: 85%

Overexpression of humbug promotes malignant progression in human gastric cancer cells

Lee

2008

Oncol Rep

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Abstract. Two human gastric cancer cell lines of differing invasive potential, SNU-484 and SNU-638 cells, were examined using subtractive suppression hybridization in a search for any genes associated with metastasis. Of the eight cDNAs identified as being differentially expressed genes, it was determined that humbug, which encodes a truncated isoform of aspartyl (asparaginyl) ß-hydroxylase (AAH) missing catalytic domain, was overexpressed in highly invasive SNU-638 cells. Expression analysis showed that the mRNA expression level of humbug was correlated with invasive potential in various human gastric cancer cell lines. The forced expression of humbug to the human gastric cancer cell line AGS increased its anchorage-independent growth in 0.3% agar without affecting cell proliferation. Furthermore, humbug-transfected cells migrated more actively and showed an increased invasion rate relative to vector-transfectants or parental AGS in vitro. This is the first demonstration that humbug, a truncated form of AAH, can be overexpressed during the malignant progression of human gastric cancer cells and that it can function as a metastasis-inducing gene.

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Section: Discussionmentioning

confidence: 85%

Overexpression of humbug promotes malignant progression in human gastric cancer cells

Lee

2008

Oncol Rep

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“…The aspartyl-(asparaginyl)- β -hydroxylase (ABH) and/or humbug genes have been documented to be overexpressed in a variety of malignant neoplasms, including those of colonic, pancreatic, biliary, or hepatic origin [18–23]. The present study demonstrates that in non–small cell lung carcinomas, ABH/humbug immunoreactivity is strikingly increased relative to normal lung parenchyma, and high levels of ABH/humbug immunoreactivity are negatively correlated with survival, particularly in squamous cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…Normal and mature tissues generally express low levels of ABH, with the notable exception of placental trophoblasts [19], which are naturally highly motile and invasive. In addition, previous studies demonstrated that up-regulation of ABH and/or humbug correlates with poor cancer prognosis [21,23]. Because the monoclonal antibody FB50 binds to the N-terminus of ABH, which is virtually identical to humbug, both ABH and humbug are equally detected by immunohistochemical staining.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic value of aspartyl (asparaginyl)-β-hydroxylase/humbug expression in non–small cell lung carcinoma

et al. 2009

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SummaryDespite improvements in the detection and use of biomarkers, including epidermal growth factor receptor, ERCC1, and p16, the 5-year survival rate with non-small cell lung cancer remains at 15%. This suggests that additional biomarkers are needed to better prognosticate clinical course and guide therapeutic approaches. Previous studies showed that increased levels of aspartyl (asparaginyl)-β-hydroxylase and a highly related molecule, humbug, correlate with clinical course and survival with hepatic, biliary, pancreatic, and colon carcinomas. We now characterize the prognostic use of aspartyl (asparaginyl)-β-hydroxylase/humbug immunoreactivity in different subtypes of non-small cell lung cancer. Tissue microarrays including 375 paraffin-embedded non-small cell lung cancers (195 adenocarcinomas; 18 bronchioloalveolar carcinomas; 113 squamous cell carcinomas; and 49 large cell carcinomas) were immunostained with FB50 monoclonal antibody, which recognizes human aspartyl (asparaginyl)-β-hydroxylase/humbug. Immunoreactivity (intensity and distribution) in neoplastic cells were scored under code, and data were subjected to univariate and Cox multivariate analyses, adjusting for age, stage, and treatment. High levels of FB50 immunoreactivity were more often detected in adenocarcinomas (28% for adenocarcinoma, 17% for bronchioloalveolar carcinoma), compared with squamous cell carcinomas (10%) and large cell carcinomas (10%). Univariate analysis demonstrated inverse relationships between intensity of FB50 immunoreactivity and survival with squamous cell carcinoma (P = .004), and a strong trend with respect to large cell carcinoma (P = .057). Cox multivariate test showed that FB50 immunoreactivity (P = .025), clinical stage (P = .029), and tumor size (P = .0001) were all independent predictors of survival with squamous cell carcinoma. High levels of FB50 immunohistochemical staining correlate with poor prognosis in non-small cell lung cancer, particularly squamous cell carcinoma subtype. Therefore, FB50 immunoreactivity may be useful in defining patient subsets that are likely to benefit from adjuvant therapy.

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“…Whole sections of five cases of PDC which had focal well differentiated areas were also assessed. In addition a tissue microarray (TMA) constructed previously containing 111 cases of primarily moderately to well differentiated CRC was assessed [22]. …”

Section: Methodsmentioning

confidence: 99%

Expression of the intestinal biomarkers Guanylyl cyclase C and CDX2 in poorly differentiated colorectal carcinomas

et al. 2010

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Guanylyl cyclase C a receptor for bacterial diarrheagenic enterotoxins is expressed selectively by intestinal epithelium and is an endogenous downstream target of CDX2. The expression of Guanylyl cyclase C is preserved throughout the adenoma/carcinoma sequence in the colorectum. Detection of Guanylyl cyclase C expression by RT-PCR is currently being validated as a technique to identify occult lymph node metastases in patients with colorectal cancer and for circulating cells in the blood for postoperative surveillance. Although Guanylyl cyclase C is widely expressed by well differentiated colorectal cancer, its expression in poorly differentiated colorectal cancer has not been evaluated. A tissue microarray was created from 69 archival specimens including 44 poorly differentiated, 15 undifferentiated or medullary and 10 signet ring cell colorectal carcinomas. Matched normal colonic mucosa was used as a positive control. Immunohistochemical staining for Guanylyl cyclase C and CDX2 was evaluated as positive or negative based on at least a 10% extent of staining. Out of the 69 tumor samples 75%, 47%, and 90% of the poorly differentiated, medullary and signet ring cell tumors were positive for Guanylyl cyclase C and 75%, 40% and 90% of these subsets were positive for CDX2 respectively. There was excellent correlation between Guanylyl cyclase C and CDX2 expression on a case per case basis (p<0.0001). There was also a statistically significant difference in the GCC staining pattern between MC and PDC (p=0.05). Immunopositivity for Guanylyl cyclase C was greater than 95% in a separately stained microarray series of well/ moderately differentiated colorectal carcinomas. In conclusion, Guanylyl cyclase C expression is lost in a quarter of poorly differentiated and half of undifferentiated colorectal carcinomas. Therefore the utility of Guanylyl cyclase C expression as a diagnostic marker for colorectal carcinoma may be questionable in poorly differentiated colorectal neoplasms.

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Prognostic value of humbug gene overexpression in stage II colon cancer

Cited by 27 publications

References 29 publications

Overexpression of humbug promotes malignant progression in human gastric cancer cells

Overexpression of humbug promotes malignant progression in human gastric cancer cells

Prognostic value of aspartyl (asparaginyl)-β-hydroxylase/humbug expression in non–small cell lung carcinoma

Expression of the intestinal biomarkers Guanylyl cyclase C and CDX2 in poorly differentiated colorectal carcinomas

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