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Tumor size is an independent risk predictor for metachronous colorectal cancer.

ABSTRACT: Non-hereditary colorectal cancer (CRC) patients are at higher risk of developing independent metachronous CRC than cancer-naïve individuals, but the reason is unknown. We studied metachronous CRC risk factors among one thousand five Japanese CRC patients who underwent surgery for CRC. Relative hazard risk of clinical and pathological features was assessed by univariate and multivariate Cox's proportional hazard regression analysis. Observed metachronous CRC incidence was also compared with the expected cancer incidence of the general population in Japan. Twenty-seven metachronous CRCs developed in 24 patients (2.4%) during a follow-up period of 3,676 person-years. Multivariate analysis revealed two factors associated with a high metachronous CRC risk: synchronous CRC (HR = 6.13; p = 1.3x10(-4)) and tumor size ? 6.5 cm (HR = 4.34; p = 1x10(-3)). Patients with either synchronous or large solitary tumors exhibited a higher risk for metachronous CRC than patients with solitary small tumors (HR = 7.3; p = 4.3x10(-6)) and that the general Japanese population (SIR = 7.01; p = 3.5x10(-9)), while patients with solitary small tumors did not (SIR = 1.07; p = 0.8). If patients younger than 60 years were excluded, the observations remained unchanged, with tumor size becoming stronger predictor (HR = 5.67; p = 1.7x10(-4)) than the presence of synchronous CRC (HR = 5.34; p = 9.6x10(-4)). Our novel finding that primary tumor size is a strong independent risk factor for metachronous CRC increases the sensitivity of prediction more than twice the presence of synchronous CRC. Our data provides new insights to assess the risk for metachronous lesions that should improve the surveillance regimen for CRC.

SUBMITTER: Kato T

PROVIDER: S-EPMC4951258 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Tumor size is an independent risk predictor for metachronous colorectal cancer.

Kato Takaharu T Alonso Sergio S Muto Yuta Y Perucho Manuel M Rikiyama Toshiki T

Oncotarget 20160401 14

Non-hereditary colorectal cancer (CRC) patients are at higher risk of developing independent metachronous CRC than cancer-naïve individuals, but the reason is unknown. We studied metachronous CRC risk factors among one thousand five Japanese CRC patients who underwent surgery for CRC. Relative hazard risk of clinical and pathological features was assessed by univariate and multivariate Cox's proportional hazard regression analysis. Observed metachronous CRC incidence was also compared with the e ...[more]

PMID: 26910116

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Project description:BackgroundMetachronous colorectal cancer refers to patients developing a second colorectal neoplasia diagnosed at least 6 months after the initial cancer diagnosis, excluding recurrence. The aim of this systematic review is to assess the incidence of metachronous colorectal cancer in early-onset colorectal cancer (defined as age at diagnosis of less than 50 years) and to identify risk factors.MethodsThis is a systematic review and meta-analysis performed following the PRISMA statement and registered on PROSPERO. The literature search was conducted in PubMed and Embase. Only studies involving patients with early-onset colorectal cancer (less than 50 years old) providing data on metachronous colorectal cancer were included in the analysis. The primary endpoint was the risk of metachronous colorectal cancer in patients with early-onset colorectal cancer. Secondary endpoints were association with Lynch syndrome, family history and microsatellite instability.ResultsSixteen studies met the inclusion criteria. The incidence of metachronous colorectal cancer was 2.6% (95% c.i. 2.287-3.007). The risk of developing metachronous colorectal cancer in early-onset colorectal cancer versus non-early-onset colorectal cancer patients demonstrated an OR of 0.93 (95% c.i. 0.760-1.141). The incidence of metachronous colorectal cancer in patients with Lynch syndrome was 18.43% (95% c.i. 15.396-21.780), and in patients with family history 10.52% (95% c.i. 5.555-17.659). The proportion of metachronous colorectal cancer tumours in the microsatellite instability population was 19.7% (95% c.i. 13.583-27.2422).ConclusionThe risk of metachronous colorectal cancer in patients with early-onset colorectal cancer is comparable to those with advanced age, but it is higher in patients with Lynch syndrome, family history and microsatellite instability. This meta-analysis demonstrates the need to personalize the management of patients with early-onset colorectal cancer according to their risk factors.

