ABSTRACT
Lymph node metastasis remains a key factor that affects the prognosis of patients with colon cancer. The aim of the present study was to identify and evaluate serum metabolites as biomarkers for the detection of tumor lymph node metastasis and the prediction of patient survival. The present study analyzed the metabolites in the serum of patients with advanced colon cancer both with and without lymph node metastasis. Blood samples from 104 patients with stage T3 colon cancer were collected and analyzed using liquid chromatography-mass spectrometry. The metabolites were structurally confirmed with data from the Human Metabolome Database. The association between the serum metabolites and the clinicopathological characteristics and survival time of patients from the present study was analyzed. Overall, 227 different metabolites were identified in the serum of patients with stage T3 colon cancer with or without lymph node metastasis. Furthermore, 17 of these metabolites may potentially distinguish those patients with lymph node metastasis from those patients without. In addition, five factors, including abscisic acid, calcitroic acid and glucosylsphingosine presence in the serum, age and sex, were identified as independent predictors for lymph node metastasis (P<0.05). Furthermore, three factors, including abscisic acid, calcitroic acid and glucosylsphingosine presence in the serum were independent predictors for patient survival (P<0.05). In conclusion, the serum levels of abscisic acid, calcitroic-acid and glucosylsphingosine may be considered as potential biomarkers to predict the occurrence of lymph node metastasis and the survival time of patients with colon cancer.
ABSTRACT
Numerous studies have proved that microRNAs (miRNAs) play crucial roles in the tumorigenesis and progression of gastric cancer (GC). Our study was to investigate the correlation between miR-338-3p expression and clinical features as well as prognosis of GC. A total of 138 GC tissue specimens and adjacent non-cancerous tissues were collected for further analysis, then quantitative PCR method was used to detect the relative miR-338-3p expression. Our study showed that tissue miR-338-3p level was greatly decreased in cancer tissues compared with paired normal tissues. Furthermore, loss of tissue miR-338-3p was positively associated with aggressive clinical characteristics (advanced clinical stage, poorer differentiation and lymph node invasion), shorter overall survival and recurrence free survival. Finally, tissue miR-338-3p expression was confirmed to be an independent prognostic factor for GC. Overall, our findings indicate that miR-338-3p acts as a tumor suppressor in GC and tissue miR-338-3p might serve as a novel prognostic biomarker of GC.
Subject(s)
Down-Regulation , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Stomach Neoplasms/genetics , Aged , Biomarkers, Tumor/genetics , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Prognosis , Stomach Neoplasms/diagnosisABSTRACT
BACKGROUND: An overwhelming amount of evidence has emerged suggesting that dysregulated microRNAs (miRNAs) play crucial roles in tumorigenesis. OBJECTIVE: The study was to analyze tissue/serum miR-144 expression in gastric cancer and then evaluate their potential to predict the prognosis of gastric cancer. METHODS: We examined miR-144 levels in tissues and peripheral blood samples from 96 gastric cancer patients using real-time PCR. Then the association between tissue/serum miR-144 levels and clinicopathological parameters was determined. RESULTS: The expression levels of miR-144 were significantly down-regulated in the cancerous tissue and serum samples from gastric cancer patients. Serum miR-144 was able to differentiate the gastric cancer patients from healthy controls with high accuracy. In addition, tissue and serum miR-144 levels were both associated with clinical stage and lymph node metastasis. Moreover, patients with lower tissue or serum miR-144 suffered worse 5 year overall survival and disease free survival. CONCLUSIONS: Taken together, our data support the potential clinical value of tissue and serum miR-144 as prognostic biomarkers in gastric cancer.
Subject(s)
Biomarkers, Tumor , Gene Expression , MicroRNAs/genetics , Stomach Neoplasms/genetics , Stomach Neoplasms/mortality , Adult , Aged , Circulating MicroRNA , Female , Humans , Male , MicroRNAs/blood , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Prognosis , ROC Curve , Stomach Neoplasms/diagnosis , Stomach Neoplasms/therapy , Tumor BurdenABSTRACT
Understanding how colorectal cancer escapes from immunosurveillance and immune attack is important for developing novel immunotherapies for colorectal cancer. In this study we evaluated the role of canonical Wnt signaling in the regulation of T cell function in a mouse colorectal cancer model. We found that colorectal cancer cells expressed abundant Wnt ligands, and intratumoral T cells expressed various Frizzled proteins. Meanwhile, both active ß-catenin and total ß-catenin were elevated in intratumoral T cells. In vitro study indicated that colorectal cancer cells suppressed IFN-γ expression and increased IL-17a expression in activated CD4+ T cells. However, the cytotoxic activity of CD8+ T cells was not altered by colorectal cancer cells. To further evaluate the importance of Wnt signaling for CD4+ T cell-mediated cancer immunity, ß-catenin expression was enforced in CD4+ T cells using lentiviral transduction. In an adoptive transfer model, enforced expression of ß-catenin in intratumoral CD4+ T cells increased IL-17a expression, enhanced proliferation and inhibited apoptosis of colorectal cancer cells. Taken together, our study disclosed a new mechanism by which colorectal cancer impairs T cell immunity.
