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Background: We investigated the differences in biological behaviors of sporadic colorectal cancer (CRC) between young and elderly patients. CRC is a common cancer, with a mean age at onset of > 65 years. However, recent reports indicate increasing rates in younger populations. The biological behaviors of sporadic CRC in elderly patients could differ from those in young patients. Methods: Between September 2007 and August 2012, we selected 723 CRC patients from our institution. The patients were divided into Group Y (n = 127, aged ≤50 years) and Group O (n = 596, aged >50 years). The clinicopathologic and oncologic outcomes in the two groups were compared. Results: Group Y tumors were characterized by higher incidences of mucin production (13.4% vs. 6.7%; P = 0.017), high microsatellite instability (MSI-H) (19.8% vs. 5.2%; P < 0.001), and N2 stage (32.3% vs. 22.1%; P = 0.020) than those in Group O. The recurrence rates were similar in both groups (14.9% vs. 17.3%; P = 0.665). The 5-year overall survival and disease-free survival did not differ. Multivariate analysis indicated that cellular differentiation and pathologic stage were significant prognostic factors for 5-year overall survival. Conclusion: Although age was not a prognostic factor for overall survival and young patients did not show a worse prognosis, there were differences in mucin production, MSI-H, and N2 stage between the two groups. Further studies are needed to clarify the clinical and biological characteristics of CRC, improve its treatment strategies, and promote better outcomes in young patients. [ABSTRACT FROM AUTHOR]

Background It is considered that stage II colorectal cancers have heterogeneous oncological outcomes. It remains to be determined whether inflammatory markers can predict survival after curative surgery in these patients. The aim of this study was to investigate the prognostic impact of preoperative inflammatory markers after curative surgery in stage II colorectal cancers. Methods Two hundred sixty-one patients with stage II colorectal cancers who underwent curative surgery between January 2006 and December 2011 were reviewed. Oncologic outcomes were analyzed with neutrophil count, lymphocyte count, monocyte count, neutrophil to lymphocyte ratio (NLR), and lymphocyte to monocyte ratio. Results Univariate analysis showed that high NLR (hazard ratio (HR), 3.506; 95% confidence interval [CI], 1.415-8.688; P = 0.007) and low LMR (HR, 2.436; 95% CI, 1.010-5.880; P = 0.048) were associated with worse disease-free survival (DFS), and high NLR (HR, 2.834; 95% CI, 1.419-5.662; P = 0.003) and low LMR (HR, 2.374; 95% CI, 1.188-4.742; P = 0.014) were associated with worse overall survival (OS) in stage II colorectal cancer. Cox multivariate analysis demonstrated that high NLR was independently associated with worse DFS (HR, 3.163; 95% CI, 1.058-9.455; P = 0.004) and OS (HR, 3.018; 95% CI, 1.467-6.207; P = 0.003) in stage II colorectal cancer. Conclusion Among the systemic inflammatory markers, NLR is a strong predictor of worse DFS and OS in stage II colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: Discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase that utilizes collagen as a ligand, is a key molecule in the progression of solid tumors as it regulates the interaction of cancer cells with the tumor stroma. However, the clinical relevance of DDR1 expression in gastric carcinoma is yet to be investigated. Here, we assessed the role of DDR1 in mediating the aggressive phenotype of gastric carcinoma and its potential as a therapeutic target.Methods: We conducted DDR1 immunohistochemistry using a tissue microarray of 202 gastric carcinoma specimens. We examined the effect of collagen-induced activation of DDR1 on cell signaling, tumorigenesis, and cell migration in gastric cancer cell lines, and tumor growth in a xenograft animal model of gastric cancer.Results: Our results showed that 50.5% of gastric cancer tissues are positive for DDR1 expression, and positive DDR1 expression was significantly correlated with a poor prognosis (P = 0.015). In a subgroup analysis, DDR1 expression was prognostically meaningful only in patients receiving adjuvant treatment (P = 0.013). We also demonstrated that collagen was able to activate DDR1 and increase the clonogenicity and migration of gastric cancer cells. We observed that a DDR1 inhibitor, 7rh benzamide, suppressed tumor growth in gastric cancer xenografts.Conclusions: Our findings suggest a key role for DDR1 signaling in mediating the aggressive phenotype of gastric carcinoma. Importantly, inhibition of DDR1 is an attractive strategy for gastric carcinoma therapy. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore novel genomic biomarkers predicting hepatocellular carcinoma (HCC) prognosis by integrative analysis of DNA copy number aberrations (CNAs) and gene expression profiles. Array comparative genomic hybridization and expression array were performed on 45 and 31 HCC samples, respectively. To identify functionally important genes, concordant results of DNA copy number and gene expression were retrieved by integrative analysis. Cox regression analysis indicated that the CNAs in 192 genomic regions were significantly associated with overall survival (OS; p < 0.05). Integrative analysis capturing concordant results demonstrated that the low expression of TLE4 ( p = 0.041) and XPA ( p = 0.006) was associated with poor OS. In the analysis of tumor recurrence, 514 genomic regions with CNAs were associated with recurrence. Integrative analysis revealed that the overexpression of 16 genes, including FGR ( p = 0.003), RELA ( p = 0.049), LTBP3 ( p = 0.050), and RIN1 ( p = 0.023), was significantly associated with shorter time to tumor recurrence. On multivariate analysis, FGR and XPA were independent risk factors of early recurrence and poor OS, respectively. Integrated analysis of CNAs and gene expression profiles correlated with long-term follow-up data successfully identified potential prognostic markers predicting survival and tumor recurrence in patients with HCC who underwent surgical resection. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the feasibility of mesorectal vascular invasion (MVI) in predicting early distant metastasis developed within 1 year of diagnosis of T3 rectal cancer using magnetic resonance imaging (MRI) METHODS: Sixty-five patients with T3 rectal cancer (early metastasis, n = 28; non-metastasis, n = 37) were enrolled in this study. Early distant metastases developed in 28 patients (liver, n = 15; lung, n = 9; both, n = 4). Logistic regression was used to determine the independent predictors for early distant metastasis.Results: In univariate analysis, tumour location, carcinoembryonic antigen (CEA), lymphovascular invasion (LVI), MRI-detected MVI, and mesorectal fat infiltration (MFI) (odds ratio [OR], 4.533, 9.583, 5.539, 27.046, and 5.539, respectively) were associated with early distant metastasis. Multivariate analysis demonstrated that MVI (OR, 29.949; P < 0.002) and LVI (OR, 6.684; P = 0.033) were independent factors for early distant metastasis. Specificity and positive predictive value (PPV) of MVI (94.59%, and 89.47%, respectively) were significantly higher than those of LVI (64.86%, and 61.76%), but sensitivity and negative predictive value were not significantly different between MVI (60.71%, and 76.09%) and LVI (75.00%, and 77.42%).Conclusions: While sensitivity of MRI-detected MVI was equal to that of CEA in predicting early distant metastasis from T3 rectal cancer, specificity and PPV may be improved by assessing MVI.Key Points: • Mesorectal vascular invasion (MVI) may be a radiologic prognostic factor for rectal cancer. • Specificity of MVI was higher than lymphovascular invasion in predicting early metastasis. • Mesorectal vascular invasion may be a better predictor for early distant metastasis. [ABSTRACT FROM AUTHOR]