Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1326912 (tumorigenesis)
 57,481 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prognosis of patients with esophageal cancer remains poor. TNM classification is not sufficient to predict their prognosis, and novel predictive markers of the prognosis of esophageal cancer patients are therefore needed. Poly A binding protein, cytoplasmic 1 (PABPC1) plays a role in post-transcriptional control of mRNA and may be involved in tumorigenesis. PABPC1 expression has not been studied in esophageal cancer. Expression of PABPC1 was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR) using LightCycler in 41 primary esophageal squamous cell carcinomas (ESCCs) and their paired normal esophageal mucosa. We examined the correlation between PABPC1 expression and the clinicopathological factors and prognosis of ESCC patients. Reduced expression of PABPC1 was accompanied by locally invasive tumors (t-factor, p=0.0145) and more advanced tumors (pathologic stage, p=0.0264). Moreover, ESCC patients with low PABPC1 mRNA expression had a significantly shorter postoperative survival time than those with high expression (median survival, 3.1 vs. 6.5 months, p=0.002). In esophageal cancer, reduced expression of PABPC1 was correlated with local tumor progression and poor prognosis after surgery.
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PMID:Expression and prognostic roles of PABPC1 in esophageal cancer: correlation with tumor progression and postoperative survival. 1646 28

Epigenetic mechanisms involving DNA methylation and chromatin remodeling are important in silencing tumor suppressor genes (TSG) in various malignancies, including renal cell carcinoma (RCC). DLC1 (deleted in liver cancer 1)/ARHGAP7 is a recently identified 8p22 candidate TSG. Frequent methylation of the DLC1 promoter with resultant gene silencing has been reported in several tumors, but not in RCC yet. We examined DLC1 promoter methylation in 34 primary RCCs and the corresponding non-malignant tissues, and the correlation of DLC1 methylation with the clinicopathological characteristics of RCC patients. Although DLC1 methylation and downregulation were only detected in one of seven RCC cell lines using methylation-specific PCR (MSP) and semi-quantitative reverse-transcription PCR, we found that the DLC1 promoter was methylated in 35% (12/34) of primary RCC tumors, which was further confirmed by direct sequencing of MSP products and high-resolution bisulfite genomic sequencing. In contrast, only one of the 34 (3%) non-malignant renal tissues had weak methylation. Aberrant DLC1 methylation appeared to be a relatively early event during renal tumorigenesis since 33% of the RCC tumors with pT1 (TNM staging) showed methylation, which is similar to other late stage tumors. Thus, our results demonstrated that DLC1 methylation occurs in a subset of RCC tumors and may play a role in renal carcinogenesis.
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PMID:Aberrant methylation of the 8p22 tumor suppressor gene DLC1 in renal cell carcinoma. 1702 74

CHFR was recently identified as an early mitotic checkpoint that delays transition to metaphase in response to mitotic stress. Although studies have shown that CHFR is relevant to tumorigenesis, no previous report has investigated whether polymorphisms in the CHFR gene are associated with the risk of cancer development. Here, we genotyped polymorphisms in the CHFR gene and analyzed the possible associations of single polymorphisms and haplotypes with the risk and clinicopathological characteristics of colorectal cancer. Six coding SNPs in the CHFR gene were genotyped in 462 colorectal cancer patients and 245 healthy normal controls, using either the TaqMan assay or direct sequencing. Our results revealed that the V539M polymorphism was significantly associated with a lower risk of colorectal cancer (P=0.03; OR, 0.533; 95% CI, 0.302-0.94), and significantly correlated with no distant metastasis (M0 stage), different TNM stage, and microsatellite instability (MSI) among the colorectal cancer patients. Among the five tested haplotypes, hap 10 (TGACTA) was significantly associated with a lower risk of colorectal cancer (P=0.017; OR, 0.496; 95% CI, 0.279-0.883), and colorectal cancer patients carrying this haplotype showed no distant metastasis, different TNM stage, and microsatellite instability at a significantly higher frequency. These results reveal for the first time that polymorphisms in the CHFR gene are associated with colorectal cancer susceptibility.
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PMID:Coding region polymorphisms in the CHFR mitotic stress checkpoint gene are associated with colorectal cancer risk. 1807 53

The novel tumor suppressor RASSF1A is frequently inactivated during human tumorigenesis by promoter methylation. In this study, we detected the RASSF1A promoter methylation by methylated-specific PCR and investigated RASSF1A gene expression by semi-quantitative RT-PCR and immunohistochemical staining in 36 cases of breast cancer and their adjacent normal tissues in Chinese women. The promoter methylation of the RASSF1A gene was found to be a frequent event in the breast cancers (61.1%). RASSF1A methylation was not found in the matched adjacent normal tissues. The loss frequency of RASSF1A mRNA was 33.3% and that of the RASSF1A protein was 44.4% in breast cancers. RASSF1A mRNA and protein were all expressed in adjacent normal tissues. The mRNA and protein expression level of RASSF1A was significantly lower in breast cancer than in adjacent normal tissue. However, the promoter methylation of the RASSF1A gene in breast cancers were not correlated with clinical parameters, such as ages, histological types, TNM stages and lymph node metastases. Thus, the promoter methylation of RASSF1A was one reason for the low level of RASSF1A mRNA and protein expression and was a frequent event in primary sporadic breast tumorigenesis in Chinese women.
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PMID:Expression and promoter methylation of the RASSF1A gene in sporadic breast cancers in Chinese women. 1842 70

