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Background: Microsatellite instability-high (MSI-H) is a form of genomic instability present in 15% of colorectal cancer (CRC) cases. Several differential gene analyses have been conducted on CRC; however, none have specifically explored the differentially expressed genes in MSI-H CRC. Research on the different gene expressions between MSI-H CRC and microsatellite stable (MSS) CRC, and their different patterns of metastasis will provide invaluable insights for diagnosis, prognosis, and treatment. Methods: In this study, the differential expression of 46,602 genes were analyzed across 613 different tissue samples from The Cancer Genome Atlas (TCGA)-colon adenocarcinoma (COAD) and TCGA-rectum adenocarcinoma (READ) as part of a gene association analysis. R package TCGAbiolinks (version 2.18.0) was used to download the data set, and DESeq2 (version 1.30.1) was used for the differential gene analysis. The resulting genes were then analyzed for shared pathways with R package clusterProfiler (version 3.0.4). Results: A total of 237 significantly differentially expressed genes (Padj<0.05) were found between MSI-H and MSS CRC. Differentially expressed genes include insulin like growth factor 2 (IGF2) and fibroblast growth factor 3 (FGF3), and the enriched pathways mostly involve hearing, digestive regulation, and neurogenesis.463 differentially expressed genes were found between metastatic and non-metastatic CRC. Notably differentially expressed genes in metastatic CRC include DEAD-box helicase 53 (DDX53) and adiponectin, C1Q and collagen domain containing (ADIPOQ), and enriched pathways include the immune system, cell adhesion, and cell signaling. For MSI-H CRC, a total of 34 genes were significantly differently expressed between metastatic and non-metastatic CRC. These include notum, palmitoleoyl-protein carboxylesterase (NOTUM), serpin family B member 2 (SERPINB2), and several keratin (KRT) genes, and the pathway analysis showed the major enrichment of the hormonal and secretion and regulation pathways. Of the differentially expressed genes in metastatic CRC, 25 were immunity related and include fatty acid binding protein 4 (FABP4), and the pathway analysis showed the enrichment of humoral immunity and lymphocyte regulation. Conclusions: Of the biologically plausible differentially expressed genes, the most notable were NOTUM, KRT6A, KRT14, SERPINB2, and serum amyloid A1 (SAA1). NOTUM, KRT6A, and KRT14 are active in the Wnt pathway. All five are also involved in various inflammation pathways.
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BACKGROUND: Little is known regarding the survival and functional recovery of elderly intertrochanteric hip fracture (IHF) patients after total hip arthroplasty (THA) versus percutaneous external fixation (PEF). This study aims to analyze the prognostic factors of THA and PEF in elderly IHF patients. METHODS: A total of 155 consecutive elderly patients (mean age of 80 years) diagnosed with IHF were retrospectively reviewed from our database between January 1, 2010, and December 31, 2018. The preoperative, intraoperative and postoperative covariates were analyzed by two independent surgical cohorts: THA and PEF. The main outcomes included the hip function score, all-cause mortality within 1 year after surgery, and overall survival. Covariables and their influence on independent outcomes were analyzed using multivariate regression models. RESULTS: The median follow-up period was 5.1 years, and 6 patients were lost to follow-up. At the endpoint, 70 of 85 patients treated with THA and 37 of 70 patients treated with PEF survived, exhibiting mean Harris hip scores of 84.4 and 69.0, respectively. The Kaplan-Meier curves and log-rank tests showed no significant difference in overall survival. After adjusting for the covariates, the surgical mode was a unique prognostic factor affecting hip function recovery, and two prognostic factors (leukocyte count and D-dimer) were correlated with 1-year all-cause mortality. Age at admission, fracture classification, D-dimer level and surgical mode were identified as prognostic factors affecting overall survival. After adjusting for the former three covariates, THA reduced the risk of death by 67.20% compared with PEF (HR 0.328, 95% CI, 0.121-0.890). CONCLUSIONS: Despite the nonsignificant difference in 1-year all-cause mortality, THA demonstrated superior midterm survival and hip function recovery in elderly IHF patients compared with PEF. Predictive factors, including age at admission, fracture classification, D-dimer level and surgical mode, are associated with the overall survival of IHF in high-risk elderly patients.
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OBJECTIVES: Colorectal cancer is one of the most common malignancies. Recent studies investigated that B7-H4 is highly expressed in various cancers. We aimed at exploring the effect of B7-H4 siRNA on proliferation, invasion, and migration of LOVO cells which expressed B7-H4 notably. DESIGN AND METHODS: Colon adenocarcinoma dataset was downloaded from The Cancer Genome Atlas. 35 colorectal cancer patients admitted to Shanghai Tongren Hospital were enrolled in this study. Cell proliferation and cell cycle distribution were identified by CCK8 and flow cytometry, respectively. Transwell assay was performed to detect the invasion and migration of LOVO cells. CXCL12/CXCR4 expression and JAK2/STAT3 phosphorylation were determined by real-time PCR and western blot. RESULTS: B7-H4 expressed is elevated in colorectal cancer tissues than in the adjacent normal tissues. B7-H4 siRNA effectively inhibited the proliferation at 24 h and 48 h, arrested cell cycle at G0/G1, and suppressed cell invasion and migration. Gene set enrichment analysis showed that CXCL12/CXCR4 and JAK/STAT were correlative with the B7-H4 expression. Additionally, CXCL12/CXCR4 expression and JAK2/STAT3 phosphorylation were reduced. CONCLUSIONS: B7-H4 siRNA can effectively inhibit proliferation, invasion, and migration of LOVO cells by targeting CXCL12/CXCR4 and JAK2/STAT3 signaling, which can serve as a new target for colorectal carcinoma treatment.