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Reduced NKX2.1 expression predicts poor prognosis of gastric carcinoma.

Zhao BW, Jiang SS, Chen YM, Huang CY, Li YF - PLoS ONE (2014)

Bottom Line: Thyroid transcription factor-1 (NKX2.1/TITF-1) is a member of the thyroid tissue-specific transcription factor family that has been proven to be closely associated with many human diseases.Recently, it was reported that NKX2.1 expression is lost or reduced in some human cancers such as lung cancer and thyroid cancer.Our qRT-PCR results showed that the expression of NKX2.1 mRNA was reduced in tumor tissue samples compared with that in matched adjacent non-tumor tissue samples (P < 0.001); this finding was confirmed by Western blot analysis (P < 0.001).

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oncology in Southern China and Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China; Department of Gastric & Pancreatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.

ABSTRACT
Thyroid transcription factor-1 (NKX2.1/TITF-1) is a member of the thyroid tissue-specific transcription factor family that has been proven to be closely associated with many human diseases. Recently, it was reported that NKX2.1 expression is lost or reduced in some human cancers such as lung cancer and thyroid cancer. However, there was insufficient data to suggest that NKX2.1 functionality could be used as a prognostic factor. Therefore, this study aims to investigate NKX2.1 expression and its prognostic significance in primary gastric carcinoma. Then, we attempted to investigate if NKX2.1 expression was related to the clinicopathological characteristics and prognosis of gastric carcinoma (GC)patients. The expression levels of NKX2.1 were analyzed in tissue samples from 205 gastric carcinoma patients by real-time quantitative PCR (qRT-PCR), Western blotting, and immunohistochemical staining(IHC). Our qRT-PCR results showed that the expression of NKX2.1 mRNA was reduced in tumor tissue samples compared with that in matched adjacent non-tumor tissue samples (P < 0.001); this finding was confirmed by Western blot analysis (P < 0.001). Our immunohistochemical staining data indicated that NKX2.1 expression was significantly decreased in 87 of 205 (42.4%) gastric carcinoma cases. Kaplan-Meier survival curves revealed that the decreased expression of NKX2.1 was significantly associated with poor prognosis in gastric carcinoma patients (P < 0.001). Multivariate Cox analysis identified NKX2.1 expression as an independent prognostic factor for overall survival (P = 0.005). Furthermore, the functions of Nkx2.1 were analyzed with respect to the proliferation, migration, and invasion of GC cell lines. Our data suggest that NKX2.1 may function as a tumor suppressor in primary gastric carcinoma and that its reduced expression independently predicts an unsatisfactory prognosis in gastric carcinoma patients.

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The NKX2.1 protein levels were significantly lower, (A), in the SGC-7901 and higher in the MPC-803 and HGC-27 cell lines than in the normal gastric cell line GES.(B) The NKX2.1 expression was significantly higher in the NKX2.1 transfected SGC-7901 cells and lower in the siNKX2.1 transfected MPC-803/HGC-27 cells than controls. (C-E) The MTS assay showed that NKX2.1 suppressed the proliferation of the over-expressed SGC-7901 and accelerated the proliferation of the down-regulated MPC-803/HGC-27 cells, * P < 0.05.
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pone-0114556-g005: The NKX2.1 protein levels were significantly lower, (A), in the SGC-7901 and higher in the MPC-803 and HGC-27 cell lines than in the normal gastric cell line GES.(B) The NKX2.1 expression was significantly higher in the NKX2.1 transfected SGC-7901 cells and lower in the siNKX2.1 transfected MPC-803/HGC-27 cells than controls. (C-E) The MTS assay showed that NKX2.1 suppressed the proliferation of the over-expressed SGC-7901 and accelerated the proliferation of the down-regulated MPC-803/HGC-27 cells, * P < 0.05.

Mentions: To evaluate the effect of NKX2.1 on cell proliferation a NKX2.1 expression vector and a GFP-control vector were transfected into SGC-7901 cell lines. The efficiencies of transfection were detected by western blotting (Figure 5B). A cell growth assay revealed that cell growth rates in NKX2.1-transfected cell lines were slower than GFP-transfected gastric cancer cell lines (Figure 5C). The overexpression of NKX2.1 dramatically reduced the migration and invasion ability of the cells (Figure 6).


