Socioeconomic deprivation and survival outcomes in patients with colorectal cancer.

Socioeconomic deprivation has been linked to detrimental healthcare outcomes. We sought to examine whether patients with colorectal cancer (CRC) from socioeconomically disadvantaged areas experience worse survival outcomes and how it interacts with other factors. In this population-based study, patients with CRC diagnosed between 2007 to 2015 in the SEER program were reviewed. Socioeconomic deprivation was measured using the Area Deprivation Index (ADI) linked to patients' residence addresses. The effect of ADI on cancer-specific survival and overall survival was evaluated using survival analysis. The Inverse Probability of Weighted (IPW) method and multiple regression was performed to account for the confounding bias. Subgroup analyses were used to test interactions. Multiple mediation analysis was used to estimate the mediating effects. Overall, 266,620 eligible patients were included in further analyses. Compared with low ADI patients, high ADI patients had more unfavorable characteristics and worse cancer-specific (hazard ratio [HR] 1.14, 95% CI 1.12-1.16, P<.001) and overall survival (HR 1.11, 95% CI 1.09-1.12, P<0.001). The results were similar after accounting for confounding factors using the IPW and multiple regression methods. Subgroup analyses revealed the relative robustness of ADI as a prognostic factor. They detected significant interactions between ADI and other covariates on cancer survival, such as age, race, insurance status, disease stage, and receipt of treatment. Multiple mediation analyses identified several factors mediating survival disparities, including anticancer therapy, insurance status, race, marital status, and age. This study suggested that high ADI CRC patients were associated with more unfavorable characteristics at presentation and lower cancer and noncancer survival after treatment than their low ADI counterparts. Multiple factors interacted and mediated these survival disparities associated with the ADI.

The Prognostic Value of Long Non-Coding RNA SNHG7 in Human Cancer: A Meta-Analysis.

BACKGROUND: The long non-coding RNA SNHG7 is upregulated in many types of cancer and plays a role as an oncogene. However, its overall predictive ability in human cancer prognosis has not been assessed using existing databases. Therefore, further study of its prognostic value and clinical significance in human malignancies is warranted. METHODS: We systematically collected relevant literature from multiple electronic document databases about the relationship between SNHG7 expression level and prognosis in patients with solid cancers. We further screenped them for eligibility. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to assess the prognostic value. Odds ratios (ORs) and their 95% CIs were collected to evaluate the relationship between the expression of SNHG7 and clinicopathological features, including lymph node metastasis (LNM), tumour size, tumour node metastasis (TNM) stage and histological grade. RESULTS: Fourteen original studies involving 971 patients were enrolled strictly following the inclusion and exclusion criteria. The meta-analysis showed that SNHG7 expression significantly correlated with poor overall survival (HR = 1.93, 95% CI: 1.64-2.26, p<0.001) in human cancer patients. In addition, the pooled OR indicated that overexpression of SNHG7 was associated with earlier LNM (OR = 1.83, 95% CI: 1.44-2.32; P <0.001), and advanced TNM stage (OR = 1.82, 95% CI: 1.44-2.30; P <0.001). Meanwhile, there was no significant heterogeneity between the selected studies, proving the reliability of the meta-analysis results. CONCLUSION: High SNHG7 expression may predict poor oncological outcomes in patients with multiple human cancers, which could be a novel prognostic biomarker of unfulfilled clinicopathological features. However, further high-quality studies are needed to verify and strengthen the clinical value of SNHG7 in different types of cancer.

Nuclear IGF1R interacts with NuMA and regulates 53BP1­dependent DNA double­strand break repair in colorectal cancer.

Nuclear insulin­like growth factor 1 receptor (nIGF1R) has been associated with poor overall survival and chemotherapy resistance in various types of cancer; however, the underlying mechanism remains unclear. In the present study, immunoprecipitation­coupled mass spectrometry was performed in an IGF1R­overexpressing SW480­OE colorectal cancer cell line to identify the nIGF1R interactome. Network analysis revealed 197 proteins of interest which were involved in several biological pathways, including RNA processing, DNA double­strand break (DSB) repair and SUMOylation pathways. Nuclear mitotic apparatus protein (NuMA) was identified as one of nIGF1R's colocalizing partners. Proximity ligation assay (PLA) revealed different levels of p53­binding protein 1 (53BP1)­NuMA colocalization between IGF1R­positive (R+) and IGF1R­negative (R­) mouse embryonic fibroblasts following exposure to ionizing radiation (IR). 53BP1 was retained by NuMA in the R­ cells during IR­induced DNA damage. By contrast, the level of NuMA­53BP1 was markedly lower in R+ cells compared with R­ cells. The present data suggested a regulatory role of nIGF1R in 53BP1­dependent DSB repair through its interaction with NuMA. Bright­field PLA analysis on a paraffin­embedded tissue microarray from patients with colorectal cancer revealed a significant association between increased nuclear colocalizing signals of NuMA­53BP1 and a shorter overall survival. These results indicate that nIGF1R plays a role in facilitating 53BP1­dependent DDR by regulating the NuMA­53BP1 interaction, which in turn might affect the clinical outcome of patients with colorectal cancer.

EphA2-YES1-ANXA2 pathway promotes gastric cancer progression and metastasis.

