DCK is an Unfavorable Prognostic Biomarker and Correlated With Immune Infiltrates in Liver Cancer.

BACKGROUND: The biological function of deoxycytidine kinase in tumor is not yet clear, and there are a few studies relating to the correlation of deoxycytidine kinase gene with the occurrence and development of liver cancer. METHODS: The messenger RNA expression of deoxycytidine kinase was analyzed with the use of the UALCAN and GEPIA database. Moreover, we assessed the function of deoxycytidine kinase on clinical prognosis with Kaplan-Meier plotter database. The relationship between deoxycytidine kinase and cancer immune infiltrates was investigated via Tumor Immune Estimation Resource site. Furthermore, Tumor Immune Estimation Resource was also used to evaluate the correlations between the expression of deoxycytidine kinase and gene marker sets of immune infiltrates. RESULTS: The deoxycytidine kinase messenger RNA level significantly upregulated in patients with liver cancer compared to normal liver samples. Moreover, the increased expression of deoxycytidine kinase messenger RNA was closely associated with reduced overall survival and disease-free survival in all liver cancers. In addition, deoxycytidine kinase expression displayed a strong correlation with infiltrating levels of macrophages, neutrophils, and dendritic cells in liver cancer, and deoxycytidine kinase expression was positively correlated with diverse immune marker sets in liver cancer. CONCLUSIONS: All the above findings suggested that increased expression of deoxycytidine kinase was significantly related to unfavorable prognosis in patients with liver cancer. And deoxycytidine kinase is correlated with immune infiltrating levels, including those of B cells, macrophages, neutrophils, and dendritic cells in patients with liver cancer. These findings suggest that deoxycytidine kinase can be used as a prognostic biomarker for determining prognosis and immune infiltration in liver cancer. And deoxycytidine kinase is a potential target for liver cancer therapy, and these preliminary findings require further study to determine whether deoxycytidine kinase-targeting reagents might be developed for clinical application in liver cancer.

miR-30b suppresses the progression of breast cancer through inhibition of the PI3K/Akt signaling pathway by targeting Derlin-1.

BACKGROUND: MicroRNAs (miRNAs) play an essential role in the initiation, progression and metastasis of breast cancer. It has been confirmed that miR-30b is involved in various cancers. However, the specific involvement of miR-30b on breast cancer metastasis remains unknown. In the current study, we aimed to investigate the role of miR-30b in the progression and metastasis of breast cancer in vitro. METHODS: We up-regulated the expression of miR-30b in breast cancer cell lines SKBR3 and MDA-MB-231 by transfecting pCMV-miR-30b vector. CCK8, colony formation, Transwell, and flow cytometry assays were used to examine cell proliferation, migration, invasion and apoptosis, respectively. A dual-luciferase reporter assay was performed to identify the relationship between miR-30b and the target gene. Western blot assay was used to detect related proteins. RESULTS: Our data showed that the overexpression of miR-30b significantly inhibited proliferation, migration and invasion abilities in SKBR3 and MDA-MB-231 cells. Meanwhile, overexpression of miR-30b induced cell apoptosis for both SKBR3 and MDA-MB-231 cells by regulating the expression of apoptosis-related proteins (Bcl-2, Bax, active Caspase-3, and Caspase-9). Moreover, miR-30b inhibited the activation of the PI3K/Akt signaling pathway by decreasing the phosphorylation levels of Akt and mTOR. Furthermore, we determined that miR-30b could down-regulate the expression of Derlin-1 in a post-transcriptional manner by employing the dual-luciferase reporter and western blot assays. Further analysis demonstrated that depletion of Derlin-1 inhibited Akt phosphorylation, and Derlin-1 could restore the effect of miR-30b on Akt. In addition, the CCK8 assay showed that Derlin-1 could partly reverse the inhibition of cell proliferation of SKBR3 and MDA-MB-231 cells mediated by miR-30b. CONCLUSIONS: Our data demonstrated that miR-30b suppresses the progression and metastasis of breast cancer via inhibition of the PI3K/Akt signaling pathway by targeting Derlin-1 in vitro. This suggests that miR-30b might be a novel potent target for breast cancer therapy.

New utility of an old marker: serum low-density lipoprotein predicts histopathological response of neoadjuvant chemotherapy in locally advanced gastric cancer.

BACKGROUND: Although the correlation between metabolic abnormality and gastric cancer has been extensively investigated, the question of whether metabolic parameters might influence the efficacy of chemotherapy in locally advanced gastric cancer is still unanswered. In our present study, we investigated the relationship between serum fasting glucose, lipid levels, and histopathological response of neoadjuvant chemotherapy (NAC) in locally advanced gastric cancers. PATIENTS AND METHODS: A total of 128 patients were identified from a prospectively maintained database of patients with locally advanced gastric cancer who received NAC between July 2004 and December 2012. Histopathological response after NAC was analyzed according to Becker's tumor-regression grade. Univariate analyses and multivariable regression analyses were performed to determine the correlation between tumor size, differentiation, fasting glucose, lipid levels, and tumor histopathological response after NAC. RESULTS: Univariate analysis revealed that low-density lipoprotein level and total cholesterol, as well as tumor size and differentiation, correlated significantly with histopathological response. Low-density lipoprotein levels and tumor size were found to be independent predictors for histopathological response, according to multivariable regression analyses. CONCLUSION: In this observational, hypothesis-generating study, serum low-density lipoprotein measurement was found to be useful in predicting chemosensitivity to locally advanced gastric cancer patients undergoing NAC. Incorporation of serum low-density lipoprotein levels into individualized treatment protocols could be considered in clinical practice.

The relationship between Lin28 and the chemotherapy response of gastric cancer.

OBJECTIVE: The aim of the study reported here was to identify whether a stem cell biomarker, Lin28, may predict the pathologic tumor response to neoadjuvant chemotherapy for patients with locally advanced gastric cancer. METHODS: The study enrolled 47 patients with gastric cancer who underwent neoadjuvant chemotherapy followed by surgery between July 2004 and March 2012. Cancer tissue was biopsied by gastroscopy and Lin28 expression in the tissue was measured by immunohistochemistry. Statistical analyses were performed to identify the relationship between Lin28 expression and tumor regression grade. RESULTS: Of the 47 cases, pathologic nonresponse was observed in 29 (61.7%) and pathologic response in 18 (38.3%). Receiver-operating characteristic curve analysis showed that the histoscore of Lin28 expression with 0.325 as a cutoff value could differentiate between pathologic response and nonresponse. Multivariable analysis showed that Lin28 expression was an independent predictive factor for pathologic response to neoadjuvant chemotherapy (P = 0.006). CONCLUSION: Lin28 expression was associated with pathologic tumor response in locally advanced gastric cancer patients undergoing neoadjuvant chemotherapy. This may suggest that Lin28 can serve as a predictive biomarker for neoadjuvant chemotherapy in patients with gastric cancer.