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.

Protein/nucleic acid deglycase DJ‑1 (DJ‑1) is a 20‑kDa conserved protein, which belongs to the DJ‑1/ThiJ/Pfp Ⅰ protein superfamily. Immunohistochemistry was performed to investigate the expression of DJ‑1 in a colorectal cancer (CRC) tissue microarray containing tumor and corresponding adjacent normal tissues. In the present study, DJ‑1 expression was significantly upregulated in CRC cells and tissues, compared with that in normal colon cells and adjacent normal tissues, respectively. In addition, patients with high DJ‑1 expression levels had a worse overall survival (OS) compared with patients with low expression levels. Multivariate Cox regression analysis revealed that high DJ‑1 expression levels was an independent prognostic factor for patients with CRC. Moreover, DJ‑1 was able to regulate the PI3K/Akt/p27/cyclin E and PI3K/Akt/mTOR signaling pathways to promote CRC cell growth and metastasis in vitro and in vivo. In addition, DJ‑1 regulated the NF‑κB/Snail signaling pathway to induce CRC cell epithelial‑mesenchymal transition to promote migration and invasion. Notably, patients receiving LFP treatment (oxaliplatin, 5‑FU and tetrahydrofolate) had an increased OS compared with patients who underwent only surgery and low DJ‑1 expression levels. The findings from the present study suggest that DJ‑1 may serve as a promising prognostic marker and predicts chemotherapy efficacy in patients with CRC.

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.

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. Result...

Background: Cisplatin-based treatment often leads to therapeutic failure because the acquisition of cisplatin resistance. The combination of cisplatin with other agents has been recognized as a promising strategy to overcome cisplatin resistance. Objective: Celastrus orbiculatus is a traditional Chinese medicine from Celastraceae family with multiple pharmacological activities. We previously found that the ethyl acetate extract of Celastrus orbiculatus (COE) exhibited significant antitumor activity in gastric cancer. Here, we asked whether COE could increase the sensitivity of cisplatin. Methods: We use CCK8 assay to show synergistic cytotoxicity of COE and cisplatin. Then, PI single staining and FITC-Annexin V/PI double staining were used to observe apoptotic cells through flow cytometry. The proteins of caspase signaling pathway were examined by Western blotting. Results: COE and cisplatin showed synergistic cytotoxicity in a dose-dependent manner in BGC 823 and SGC 7901 gastric cancer cells, and COE could increase the number of apoptotic cells upon cisplatin treatment in vitro. Moreover, our results indicated that COE could enhance cisplatin–induced activation of caspase-8 or caspase- 9/caspase-3/PARP1 signaling pathways. The xenograft study further confirmed that COE increased the sensitivity of cisplatin in vivo. Conclusion: Our findings provided new evidence that COE could increase the sensitivity of cisplatin on the antitumor effect.

Metastasis is the main cause of poor prognosis of patients with gastric cancer (GC). Thus, current research is focused on identifying biomarkers that can predict the prognosis of patients with GC. C‑X‑C motif chemokine receptor 4 (CXCR4) and vascular endothelial growth factor (VEGF) have been reported to play important roles in different types of malignancies; however, their role in the prognosis of GC remains unknown. The present study aimed to investigate the potential role of CXCR4 and VEGF in predicting the prognosis of patients with GC. Immunohistochemistry analysis was performed to analyze the expression levels of CXCR4 and VEGF in a GC tissue microarray containing GC tissues and adjacent normal tissues. The association between CXCR4 or VEGF expression levels and the clinicopathological characteristics or survival outcomes were assessed. Furthermore, Transwell and wound healing assays were performed to determine the cell invasive and migratory abilities in vitro. The results demonstrated that CXCR4 promoted AGS cell invasion and migration by regulating VEGF expression. In addition, CXCR4 and VEGF expression levels were significantly upregulated in GC tissues compared with adjacent normal tissues, which was associated with a poorer overall survival (OS). Cox regression analysis demonstrated that both upregulated CXCR4 and VEGF expression were independent negative biomarkers of OS. To the best of our knowledge, the present study was the first to discover that CXCR4 and VEGF exert synergistic roles as efficient prognostic indicators for patients with GC.