Project description:Spindle Apparatus Coiled-Coil Protein 1 (SPDL1) is a relatively recently identified coiled-coil domain containing protein and an important determinant of DNA fidelity by ensuring faithful mitosis. Hence, SPDL1 is suspected to underlie genomic (in-)stability in human cancers, yet its exact roles in these diseases remain largely underexplored. Given that genomic instability (GIN) is a crucial feature in colorectal cancer (CRC), we primarily asked whether the expression of this protein may account for differences in clinicopathological features and survival rates of CRC patients. Protein expression was evaluated by immunohistochemistry in the institutional tissue microarray (TMA), and gene expression by the analysis of publicly available datasets. To place the prognostic relevance in a predicted biological context, gene co-expression set around SPDL1 identified by public data mining was annotated and assessed for enrichment in gene ontology (GO) categories, BRITE hierarchies, and Reactome pathways. The comparison with adjacent normal tissue revealed a high expression of SPDL1 protein in a subset of tumor cases (48.84%), and these had better prognosis than the SPDL1-low expression counterpart even after adjustment for multiple confounders. SPDL1-high expression within tumors was associated with a median 56-month survival advantage, but not with any clinicopathological characteristics of our cohort. In the TCGA cohort, SPDL1 was overexpressed in tumor tissue and positively associated with improved survival, chromosome instability phenotype, and various GIN markers. In addition to the genes critically involved in the cell cycle and mitosis, a gene set co-expressed with SPDL1 contained checkpoint members of both chromosome segregation and DNA replication, as well as those associated with defective DNA repair, and retrograde vesicle-mediated transport. In conclusion, SPDL1 is an independent predictor of CRC patient survival in a possible connection with chromosomal instability.

Project description:This study aimed to explore the mechanisms of bridging integrator-3 dysregulation, its prognostic value, and related signaling pathways in colorectal cancer . Bioinformatic analysis was performed based on the data from The Cancer Genome Atlas–colorectal cancer and Human Protein Atlas. Colorectal cancer cell lines, LoVo and HT29 cells, were used as in vitro cell model to assess the effect of demethylation on bridging integrator-3 expression. Results showed that bridging integrator-3 was downregulated in colorectal cancer tissues compared to normal colon and rectum tissues. Heatmap of bridging integrator-3 messenger RNA expression, exon expression, and DNA methylation indicated a negative correlation between bridging integrator-3 expression and methylation of some CpG sites within the coding sequence. Demethylation treatment significantly increased bridging integrator-3 expression in LoVo and HT29 cells. Low bridging integrator-3 messenger RNA and exon expression were associated with significantly worse overall survival (P = .015 and .013, respectively). Multivariate analysis confirmed that low bridging integrator-3 messenger RNA expression was an independent prognostic factor of unfavorable overall survival (Hazard Ratio (HR) = 1.596, 95% confidence interval: 1.024-2.486; P = .039). High bridging integrator-3 DNA methylation was also associated with significantly worse overall survival (P = .013). Kyoto Encyclopedia of Genes and Genomes analysis indicated that the genes correlated with bridging integrator-3 (absolute Pearson r ≥ 0.3, n = 121) were enriched in sphingolipid signaling pathway, natural killer cell-mediated cytotoxicity, p53 signaling pathway, and apoptosis. Based on these findings, we infer that DNA hypermethylation might be an important mechanism of suppressed bridging integrator-3 expression in colorectal cancer . Its low expression is an independent predictor of unfavorable survival in patients with primary colorectal cancer . Bridging integrator-3 might act as a tumor suppressor via modulating natural killer cell-mediated cytotoxicity, p53 signaling pathway, and apoptosis.

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Tumor size is an independent risk predictor for metachronous colorectal cancer.

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Tumor size is an independent risk predictor for metachronous colorectal cancer.

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