Prognostic Significance of Tumor Deposits in Patients With Stage III Colon Cancer: A Nomogram Study.

BACKGROUND: The clinical characteristics of stage III colon cancer and the prognostic significance of tumor deposits were investigated, to construct a prognostic nomogram. METHODS: The data of patients were retrieved from the Surveillance, Epidemiology, and End Results database. Patients were randomized to a training or validation cohort. The Kaplan-Meier method was used to analyze survival rates. In the training cohort, a prognostic nomogram was established via Cox regression and then tested in the validation cohort. The accuracy and discrimination of the nomogram were assessed using concordance indices (C-indices) and calibration curves. RESULTS: Of the 9246 patients meeting the inclusion criteria, 1788 (19.3%) had tumor deposits. Patients with tumor deposits only showed similar survival rates to those with lymph node metastases only (P = 0.83). Compared with these, patients with both tumor deposits and lymph node metastases exhibited significantly worse survival (P < 0.01). In the multivariate Cox regression analyses, the following were identified as independent prognostic indicators and adopted to formulate the nomogram: tumor deposits, age, ethnicity, T stage, the number of positive regional lymph nodes, grade, and carcinoembryonic antigen. In the training cohort, the calibration curve showed good consistency, and the concordance index of the nomogram for predicting overall survival reaches 0.727 (95% CI: 0.71524-0.73876), superior to the concordance index of the American Joint Committee on Cancer staging system (0.594, 95% CI: 0.58224-0.60576). These results are supported in the validation cohort. CONCLUSIONS: Tumor deposits may be an independent prognostic factor for patients with stage III colon cancer after colectomy. The nomogram constructed herein accurately predicted overall survival.

Tropomodulin 3 promotes liver cancer progression by activating the MAPK/ERK signaling pathway.

Tropomodulin 3 (TMOD3) is a member of the pointed­end capping protein family that contributes to invasion and metastasis in several types of malignancies. TMOD3 has been found to be crucial for membranous skeleton and embryonic development; however, little is known regarding the role of TMOD3 in liver cancer progression. In addition, to the best of our knowledge, no previous studies have investigated the mechanism underlying the TMOD3­regulated promotion of liver cancer. The aim of the present study was to determine whether TMOD3 is associated with liver cancer progression. TMOD3 expression was found to be elevated in liver cancer cells and tissues. In the in vitro experiments, liver cancer cell proliferation, invasion and migration were inhibited by TMOD3 knockdown and promoted by ectopic expression of TMOD3. Furthermore, mechanistic analysis indicated that TMOD3 overexpression activated mitogen­activated protein kinase (MAPK)/extracellular signal­regulated kinase (ERK) signaling and increased the levels of other targets of this pathway, including matrix metalloproteinase (MMP)2, MMP9 and cyclin D1. TMOD3 overexpression was associated with changes in liver cancer cell morphology and altered expression of epithelial and mesenchymal markers. High TMOD3 expression was hypothesized to promote epithelial­to­mesenchymal transition in liver cancer cells. In conclusion, TMOD3 was shown to promote liver cancer cell growth, invasion and migration through the MAPK/ERK signaling pathway, and it may serve as a candidate biomarker and therapeutic target in liver cancer.

The clinical significance of CCBE1 expression in human colorectal cancer.

PURPOSE: The identification and discovery of prognostic markers for colorectal cancer (CRC) are of great clinical significance. CCBE1 is expressed in various tumors and its expression correlates with lymphangiogenesis and angiogenesis. However, the association between CCBE1 expression and CRC outcome has not been reported. The aim of this study was to investigate clinical significance of CCBE1 expression in CRC. PATIENTS AND METHODS: CCBE1 expression was examined in 30 pairs of fresh CRC tissues and compared with adjacent normal (AN) tissues using quantitative real-time PCR (qRT-PCR), Western blotting and immunohistochemistry (IHC) staining. Tissue microarray immunohistochemical staining was used to study the CCBE1 expression characteristics of 204 CRC patient samples collected from January 2002 to December 2007, and the relationship of CCBE1 with clinicopathological features and prognosis of CRC was analyzed. RESULTS: CCBE1 was highly expressed in CRC tissues compared with matched AN tissues (P=0.001). Moreover, high expression of CCBE1 was significantly associated with tumor differentiation, lymph node metastasis, vascular invasion, liver metastasis and TNM stage in CRC patients (P≤0.01). Kaplan-Meier survival analysis revealed that high CCBE1 expression, poor tumor differentiation, lymph node metastasis and vascular invasion were significantly associated (all P<0.001) with poor prognosis for patients. Furthermore, univariate and multivariate Cox analysis revealed that high CCBE1 expression, poor tumor differentiation, lymph node metastasis and vascular invasion were independent risk factors for both overall survival (OS) and disease-free survival (DFS) of CRC patients (all P<0.05). OS and DFS of 267 CRC patients from The Cancer Genome Atlas (TCGA) database showed the same trend (log-rank P=6e-04, HR [high] =2.4; log-rank P=0.0081, HR [high] =1.9). CONCLUSION: High levels of CCBE1 contribute to the aggressiveness and poor prognosis of CRC. CCBE1 can serve as a novel potential biomarker to predict CRC patients' prognosis.