In order to define more effective predictive markers for clinical management and prognosis, we evaluated the expression of cyclin D1 and survivin in large papillary thyroid carcinoma (LPTC) and microcarcinoma (PTM). Sixty-seven patients operated for papillary carcinoma (36 of which with PTM) were considered. Immunochemistry for cyclin D1 and survivin was performed in samples from tumor mass and nodal metastases. There were not significant differences between LPTC and PTM as to patients personal data, TNM or MACIS staging, nodal invasion and multifocality, while capsular invasion was significantly more frequent in LPTC. Cyclin D1 and survivin were expressed at a very high rate and almost to the same extent in LPTC and PTM, both in tumoral mass and in nodal metastases. Survivin showed only cytoplasmic expression. Cyclin D1 and survivin over-expression are probably early events in tumorigenesis of thyroid papillary carcinoma but their full role in the process of tumor progression and their clinical value are still to be investigated.
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PMID:Survivin and cyclin D1 are jointly expressed in thyroid papillary carcinoma and microcarcinoma. 1857 19

The prognosis of the hepatocellular carcinoma is influenced by its invasion and metastasis. Interacting with a number of oncogenes, HBV infection is a high risk factor for HCC. Overexpression of Focal adhesion kinase (FAK), a novel oncogene, has been suggested to play an important role in tumorigenesis and progression of many cancers, including HCC. However, the relationship between HBV infection and FAK for HCC prognosis is still unclear. A retrospective study of 89 archival specimens of subjects with histologically confirmed HCC was carried out. Immunohistochemistry was utilized to examine the expression of FAK. Then the FAK expression was analyzed with index of HCC, especially with HBsAg and HBV DNA. FAK overexpression was detected in 38/89 of the tumors. FAK overexpression in HCC significantly correlated with HBsAg (P = 0.033), HBV DNA level (P = 0.005), vascular invasion of HCC (P = 0.000*), and TNM stage (P = 0.003). FAK-positive patients exhibited a lower survival rate compared with those with negative FAK expression. Overexpression of FAK might have a correlation with HBV infection and contribute to HCC progression, raising the possibility of FAK overexpression as a potential marker for a poor prognosis in HCC.
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PMID:Overexpression and significance of focal adhesion kinase in hepatocellular carcinoma and its relationship with HBV infection. 1902 Oct 2

Growing evidence suggests microRNAs (miRNAs) have an important role in tumorigenesis. MicroRNA-21 (miR-21) is up-regulated in many malignant tumors, including breast cancer. Its association with clinicopathologic features and expression of PTEN (phosphatase and tensin homolog deleted on chromosome 10), one of its target genes, in breast cancer has not been reported systematically. To further determine the potential involvement of miR-21 in breast cancer, we have evaluated the expression level of miR-21 by stem-loop real-time RT-PCR based on SYBR-Green I in human invasive ductal carcinoma of the breast, and we have correlated the results with clinicopathologic features and PTEN protein expression. Matched non-tumor and tumor tissues of 40 human invasive ductal carcinoma of the breast were analyzed for miR-21 expression by stem-loop real-time RT-PCR based on SYBR-Green I. Immunohistochemistry (IHC) was used to estimate PTEN expression in tumor tissue. The expression levels of miR-21 were correlated with PTEN and commonly used clinicopathologic features of breast cancer. The stem-loop real-time RT-PCR based on SYBR-Green I was sensitive and specific enough to detect miR-21. Expression levels of miR-21 were significantly higher in tumor tissues than the levels in matched non-tumor tissues (P=0.000). Expression of miR-21 was negatively correlated with expression of PTEN (P=0.013). Up-regulated miR-21 expression was associated with lymph node positivity (P=0.01), higher proliferation index (ki67>10%) (P=0.03) and advanced breast cancer TNM clinical stage (P=0.021). These findings suggest that PTEN is possibly one of the targets of miR-21 in breast cancer and high expression of mir-21 indicates a more aggressive phenotype.
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PMID:Clinical significance of miR-21 expression in breast cancer: SYBR-Green I-based real-time RT-PCR study of invasive ductal carcinoma. 1921 25

