Enhanced fatty acid oxidation mediated by CPT1C promotes gastric cancer progression.

BACKGROUND: Carnitine palmitoyltransferase 1C (CPT1C) is a critical enzyme that catalyzes carnitinylation of fatty acids for transport into mitochondria for ß-oxidation. No previous studies have been conducted to explore the prognostic and oncogenic role of CPT1C in gastric cancer (GC). METHODS: Public RNA-sequencing data and micro-array data were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases respectively. Survival analysis was performed in TCGA and GSE62254 cohorts. RT-qPCR and Western blot analyses were used to determine genes expression in GC cells. Fatty acid oxidation (FAO) assay kit was used to examine cell FAO rate. The cell proliferation ability and cell cycle were tested by using CCK-8 and cell cycle assay kits. RESULTS: In the both TCGA and GSE62254 cohorts, high expression of CPT1C was significantly associated with poor overall (OS) (P<0.001) and disease free survival (DFS) of GC patients (P<0.001). Silence of CPT1C significantly inhibited cell FAO rate, suppressed cell proliferation and induced cell cycle arrest, while enforced CPT1C expression had the opposite effects. However, etomoxir treatment completely restricted the increase of FAO rate, cell viability and the phase of DNA synthesis caused by enhanced CPT1C expression. Of note, CPT1C expression was transcriptionally activated by hypoxia inducible factor-1α. CONCLUSIONS: High expression of CPT1C induced by hypoxia was closely associated with poor prognosis and can promote proliferation of GC cells.

High expression of MMP19 is associated with poor prognosis in patients with colorectal cancer.

BACKGROUND: Matrix metalloproteinase 19 (MMP19) is a member of zinc-dependent endopeptidases, which have been involved in various physiological and pathological processes. Its expression has been demonstrated in some types of cancers, but the clinical significance of MMP19 in colorectal cancer (CRC) has not been reported. Thus, we aimed to analyze the clinical significance of MMP19 in CRC in present study. METHODS: The expression of MMP19 was first explored in The Cancer Genome Atlas (TCGA) cohort, and then validated in the GSE39582 cohort and our own database. Clinicopathological features and survival rate were also investigated. RESULTS: MMP19 was found to be a predictor for overall survival (OS) in both univariate (hazard ratio [HR]: 1.449, 95% confidence interval [CI]: 1.108-1.893, P = 0.007) and multivariate survival analyses (HR: 1.401, 95% CI: 1.036-1.894, P = 0.028) in the TCGA database. MMP19 was further validated as an independent factor for recurrence free survival in the GSE39582 database by both univariate analysis (HR: 2.061, 95%CI: 1.454-2.921, P < 0.001) and multivariate analysis (HR = 1.470, 95% CI: 1.025-2.215, P = 0.032). In an in-house cohort, MMP19 was significantly upregulated in CRC tissues when compared with their adjacent normal controls (P < 0.001). Ectopic MMP19 expression was positively associated with lymph node metastases (P = 0.029), intramural vascular invasion (P = 0.015) and serum carcinoembryonic antigen levels (P = 0.045). High MMP19 expression correlated with a shorter OS (HR = 5.595; 95% CI: 2.573-12.164; P < 0.001) and disease free survival (HR = 4.699; 95% CI: 2.461-8.974; P < 0.001) in multivariate cox regression analysis. CONCLUSIONS: Expression of MMP19 was upregulated in CRC. High expression of MMP19 was determined to be an independent and poor prognostic factor in CRC. These results suggest that MMP19 may be a good biomarker for CRC.

[Prognostic value of lymph node ratio in survival of patients with stage III rectal cancer].

OBJECTIVE: To assess the prognostic value of lymph node ratio (LNR) in patients with stage III rectal cancer after curative resection. METHODS: A retrospective review of the clinicopathological data was performed in 161 patients with stage III rectal cancer who received curative surgical excision in our hospital from June 2005 to June 2010. The variables including LNR, age, gender, T stage, N stage, total number of dissected lymph nodes, number of metastatic lymph nodes, and positive rate of lymph node metastasis were studied through univariate and multivariate analyses, and the survival analysis was performed using Kaplan-Meier method and Log rank test. RESULTS: Multivariate analysis revealed that LNR, but not number of positive nodes or number of harvested lymph nodes, had independent prognostic value for overall survival and disease-free survival for patients with stage III rectal cancer. The overall survival in the LNR < 0.43 and LNR ≥ 0.43 groups was 75.8% and 41.3%, respectively (P < 0.01), while the disease-free survival was 68.8% and 40.3%, respectively (P = 0.001). CONCLUSIONS: The LNR is an independent prognostic factor for survival of patients with stage III rectal cancer, and is more efficient than the number of positive nodes and total number of dissected lymph nodes in the survival prediction.