Diagnostic values of MMP-7, MMP-9, MMP-11, TIMP-1, TIMP-2, CEA, and CA19-9 in patients with colorectal cancer.

OBJECTIVE: Colorectal cancer (CRC) is one of the most common and lethal malignancies. The identification of precise and noninvasive biomarkers is urgently needed to aid the early diagnosis and clinical management of CRC. METHODS: A total of 112 patients with CRC and 115 healthy control subjects were included in this study. Serum levels of matrix metalloproteinase (MMP)-7, MMP-9, MMP-11, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 were analyzed by enzyme-linked immunosorbent assay, and carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9 levels were measured using an automatic immunoassay analyzer. RESULTS: MMP-7, MMP-9, MMP-11, TIMP-1, TIMP-2, CEA, and CA19-9 levels were all significantly higher in CRC patients compared with healthy controls. MMP-7, TIMP-1, and CEA levels were also closely related to clinicopathologic features in patients with CRC. The combination of serum CEA, MMP-7, and TIMP-1 significantly improved the diagnostic value compared with any single marker (area under the curve 0.858-0.890). Furthermore, a combined detection model including MMP-7, TIMP-1, and CEA improved both the specificity and sensitivity for detecting CRC. CONCLUSIONS: The results showed that combined detection of CEA, MMP-7, and TIMP-1 in serum could provide a specific and sensitive biomarker for the diagnosis of CRC.

Changing Patterns in Clinicopathological Characteristics of Breast Cancer and Prevalence of BRCA Mutations: Analysis in a Rural Area of Southern China.

PURPOSE: Although the burden of breast cancer remains especially high in rural China, data on the clinicopathological characteristics and prevalence of the breast cancer susceptibility gene 1/2 (BRCA1/2) mutations in patients with breast cancer remain limited. We investigated the clinicopathological characteristics, changing patterns, and prevalence of BRCA1/2 mutations in patients with breast cancer. PATIENTS AND METHODS: The clinicopathological characteristics of 3712 women with pathologically confirmed primary breast cancer treated at Meizhou People's Hospital between January 2005 and December 2018 were evaluated. The prevalence of BRCA1/2 mutations in 340 patients with breast cancer diagnosed between January 2017 and September 2018 was also evaluated. RESULTS: The median age at diagnosis was 49±10.5 (range, 20-94) years. Positivity for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) was observed in 59.0%, 52.5%, and 24.9% of patients, respectively. Time trend analysis revealed that an increasing trend was observed for age at diagnosis (p = 0.001), proportion of patients without a reproductive history (p < 0.001), postmenopausal patients (p = 0.001), invasive pathological cancer type (p = 0.008), ER-positive rate (p < 0.001), PR-positive rate (p = 0.008), and HER2-positive rate (p < 0.001). Compared with patients without BRCA1/2 mutations, those with BRCA1/2 mutations were more likely to have a family history of breast or ovarian cancer (p < 0.001) and have triple-negative breast cancer (TNBC) (p < 0.001). Family history of breast or ovarian cancer (odds ratio [OR], 103.58; 95% confidence interval [CI], 20.58-521.45; p < 0.001) and TNBC subtype (OR, 5.97; 95% CI, 1.16-30.90; p = 0.033) were independent predictors for BRCA1/2 mutation. CONCLUSION: The clinicopathological characteristics of patients with breast cancer in this rural area have changed during the past decade. BRCA1/2 testing should be performed in patients with breast cancer with a family history of breast or ovarian cancer and TNBC.

Detection of critical genes associated with poor prognosis in breast cancer via integrated bioinformatics analyses.

PURPOSE: To explore the potential prognostic differentially expressed genes (DEGs) in breast cancer (BC) via bioinformatic analysis and elucidate possible mechanisms underlying the effects on BC progression. METHODS: Three datasets (GSE21422, GSE31192 and GSE42568) were extracted from Gene Expression Omnibus (GEO) information bank. The GEO2R tool and Venn diagram softwares were used for data filtration, GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis method were used to functionally annotate the selected DEGs. Protein-protein interaction (PPI) network of the selected DEGs was visualized by Cytoscape. Lastly, Kaplan-Meier (KM) plotter and Profiling Interactive Analysis (GEPIA) were employed to validate the values of the DEGs. RESULTS: A total of 46 up-regulated and 65 down-regulated DEGs were identified. Of these, up-regulated DEGs were enriched in pathways related to cancer, p53 signaling pathway, ECM-receptor interaction, PI3K-Akt signaling pathway, while down-regulated DEGs were enriched in pathways involved in PPAR signaling pathway, proteoglycans in cancer, focal adhesion. 24 genes were selected from the PPI network analysis by Molecular Complex Detection (MCODE), and 20 vital genes were found to be correlated to poorer overall survival (OS) rates in BC. The prognostic values of these genes were validated by both KM and GEPIA. Finally, the CCNE2, CCNB1 and RRM2 genes were found to be markedly enriched in the p53 signaling pathway through the DAVID analysis. CONCLUSION: This study revealed that the p53 signaling pathway could be an important pathway in BC progression. The three p53-related genes CCNE2, CCNB1 and RRM2 may represent candidate therapeutic gene targets for the treatment of BC.