Reduced NKX2.1 expression predicts poor prognosis of gastric carcinoma.

Zhao BW, Jiang SS, Chen YM, Huang CY, Li YF - PLoS ONE (2014)

The NKX2.1 protein levels were significantly lower, (A), in the SGC-7901 and higher in the MPC-803 and HGC-27 cell lines than in the normal gastric cell line GES.(B) The NKX2.1 expression was significantly higher in the NKX2.1 transfected SGC-7901 cells and lower in the siNKX2.1 transfected MPC-803/HGC-27 cells than controls. (C-E) The MTS assay showed that NKX2.1 suppressed the proliferation of the over-expressed SGC-7901 and accelerated the proliferation of the down-regulated MPC-803/HGC-27 cells, * P < 0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4257675&req=5

pone-0114556-g005: The NKX2.1 protein levels were significantly lower, (A), in the SGC-7901 and higher in the MPC-803 and HGC-27 cell lines than in the normal gastric cell line GES.(B) The NKX2.1 expression was significantly higher in the NKX2.1 transfected SGC-7901 cells and lower in the siNKX2.1 transfected MPC-803/HGC-27 cells than controls. (C-E) The MTS assay showed that NKX2.1 suppressed the proliferation of the over-expressed SGC-7901 and accelerated the proliferation of the down-regulated MPC-803/HGC-27 cells, * P < 0.05.
Mentions: To evaluate the effect of NKX2.1 on cell proliferation a NKX2.1 expression vector and a GFP-control vector were transfected into SGC-7901 cell lines. The efficiencies of transfection were detected by western blotting (Figure 5B). A cell growth assay revealed that cell growth rates in NKX2.1-transfected cell lines were slower than GFP-transfected gastric cancer cell lines (Figure 5C). The overexpression of NKX2.1 dramatically reduced the migration and invasion ability of the cells (Figure 6).

Bottom Line: Thyroid transcription factor-1 (NKX2.1/TITF-1) is a member of the thyroid tissue-specific transcription factor family that has been proven to be closely associated with many human diseases.Recently, it was reported that NKX2.1 expression is lost or reduced in some human cancers such as lung cancer and thyroid cancer.Our qRT-PCR results showed that the expression of NKX2.1 mRNA was reduced in tumor tissue samples compared with that in matched adjacent non-tumor tissue samples (P < 0.001); this finding was confirmed by Western blot analysis (P < 0.001).

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oncology in Southern China and Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China; Department of Gastric & Pancreatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.

ABSTRACT
Thyroid transcription factor-1 (NKX2.1/TITF-1) is a member of the thyroid tissue-specific transcription factor family that has been proven to be closely associated with many human diseases. Recently, it was reported that NKX2.1 expression is lost or reduced in some human cancers such as lung cancer and thyroid cancer. However, there was insufficient data to suggest that NKX2.1 functionality could be used as a prognostic factor. Therefore, this study aims to investigate NKX2.1 expression and its prognostic significance in primary gastric carcinoma. Then, we attempted to investigate if NKX2.1 expression was related to the clinicopathological characteristics and prognosis of gastric carcinoma (GC)patients. The expression levels of NKX2.1 were analyzed in tissue samples from 205 gastric carcinoma patients by real-time quantitative PCR (qRT-PCR), Western blotting, and immunohistochemical staining(IHC). Our qRT-PCR results showed that the expression of NKX2.1 mRNA was reduced in tumor tissue samples compared with that in matched adjacent non-tumor tissue samples (P < 0.001); this finding was confirmed by Western blot analysis (P < 0.001). Our immunohistochemical staining data indicated that NKX2.1 expression was significantly decreased in 87 of 205 (42.4%) gastric carcinoma cases. Kaplan-Meier survival curves revealed that the decreased expression of NKX2.1 was significantly associated with poor prognosis in gastric carcinoma patients (P < 0.001). Multivariate Cox analysis identified NKX2.1 expression as an independent prognostic factor for overall survival (P = 0.005). Furthermore, the functions of Nkx2.1 were analyzed with respect to the proliferation, migration, and invasion of GC cell lines. Our data suggest that NKX2.1 may function as a tumor suppressor in primary gastric carcinoma and that its reduced expression independently predicts an unsatisfactory prognosis in gastric carcinoma patients.

Show MeSH
Related in: MedlinePlus