| 1. |
- Gao, Jingfang, et al.
(författare)
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RAD50/MRE11/NBS1 proteins in relation to tumour development and prognosis in patients with microsatellite stable colorectal cancer
- 2008
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Ingår i: Histology and Histopathology. - : Histology and Histopathology. - 0213-3911 .- 1699-5848. ; 23:12, s. 1495-1502
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Tidskriftsartikel (refereegranskat)abstract
- RAD50/MRE11/NBS1 complex is essential for DNA double-strand break repair and for maintaining genomic integrity. In this study, we immunohistochemically examined MRE11, NBS1 and RAD50 expression in primary CRCs (n = 208), the corresponding distant (n= 41) and adjacent normal mucosa ( n= 130), and lymph node metastases ( n= 26), and investigated their clinicopathological significance in colorectal cancers ( CRCs). We found that the intensity and percentage of MRE11 and NBS1 in primary CRCs were positively correlated with each other and with RAD50 (P < 0.0001). Strong expression of MRE11, NBS1 or combined RAD50/MRE11/NBS1 was related to MSS, positive hMLH1 expression, earlier tumour stage (TNM stage I and II) and favourable survival (P < 0.05). A high percentage of MRE11 expression was associated with less local recurrence and high apoptotic activity (P < 0.05). In MSS CRCs, the expression of MRE11 and NBS1 was stronger than that in normal mucosa (P < 0.05), and strong expression of NBS1 in primary tumour was related to favourable survival of patients in TNM stage I and II (univariate analysis: P = 0.03; multivariate analysis: P = 0.07). In MSI CRCs, neither MRE11 nor NBS1 expression showed differences among normal mucosa, primary tumour and metastasis, or among clinicopathological variables. In conclusion, RAD50/MRE11/NBS1 proteins interacted with each other, which had different clinicopathological significance in MSS and MSI CRCs, and further, each component of the complex might have additional roles. NBS1 might be a prognostic factor for patients with MSS tumour in TNM stage I and II.
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| 2. |
- Gnosa, Sebastian, et al.
(författare)
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Expression of AEG-1 mRNA and protein in colorectal cancer patients and colon cancer cell lines
- 2012
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Ingår i: Journal of Translational Medicine. - : BioMed Central. - 1479-5876. ; 10:109
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Tidskriftsartikel (refereegranskat)abstract
- Background: Astrocyte elevated gene 1 (AEG-1), an important oncogene, has been shown to be overexpressed in several types of cancers. In colorectal cancer (CRC), the protein level of AEG-1 is up-regulated in tumour tissue compared to normal mucosa, showing prognostic significance. Since little is known about the transcriptional level of AEG-1 expression and its biological pathway in CRC the aim of the present study was to examine the relationship of AEG-1 mRNA expression, the protein level and clinicopathological variables as well as its biology pathway in CRC. less thanbrgreater than less thanbrgreater thanMaterial and methods: The mRNA expression of AEG-1 was analysed by qPCR in fresh frozen patient samples including 156 primary tumours, along with the corresponding normal mucosa, and in five colon cancer cell lines, SW480, SW620, KM12C, KM12SM and KM12L4a. AEG-1 protein expression was investigated by immunohistochemistry in paraffin-embedded materials from 74 distant normal mucosa, 107 adjacent mucosa, 158 primary tumour, 35 lymph node metastasis and 9 liver metastasis samples. In addition, the AEG-1 protein expression was elucidated in the cell lines by Western blot. less thanbrgreater than less thanbrgreater thanResults: The lymph node metastatic cell line SW620 had a significantly higher AEG-1 mRNA (0.27 +/- 0.02) expression compared to the primary tumour cell line SW480 (0.17 +/- 0.04, p = 0.026). AEG-1 expression at the mRNA level and/or the protein level was significantly up-regulated gradually from normal mucosa to primary CRC, and then to lymph node metastasis and finally to liver metastasis (p andlt; 0.05). There were significant associations of AEG-1 mRNA expression with tumour location (p = 0.047), as well as mRNA and protein expression with the tumour stage (p andlt; 0.03). Furthermore AEG-1 protein expression was positively related to biological variables including NF-kappa B, p73, Rad50 and apoptosis (p andlt; 0.05). less thanbrgreater than less thanbrgreater thanConclusion: AEG-1 is up-regulated, at the mRNA and the protein level, during CRC development and aggressiveness, and is related to tumour location and stage. It may play its role in CRC through the NF-kappa B signaling pathway.
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| 3. |
- Lewander, Andreas, et al.
