Identification of gene signatures for invasive colorectal tumor cells

Wiese, Anja; Auer, Johannes; Laßmann, Silke; Nährig, Jörg; Rosenberg, Robert D.; Höfler, Heinz; Rüger, Rüdiger; Werner, Martin

doi:10.1016/j.cdp.2007.07.003

Cited by 55 publications

(42 citation statements)

References 49 publications

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“…3E). These results are consistent with ones from other studies on bladder (27) and colon cancer (31). It is important to know the extent of invasion at the time of treatment of gastric cancer.…”

Section: Discussionsupporting

confidence: 82%

Clinicopathological and biological significance of CDC28 protein kinase regulatory subunit 2 overexpression in human gastric cancer

Tanaka

Matsuzaki

Mimori³

et al. 2011

Int J Oncol

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Abstract. CDC28 protein kinase regulatory subunit 2 (CKS2)is a cyclin-dependent kinase subunit (cKS) family member that participates in cell cycle regulation. Few studies have investigated its involvement in gastric cancer. In this study, we focused on the clinical and biological significance of CKS2 overexpression in gastric cancer. The expression of CKS2 mRNA was studied by real-time quantitative reverse transcription polymerase chain reaction, and the expression status in each tumor was examined to varify whether any correlation existed with clinical and pathological factors. In addition, an immunohistochemical study was performed in selected samples. Moreover, we examined the impact of CKS2-siRNA in a gastric cancer cell line. A significantly higher expression of CKS2 mRNA was found in tumor tissues compared to paired normal tissues (p<0.01). Immunohistochemical analyses led to similar results. The overall five-year survival rate was significantly higher in the low CKS2 expression group (59.9%) than in the high CKS2 expression group (23.9%) (p<0.01). Univariate and multivariate analysis showed that CKS2 expression status was an independent prognostic factor (relative risk, 1.41; 95% confidence interval, 1.01-1.97; p<0.05). Moreover, the inhibition of cellular proliferation by CKS2-siRNA was observed in a gastric cancer cell line. CKS2 is one of the gastric cancerrelated genes that correlates with biological aggressiveness and poor prognosis of gastric cancer. Thus, CKS2 is a possible candidate gene for diagnosis, as well as targeted molecular diagnosis and therapy in gastric cancer.

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Section: Discussionsupporting

confidence: 82%

Clinicopathological and biological significance of CDC28 protein kinase regulatory subunit 2 overexpression in human gastric cancer

Tanaka

Matsuzaki

Mimori³

et al. 2011

Int J Oncol

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“…These studies show efficiency of this technology to distinguish tumor from normal colonic tissue and classify tumors according to their anatomic localization (16,17) and microsatellite status (17,18). Subsequent reports demonstrate abilities of gene expression profiles to determine molecular signature of metastatic disease in primary tumors (20,21) and predict therapy response and disease prognosis (22)(23)(24)(25). A primary objective of this study was to identify differentially expressed genes in colorectal cancer, to search for specific gene-expression patterns associated with colorectal cancer progression, especially with metastatic spread to the regional lymph nodes.…”

