RESUMEN
OBJECTIVE: This study aimed to investigate the prognostic value of CIP2A (cancerous inhibitor of protein phosphatase 2A) and the NLR (neutrophil-lymphocyte ratio) in the serum of patients with CRC (colorectal cancer) after resection. METHODS: The clinicopathological data of 61 patients who underwent resection between January 2012 and December 2013 were collected. The NLR and CIP2A were divided into low score groups (0) and high score groups (1) with 2.03 and 6.07 as the optimal cut-off value according to the receiver operating characteristic (ROC) curve analysis. To identify the COCN (combination of CIP2A and the NLR) score, we added CIP2A and NLR points together and categorized CRC patients into three groups. Kaplan-Meier curves were used to identify the overall survival (OS) rates of the different groups. Finally, a ROC curve was plotted to evaluate the prognostic efficacy of COCN. RESULTS: The CIP2A was associated with location (P = 0.046) and CEA (P = 0.037) in patients with CRC. Kaplan-Meier survival curves showed that the 5-year OS of patients with low level of serum CIP2A was better than that of high level. The 5-year OS of the patients in the low NLR group was better than that of those in the high NLR group. The COCN score was associated with CEA (P < 0.001) and CA19-9 (P = 0.001). The 5-year OS of the patients in the COCN 0 group was highest, followed by that of those in the COCN 1 and COCN 2 groups. Age, N stage and M stage were factors associated with 5-year OS according to the univariate and multivariate analyses (P < 0.05). The area under the curve (AUC) for COCN was largest, indicating that COCN has better prognostic power than CIP2A or the NLR alone. CONCLUSION: COCN could be used as a better prognostic biomarker for CRC than the NLR or CIP2A alone.
Asunto(s)
Neoplasias Colorrectales , Linfocitos , Neoplasias Colorrectales/diagnóstico , Humanos , Estimación de Kaplan-Meier , Neutrófilos , Pronóstico , Estudios RetrospectivosRESUMEN
Arginine methylation is an important posttranslational modification catalyzed by protein arginine methyltransferases (PRMTs). However, the role of PRMTs in colorectal cancer (CRC) progression is not well understood. Here we report that non-POU domain-containing octamer-binding protein (NONO) is overexpressed in CRC tissue and is a potential marker for poor prognosis in CRC patients. NONO silencing resulted in decreased proliferation, migration, and invasion of CRC cells, whereas overexpression had the opposite effect. In a xenograft model, tumors derived from NONO-deficient CRC cells were smaller than those derived from wild-type (WT) cells, and PRMT1 inhibition blocked CRC xenograft progression. A mass spectrometry analysis indicated that NONO is a substrate of PRMT1. R251 of NONO was asymmetrically dimethylated by PRMT1 in vitro and in vivo. Compared to NONO WT cells, NONO R251K mutant-expressing CRC cells showed reduced proliferation, migration, and invasion, and PRMT1 knockdown or pharmacological inhibition abrogated the malignant phenotype associated with NONO asymmetric dimethylation in both KRAS WT and mutant CRC cells. Compared to adjacent normal tissue, PRMT1 was highly expressed in the CRC zone in clinical specimens, which was correlated with poor overall survival in patients with locally advanced CRC. These results demonstrate that PRMT1-mediated methylation of NONO at R251 promotes CRC growth and metastasis, and suggest that PRMT1 inhibition may be an effective therapeutic strategy for CRC treatment regardless of KRAS mutation status.
Asunto(s)
Neoplasias Colorrectales/genética , Proteínas de Unión al ADN/genética , Proteína-Arginina N-Metiltransferasas/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas de Unión al ARN/genética , Proteínas Represoras/genética , Animales , Arginina , Carcinogénesis/genética , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica , Xenoinjertos , Humanos , Metilación , RatonesRESUMEN
Tissue-derived RNA, DNA and protein samples become more and more crucial for molecular detection in clinical research, personalized and targeted cancer therapy. This study evaluated how to biobanking colorectal tissues through examining the influences of cold ischemic time and freeze-thaw cycles on RNA, DNA and protein integrity. Here, 144 pairs of tumor and normal colorectal tissues were used to investigate the impact of cold ischemic times (0-48h) on RNA, DNA and protein integrity at on ice or room temperature conditions. Additionally, 45 pairs of tissues experienced 0-9 freeze-thaw cycles, and then the RNA, DNA and protein quality were analyzed. On ice, RNA, DNA and protein from colorectal tumor and normal tissues were all stable up to 48h after surgery. At room temperature, RNA in colorectal tumor and normal tissues began to degrade at 8h and 24h, respectively. Meanwhile, the tumor tissues DNA degradation occurred at 24h after surgery at room temperature. Similarly, the protein expression level of tumor and normal tissues began to change at 24h after the surgery at room temperature. Interestingly, tissue RNA and DNA remained stable even after 9 freeze-thaw cycles, whereas the proteins levels were remarkably changed after 7 freeze-thaw cycles. This study provided a useful evidence on how to store human colorectal tissues for biobanking. Preserving the surgical colorectal tissue on ice was an effective way to prevent RNA, DNA and protein degradation. Importantly, more than 7 repeated freeze-thaw cycles were not recommended for colorectal tissues.