ABSTRACT
Aim: Gastric cancer (GC) is one of the most common malignant tumors in the world. It is important to find accurate and reliable biomarkers in order to decrease whole morbidity and mortality. Results: We examined the expression of COX-2 and mTOR on GC tissue microarrays by immunohistochemistry. Multivariate COX regression analysis showed that the expression of COX-2 or mTOR was an independent factor in the prognosis of GC patients. In addition, COX-2 and mTOR have a potentially synergistic effect on predicting the prognosis of GC. Conclusion: The combined expression of COX-2 and mTOR could serve as efficient prognostic indicators and COX-2 could suppress GC metastasis via regulating mTOR.
Subject(s)
Cyclooxygenase 2/metabolism , Stomach Neoplasms/diagnosis , Stomach Neoplasms/pathology , TOR Serine-Threonine Kinases/metabolism , Aged , Cell Line, Tumor , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Neoplasm Metastasis , Prognosis , Stomach Neoplasms/metabolism , Survival AnalysisABSTRACT
CHIP and Galectin-1 are associated with the development of metastasis in cancer. However, the precise roles of CHIP or Gal1 in colorectal cancer are uncertain. Here, our study explored the relationship and clinical significance of CHIP or Gal1 in CRC. CHIP or Gal1 expression was significantly decreased or up-regulated in CRC compared with adjacent noncancerous tissues by immunohistochemistry on a CRC tissue microarray, respectively. Low CHIP or high Gal1 expression significantly correlated with clinicopathological characteristics in patients, as well as with shorter overall survival. Multivariate Cox regression analysis revealed that CHIP or Gal1 expression was an independent prognostic factor for CRC patients. Moreover, CHIP associated with Gal1 has a synergistic effect on the prediction of CRC prognosis. In vitro and vivo, high CHIP or low Gal1 expression inhibit CRC growth or metastasis. Our results found that CHIP could degradate Gal1 by ubiquitination. In summary, CHIP could inhibit CRC growth or metastasis through promoting Gal1 ubiquitination and degradation by proteasome. CHIP and Gal1 expressions are novel candidate prognostic markers in CRC. A combined effect of CHIP and Gal1 as efficient prognostic indicators was found for the first time.
Subject(s)
Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Galectin 1/metabolism , Ubiquitin-Protein Ligases/metabolism , Aged , Colorectal Neoplasms/genetics , Female , Galectin 1/genetics , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Ubiquitin-Protein Ligases/genetics , Ubiquitination/genetics , Ubiquitination/physiologyABSTRACT
Colorectal cancer has a common cause of morbidity and mortality. Therefore, it is urgent to detect reliable biomarkers to predict prognosis in CRC. Here, we determined the expression of TIMP-2 and MMP-9 in a CRC tissue microarray by immunohistochemistry. We found that lower TIMP-2 or/and higher MMP-9 expression in cancer tissues was correlated with poorer overall survival (OS). TIMP-2 or MMP-9 expression was independent prognostic factors for CRC. Furthermore, TIMP-2 and MMP-9 expression had a synergistic role as efficient prognostic indicators for CRC patients. In vitro and in vivo, TIMP-2 could inhibit HCT 116 cells invasion and migration by regulating MMP-9. In sum, a combined expression of TIMP-2 and MMP-9 as efficient prognostic indicators was found for the first time.