Section: Discussionmentioning

confidence: 99%

Significant overexpression of Hsp110 gene during colorectal cancer progression

Slabý

Sobková²,

Svoboda³

et al. 2009

Oncol Rep

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Abstract. Colorectal cancer (CRC) is one of the most frequent malignant diseases in the world. Metastatic spread of the cancer to the lymph nodes is a crucial factor for progression and therapeutic management of the disease. We analysed gene expression profiles of CRC patiens by lowdensity cancer-focused oligonucleotide microarrays to identify new predictive markers of the extent of the disease and for better understanding of CRC progression. Relative expression levels of 440 genes known to be involved in cancer biology were obtained by low-density oligonucleotide microarrays from 20 tumor samples. Statistical analysis of gene expression data identified 3 genes (HSP110, HYOU1 and TCTP) significantly up-regulated in primary tumors of patients who developed lymph node metastasis. We have shown, for the first time, that up-regulation HSP110 and HYOU1 expression is associated with lymph node involvement in CRC. We validated the differences in HSP110 expression in an independent group of 30 patients of all clinical stages by real-time PCR. We identified significant up-regulation of HSP110 expression in colorectal tumors compared to adjacent non-tumoral tissue (p<0.0003). We observed significant differences of HSP110 gene expression between metastatic and localized disease (p=0.031) and negative trend of HSP110 gene expression and overall survival of CRC patients. We suggest that HSP110 gene is a promising molecular predictor in CRC. IntroductionColorectal cancer (CRC) is one of the most frequent malignant diseases in the world. With the incidence rate ~78 per 100,000 people, the Czech Republic is a country with one of the highest incidence of CRC in the world and the highest in Europe (1). The prognosis of these patients depends largely on the extent of the disease and a possibility of curative surgical intervention which is feasible only in patients with disease limited to the primary tumor and regional lymph nodes. Spread of the cancer to lymph nodes has been considered a crucial factor for progression and further therapeutic management of the disease. While in the case of clinical stage I and IV, the prognostic significance of the TNM classification is evident, for the group of patients diagnosed at stages II (without dissemination to regional lymph nodes) and III (with dissemination to lymph nodes) the prognostic information of clinical stage is much lower. The fact, that 30% of patients with clinical stage II of CRC will progress within five years and only 45% of the patients with clinical stage III will reach a 5-year survival, although undergoing radical surgery, implies that recent staging of CRC based on TNM classification is not optimal and failed for a significant proportion of non-advanced CRC patients. This situation is caused by two factors: firstly, understaging of regional lymph node status for the reason of insufficient number of resected and/or examined lymph nodes, secondly, the TNM classification does not include biological characteristics and predictors of tumor behaviour. Multicentric studies ba...

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“…Overall, these studies and our work point to CKS2 as a robust marker associated with meningioma recurrence and malignant transformation. Cks2 is required for the first metaphase/anaphase transition of mammalian meiosis, and was also found to be upregulated in colon cancer metastases [33,34], prostate and gastric cancer [35,36], and hepatocellular carcinomas [37]. Recent data showed that gene expression of cyclin-dependent kinase subunit Cks2 is repressed by the tumor suppressor p53 [38].…”

Section: Discussionmentioning

confidence: 99%

DNA Microarray Analysis Identifies CKS2 and LEPR as Potential Markers of Meningioma Recurrence

Menghi¹,

Orzan²,

Eoli³

et al. 2011

The Oncologist

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Meningiomas are the most frequent intracranial tumors. Surgery can be curative, but recurrences are possible. We performed gene expression analyses and loss of heterozygosity (LOH) studies looking for new markers predicting the recurrence risk. We analyzed expression profiles of 23 meningiomas (10 grade I, 10 grade II, and 3 grade III) and validated the data using quantitative polymerase chain reaction (qPCR). We performed LOH analysis on 40 meningiomas, investigating chromosomal regions on 1p, 9p, 10q, 14q, and 22q. We found 233 and 268 probe sets to be significantly down-and upregulated, respectively, in grade II or III meningiomas. Genes downregulated in high-grade meningiomas were overrepresented on chromosomes 1, 6, 9, 10, and 14. Based on functional enrichment analysis, we selected LIM domain and actin binding 1 (LIMA1), tissue inhibitor of metalloproteinases 3 (TIMP3), cyclin-dependent kinases regulatory subunit 2 (CKS2), leptin receptor (LEPR), and baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) for validation using qPCR and confirmed their differential expression in the two groups of tumors. We calculated ⌬Ct values of CKS2 and LEPR and found that their differential expression (C-L index) was significantly higher in grade I than in grade II or III meningiomas (p < .0001). Interestingly, the C-L index of nine grade I meningiomas from patients who relapsed in <5 years was significantly lower than in grade I meningiomas from patients who did not relapse. These findings indicate that the C-L index may be relevant to define the progression risk in meningioma patients, helping guide their clinical management. A prospective analysis on a larger number of cases is warranted.

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Identification of gene signatures for invasive colorectal tumor cells

Cited by 55 publications

References 49 publications

Clinicopathological and biological significance of CDC28 protein kinase regulatory subunit 2 overexpression in human gastric cancer

Clinicopathological and biological significance of CDC28 protein kinase regulatory subunit 2 overexpression in human gastric cancer

Significant overexpression of Hsp110 gene during colorectal cancer progression

DNA Microarray Analysis Identifies CKS2 and LEPR as Potential Markers of Meningioma Recurrence

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