Mounting evidence suggests that neuronal PAS domain protein 2 (NPAS2) and other circadian genes are involved in tumorigenesis and tumor growth, possibly through their control of cancer-related biologic pathways. A missense polymorphism in NPAS2 (Ala394Thr) has been shown to be associated with risk of human tumors including breast cancer. The current study further examined the prognostic significance of NPAS2 in breast cancer by genotyping the Ala394Thr polymorphism and measuring NPAS2 expression. DNA extracted from 348 breast cancer tissue samples was analyzed for NPAS2 genotype using the TaqMan allelic discrimination assay. Of these, 287 also had total RNA available for use in real-time PCR assays to determine NPAS2 expression. NPAS2 genotypes and expression levels were analyzed for associations with prognostic outcomes, as well as correlations with clinical characteristics. A high level of NPAS2 expression was strongly associated with improved disease free survival (AHR = 0.43, 95% CI: 0.21-0.86, P trend = 0.022) and overall survival (AHR = 0.42, 95% CI: 0.19-0.96, P trend = 0.036). In addition, there was a borderline, but nonsignificant association between the NPAS2 genotype corresponding to Thr394Thr and disease free survival (AHR = 1.82, 95% CI: 0.96-3.46). The Ala/Ala, Ala/Thr, and Thr/Thr genotypes were also differentially distributed by tumor severity, as measured by TNM classification (chi (2) (6df, N = 344) = 14.96, P = 0.020). These findings provide the first evidence suggesting prognostic significance of the circadian gene NPAS2 in breast cancer.
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PMID:The circadian gene NPAS2 is a novel prognostic biomarker for breast cancer. 1964 6

NAD(P)H: quinone oxidoreductase 1 (NQO1), a cytosolic enzyme which catalyzes the two-electron reduction of quinone compounds, has been suggested to prevent the generation of semiquinone free radicals and reactive oxygen species, thus protecting cells from oxidative damage. However, the enzymatic activity of NQO1 strongly depends on the individual genetic polymorphism of the NQO1 gene. A common NQO1 polymorphism is a C to T transition at position 609, which results in an inactive enzyme. Recent studies showed that NQO1 is an important enzyme for stabilizing p53 protein, which is involved in anti-tumorigenesis. Thus, the lack of enzymatic activity in the homozygous C609T NQO1 polymorphism may play a pivotal role in tumor development. This study aimed to investigate the relationship between C609T NQO1 polymorphism and p53 expression in human hepatocellular carcinoma (HCC). Genotyping of NQO1 was performed on 100 HCC specimens by PCR-RFLP analysis. In addition, NQO1 and p53 protein expression in HCC samples at different TNM stages was determined by immunohistochemistry. Our data showed that (1) the frequency of C609T NQO1 was significantly increased in TNM stage III HCC patients; (2) no significant association was found between p53 expression and C609T polymorphism of NQO1 gene; and (3) a tumor/non-tumor (T/N) ratio > 1.27 of NQO1 expression revealed by real-time qPCR analyses was positively correlated with poorer survival in patients with tumors >5 cm, suggesting that an increase of NQO1 expression may be an indicator of advanced tumor progression. This study provides important information about NQO1 genotypes and its expression to HCC tumor development and progression.
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PMID:Analysis of NQO1 polymorphisms and p53 protein expression in patients with hepatocellular carcinoma. 1968 91

Metastatic renal cell carcinoma (RCC) is highly resistant to conventional systemic treatments, including chemotherapy, radiotherapy and hormonal therapies. Previous studies have shown over-expression of EGFR is associated with high grade tumors and a worse prognosis. Recent studies suggest anticancer therapies targeting the EGFR pathway have shown promising results in clinical trials of RCC patients. Therefore, characterization of the level and localization of EGFR expression in RCC is important for target-dependent therapy. In this study, we investigated the clinical significance of cellular localization of EGFR in human normal renal cortex and RCC. RCC and adjacent normal kidney tissues of 63 patients were obtained for characterization of EGFR expression. EGFR protein expression was assessed by immunohistochemistry on a scale from 0 to 300 (percentage of positive cells x staining intensity) and Western blotting. EGFR membranous staining was significantly stronger in RCC tumors than in normal tissues (P < 0.001). In contrast, EGFR cytoplasmic staining was significantly higher in normal than in tumor tissues (P < 0.001). The levels of membranous or cytoplasmic EGFR expression in RCC tissues were not correlated with sex, tumor grade, TNM stage or overall survival (P > 0.05). These results showed abundant expression of membranous EGFR in RCC, and abundant expression of cytoplasmic EGFR in normal tissues. EGFR expression in RCC was mostly located in the cell membrane, whereas the EGFR expression in normal renal tissues was chiefly seen in cytoplasm. Our results suggest different locations of EGFR expression may be associated with human renal tumorigenesis.
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PMID:Characterization of membranous and cytoplasmic EGFR expression in human normal renal cortex and renal cell carcinoma. 1974 98


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