ABSTRACT
BACKGROUND: Serum carcinoembryonic antigen (CEA) is an important biomarker for diagnosis, prognosis, recurrence, metastasis monitoring, and the evaluation of the effect of chemotherapy in colorectal cancer (CRC). However, few studies have focused on the role of early postoperative CEA in the prognosis of stage II CRC. METHODS: Patients with stage II CRC diagnosed between January 2007 and December 2015 were included. Receiver operating characteristic (ROC) curves were used to obtain the cutoff value of early postoperative CEA, CEA ratio and CEA absolute value. The areas under curves (AUCs) were used to estimate the predictive abilities of the CEA and T stage. The stepwise regression method was used to screen the factors included in the Cox regression analysis. Before and after propensity score (PS) - adjusted Cox regression and sensitivity analysis were used to identify the relationship between early postoperative CEA and prognosis. Meta-analysis was performed to verify the results. Kaplan-Meier survival curves were used to estimate the effects of CEA on prognosis. RESULTS: We included 1081 eligible patients. ROC curves suggested that the cutoff value of early postoperative CEA was 3.66 ng/ml (P <0.001) and the AUC showed early postoperative CEA was the most significant prognostic marker in stage II CRC (P = 0.0189). The Cox regression and sensitivity analysis before and after adjusting for PS both revealed elevated early postoperative CEA was the strongest independent prognostic factor of OS, DFS, and CSS (P < 0.001). Survival analysis revealed that patients with elevated early postoperative CEA had lower OS (53.62% VS 84.16%), DFS (50.03% VS 86.75%), and CSS (61.77% VS 90.30%) than patients with normal early postoperative CEA (P < 0.001). When the postoperative CEA was positive, the preoperative CEA level showed no significant effect on the patient's prognosis (all P-values were > 0.05). Patients with a CEA ratio ≤0.55 or CEA absolute value ≤-0.98 had a worse prognosis (all P-values were < 0.001). Survival analysis suggested that adjuvant chemotherapy for stage II CRC patients with elevated early postoperative CEA may improve the CSS (P = 0.040). CONCLUSIONS: Early postoperative CEA was a better biomarker for prognosis of stage II CRC patients than T stage and preoperative CEA, and has the potential to become a high-risk factor to guide the prognosis and treatment of stage II CRC patients.
ABSTRACT
Accumulating evidence suggested the participation of long noncoding RNAs (lncRNAs) in regulating various biological processes so as to affecting cancer progression. However, the functional role of most lncRNAs in colorectal carcer (CRC) is still largely covered. In the present study, we disclosed SNHG14 as a carcinogene in CRC development, as it was low-expressed in normal colon tissues but markedly upregulated in CRC cell lines. Besides, SNHG14 contributed to CRC cell proliferation, motility and EMT in vitro, and inhibition of it confined CRC tumor growth and liver metastasis in vivo. Next, the mechanistic investigations confirmed that SNHG14-promoted CRC progression was mediated by EPHA7, which was negatively regulated by SNHG14 in CRC via an EZH2-dependent way. Importantly, EZH2 was proved as a transcription factor of EPHA7 and functioned as a repressor in EPHA7 transcription by enhancing methylation on EPHA7 promoter. Meanwhile, SNHG14 increased EZH2 expression in CRC via stabilizing its mRNA by interacting with FUS, and via freeing its mRNA from miR-186-5p-induced silence. All in all, our observations demonstrated that SNHG14 serves as a facilitator in CRC through targeting EZH2-repressed EPHA7 by enhancing EZH2 via recruiting FUS and absorbing miR-186-5p, indicating a promising new road for CRC diagnosis and treatment.
Subject(s)
Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Enhancer of Zeste Homolog 2 Protein/metabolism , Gene Expression Regulation, Neoplastic , RNA, Long Noncoding/metabolism , Receptor, EphA7/metabolism , Animals , Base Sequence , Cell Line, Tumor , Cell Proliferation/genetics , Disease Progression , Enhancer of Zeste Homolog 2 Protein/genetics , Epigenesis, Genetic , Gene Silencing , Humans , Mice, Inbred BALB C , Mice, Nude , Models, Biological , Mutation/genetics , Neoplasm Metastasis , Phenotype , Protein Binding , RNA, Long Noncoding/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA-Binding Protein FUS/metabolism , Transcription, Genetic , Tumor Burden , Up-Regulation/geneticsABSTRACT
Objective Inhibitor of growth 1 ( ING1 ) gene has been identified as a novel candidate of tumor suppressor gene .Over-expression of ING1 plays well-established roles in numerous cell processes ,inclu-ding DNA repair and cell apoptosis .Our study is to investigate the clinical significances of expression of ING 1 in colorectal cancer ( CRC) .Methods The mRNA level of ING1 in 82 matched samples comprising primary CRC and paired non-cancerous mucosa were detected and compared by quantitative RT -PCR.Then the correlations of mRNA level of ING1 with the clinicopathological characteristics and prognosis of patients with CRC were ana -lyzed.Results (1)In the same matched tissues,the expression level of ING1 was significantly higher in normal tissues than that in cancer tissues.(2)mRNA expression of ING1 was associated with certain clinical -pathologic variables such as tumor infiltrating level ,lymphatic metastasis,distant metastasis and advancing TNM stage .(3) We obtained the expression levels ratio of cancer tissue and normal tissue and found the lower ratio has a lower Disease-Free Survival(DFS)(P<0.0001).(4)ING1,as a candidate of tumor suppressor gene ,remained a sta-tistically-significant prognostic marker in the Cox regression analysis .Conclusion Down-regulation of ING1 may be correlated tightly with the occurrence and progression of sporadic colorectal cancer .Its expression level can be used to predict prognosis of CRC .