Erythropoietin-producing hepatocellular receptor A2 (EphA2) is a key member of the receptor tyrosine kinase (RTK) family, while YES Proto-Oncogene 1 (YES1) is a non-receptor tyrosine kinase (nRTK) and annexin A2 (ANXA2) belongs to the calcium-dependent phospholipid-binding protein family annexins. Here, we show that EphA2, YES1, and ANXA2 form a signal axis, in which YES1 activated by EphA2 phosphorylates ANXA2 at Tyr24 site, leading to ANXA2 activation and increased ANXA2 nuclear distribution in gastric cancer (GC) cells. Overexpression (OE) of YES1 increases, while knockdown (KD) of YES1 or ANXA2 decreases GC cell invasion and migration in vitro and tumor growth in mouse models. Reexpression of wildtype (WT) rather than mutant ANXA2 (Tyr24F) in ANXA2 knockdown (ANXA2-KD) GC cells restores YES1-induced cell invasion and migration, while neither WT nor mutant ANXA2 (Tyr24F) can restore cell invasion and migration in YES1-KD GC cells. In addition, the activation of EphA2-YES1-ANXA2 pathway is correlated with poor prognosis. Thus, our results establish EphA2-YES1-ANXA2 axis as a novel pathway that drives GC invasion and metastasis, targeting this pathway would be an efficient way for the treatment of GC.

The FENDRR/miR-214-3P/TET2 axis affects cell malignant activity via RASSF1A methylation in gastric cancer.

To explore the effect of fetal-lethal non-coding developmental regulatory RNA (FENDRR) in the initiation and progression of gastric cancer (GC). We detected the levels of FENDRR, microRNA-214-3p (miR-214-3p), and ten-eleven-translocation (TET2) in GC tissues and GC cell lines. In addition, we evaluated the location of FENDRR in GC cell lines by fluorescence in situ hybridization (FISH). Cell proliferation and apoptosis were measured by CCK-8 and Hoechst staining assays. Methylation-specific PCR assay (MSP) was used to evaluate the methylation status of ras-association domain family 1A (RASSF1A). We also observed the direct binding of miR-214-3p on FENDRR by dual-luciferase activity assay in GC cells. FENDRR and TET2 expressions were significantly down-regulated and miR-214-3p was up-regulated in gastric cancer tissues compared to adjacent unaffected tissues. In addition, RASSF1A was hypermethylated in gastric cancer tissues compared to adjacent tissues. The expressions of all the three indicators were influenced by differentiation of tumor, TNM stage of tumors, and lymph node metastasis in patients with GC. A gastric cancer cell line with low FENDRR expression compared to a high FENDRR expressing cell line showed again increased miR-214-3p expression, decreased TET2 and RASSF1A expressions, and RASSF1A hypermethylation, resulting in decreased apoptosis and increased proliferation. Furthermore, we observed a negative correlation between FENDRR and miR-214-3p in GC. The FENDRR/miR-214-3P/TET2 axis plays a critical role in GC progress via methylation of RASSF1A.

Upregulated Expression of Long Non-Coding RNA, LINC00460, Suppresses Proliferation of Colorectal Cancer.

Through bioinformatics analysis, a novel lncRNA, LINC00460, was implicated in the development of multiple cancers. However, the precise expression pattern, clinical significance and biological function of LINC00460 in colorectal cancer (CRC) remain unknown. Network databases were used to investigate the correlation between LINC00460 and CRC. In situ hybridization was performed to verify the precise expression pattern and clinical significance of LINC00460 in a CRC tissue microarray, which included 92 pairs of CRC and adjacent normal tissues. The effect of LINC00460 on proliferation was evaluated by MTT, colony formation assays and flow cytometry employing SW620 and HCT116 cell lines. Cell migration and matrigel invasion assays were performed to investigate whether LINC00460 is involved in the metastasis of CRC. The expression of LINC00460 was significantly upregulated in CRC tissues and cells, associated with early stage CRC and low disease-free survival. The downregulated of LINC00460 expression increased cell proliferation by regulating the cell cycles of SW620 and HCT116 cells. LINC00460 knockdown did not affect cell migration or invasion in vitro. These findings suggest that LINC00460 may be an interesting target for the development of CRC.

Circulating cell free DNA as the diagnostic marker for colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Quantitative analyses of circulating cell-free DNA (cfDNA) are suggested to be a promising method for the detection of colorectal cancer, validated clinical relevance of cfDNA has not been published so far. Though some of the inconsistent results were published. This study is the first meta-analysis to systematically evaluate the diagnostic accuracy of circulating cfDNA as non-invasive biomarkers for colorectal cancer. RESULTS: Fourteen studies concerning a quantitative analysis of circulating cfDNA for the diagnosis of colorectal cancer met the inclusion criteria. Data includes 1,258 patients with colorectal cancer and 803 healthy individuals as control was analyzed. The summary estimates were as follow: sensitivity, 0.735 (95% CI 0.713-0.757); specificity, 0.918 (95% CI, 0.900-0.934); positive likelihood ratio, 8.295 (95% CI, 5.037-13.659); negative likelihood ratio, 0.300 (95% CI, 0.231-0.391); diagnostic odds ratio, 30.783 (95% CI, 16.965-55.856); and area under the curve, 0.8818 (95% CI, 0.88-0.93), respectively. Publication bias was not evident with Deeks' funnel plot asymmetry test (p = 0.197). MATERIALS AND METHODS: A systematic literature was searched in PubMed, EMBASE, Cochrane Library and Chinese National Knowledge Infrastructure from their inception to August 07, 2017. Analyses were conducted by Meta-DiSc 1.4 and Stata 12.0. Diagnostic accuracy in sensitivity, specificity and aspects were pooled. Subgroup analyses and meta-regression were performed to identify the sources of heterogeneity. Clinical utility of the cfDNA was evaluated by Fagan nomogram. CONCLUSIONS: Our meta-analysis suggested that the diagnostic accuracy of circulating cfDNA has unsatisfactory sensitivity but acceptable specificity for diagnosis of colorectal cancer. Furthermore, the integrity index (ALU247/ALU115) is better than absolute DNA concentration in diagnostic accuracy of colorectal cancer.