(författare)
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NF-kappa B p65 phosphorylated at serine-536 is an independent prognostic factor in Swedish colorectal cancer patients
- 2012
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Ingår i: International Journal of Colorectal Disease. - : Springer. - 0179-1958 .- 1432-1262. ; 27:4, s. 447-452
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Tidskriftsartikel (refereegranskat)abstract
- The NF-kappa B transcription factor protein family has diverse cellular and biological functions, and posttranslational modification is important to regulate these functions. An important site of phosphorylation of NF-kappa B p65 subunit is at serine-536 (phospho-Ser536-p65), and this phosphorylation is involved in regulation of transcriptional activity, nuclear localization, and protein stability. In this study, we investigated expression of phospho-Ser536-p65 in colorectal cancers and its relationships with clinicopathological factors. The expression of phospho-Ser536-p65 was examined by immunohistochemistry in 203 primary colorectal cancers, 156 normal mucosa specimens, and 18 metastases in the lymph nodes. The expression of phospho-Ser536-p65 increased from normal mucosa to primary tumor (p < 0.0001). Further, the increased expression of phospho-Ser536-p65 in the cytoplasm of the primary tumors correlated with worse survival of the patients independently of gender, age, tumor location, stage, and differentiation (p = 0.04; hazard ratio, 1.89; 95% CI 1.03-3.47). The NF-kappa B p65 subunit phosphorylated at serine-536 is an independent prognostic factor in colorectal cancer patients.
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| 4. |
- Shen, Yang-mei, et al.
(författare)
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Novel gene hBiot2 is an independent prognostic factor in colorectal cancer patients
- 2012
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 27:2, s. 376-382
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Tidskriftsartikel (refereegranskat)abstract
- The present study investigated the expression of the novel gene hBiot2 in colorectal cancer (CRC) and its relationships with clinicopathological variables in CRC patients. The expression of hBiot2 in 163 primary CRCs together with the corresponding normal mucosa, 36 liver metastases and 5 colon cancer cell lines was examined using real-time PCR. In situ hybridization (ISH) was performed to evaluate the localization of hBiot2 expression in CRC and normal mucosa. hBiot2 expression at the RNA level was localized in the nucleus of tumor cells and normal epithelial cells. The mean expression of hBiot2 in the CRCs (243.571 +/- 564.569) was higher compared to the normal mucosa (107.252 +/- 413.635, Pandlt;0.0001) and liver metastasis samples (42.002 +/- 40.809, P=0.0002). hBiot2 expression was increased from stages I + II to III (P=0.047), and no difference in the expression was found in stages III and IV (P=0.452). A high value of hBiot2 was associated with a poorer prognosis compared with a low value independently of gender, age, tumor site, stage and differentiation (P=0.007, RR 7.519, 95% Cl 1.729-32.704). Liver metastasis, smaller tumors, non-local recurrence and primary liver surgery alone were associated with a higher value of hBiot2 compared to larger tumors, local recurrence and repeated liver surgery (P=0.003, 0.044 and 0.026, respectively). An inverse relationship was found between hBiot2 expression and the metastatic potential of the colon cancer cell lines. Thus, increased expression of hBiot2 may be an early and interim event in the development of CRC. A higher expression of hBiot2 in primary CRC patients independently indicates a poorer prognosis.
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| 5. |
- Widegren, Emma, et al.
(författare)
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Expression of FXYD3 Protein in Relation to Biological and Clinicopathological Variables in Colorectal Cancers
- 2009
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Ingår i: Chemotherapy. - : S. Karger AG. - 0009-3157 .- 1421-9794. ; 55:6, s. 407-413
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Tidskriftsartikel (refereegranskat)abstract
- Background: FXYD3 is up-/down-regulated in different types of cancers. We examined FXYD3 expression in colorectal cancers and its relationship to biological and clinicopathological variables. Patients and Methods: Expression of FXYD3 protein was immunohistochemically examined in distant normal mucosa (n = 34), adjacent normal mucosa (n = 72), primary tumour (n = 150) and lymph node metastasis (n = 35) from colorectal cancer patients. Results: FXYD3 was highly expressed in primary tumour compared to adjacent normal mucosa (p = 0.02). FXYD3 was or tended to be positively related to the expression of ras (p = 0.02), p53 (p = 0.06), legumain (p = 0.02) and proliferating cell nuclear antigen (p = 0.03). Moreover, there was a higher frequency of strong FXYD3 expression in Dukes A-C tumours than in D tumours (p = 0.04). The strong FXYD3 expression tended to predict worse survival in the patients with Dukes A + B tumour (p = 0.07), while there was no such tendency in the patients with Dukes C + D tumour (p = 0.94). The tumours located in the colon had a higher degree of FXYD3 expression than the tumours located in the rectum (p = 0.05). Conclusion: The FXYD3 was associated with certain biological variables and may be involved in the development of the relative earlier stages of colorectal cancers.
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