Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is associated with insulin resistance, lipid metabolism, and tumorigenesis. However, the association between the IGF2BP2 polymorphism and oral cancer risk remains unclear. We recruited 1349 male patients with oral cancer and 1198 cancer-free controls. Three single nucleotide polymorphisms IGF2BP2 rs11705701, rs4402960, and rs1470579 were assessed using real-time polymerase chain reaction. The results indicate that the male patients with oral cancer and with the rs11705701 GA+AA, rs4402960 GT+TT, and rs1470579 AC+CC genotypes had increased risk of advanced clinical stage, larger tumor, and progression of lymph node metastasis compared with those with wild-type IGF2BP2. Moreover, according to The Cancer Genome Atlas dataset, high expression of the IGF2BP2 gene is associated with poor survival in patients with head and neck squamous cell carcinoma. In conclusion, our results suggest that IGF2BP2 polymorphisms are associated with less favorable oral cancer clinical characteristics.
The long noncoding RNA, Growth arrest-specific 5 (GAS5) plays a crucial role in the development of oral cancer. However, potential genetic variants in GAS5 that affect the susceptibility and progression of oral cancer have rarely been explored. In this study, two loci of GAS5 single nucleotide polymorphisms (SNPs) (rs145204276 and rs55829688) were genotyped by using the TaqMan allelic discrimination in 1125 oral cancer patients and 1195 non-oral-cancer individuals. After statistical analyses, the distribution of both the GAS5 SNP rs145204276 and GAS5 SNP rs55829688 frequencies were similar between the study and control groups. However, the patients with GAS5 SNP rs145204276 variants (Ins/Del or Del/Del) showed a higher tendency of moderate to poor cell differentiation of oral cancer (OR: 1.454, 95% CI: 1.041–2.031, p = 0.028). Moreover, the GAS5 SNP rs145204276 variants (Ins/Del or Del/Del) in the non-alcohol-drinking population were associated with significantly advanced tumor stage (OR: 1.500, 95% CI: 1.081–2.081, p = 0.015) and larger tumor size (OR: 1.494, 95% CI: 1.076–2.074, p = 0.016). Furthermore, individuals with the GAS5 SNP rs145204276 variant were associated with a higher expression of GAS5 in the GTEx database (p = 0.002), and the higher GAS5 level was associated with poor cell differentiation, advanced tumor stage and larger tumor size in head and neck squamous cell carcinoma from the TCGA database (all p < 0.05). In conclusion, the GAS5 SNP rs145204276 variant is related to poor-differentiation cell status in oral cancer. Besides, the presence of the GAS5 SNP rs145204276 variant is associated with a worse tumor stage and tumor size in oral cancer patients without alcohol drinking.
3 March 2016 in Asia-Pacific Journal of Clinical Oncology
Oral squamous cell carcinoma (OSCC) is particularly prevalent in Taiwan. The goal of this study was to determine the clinicopathological role of insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) proteins as an indicator of clinical outcomes in OSCC patients. In this study, immunohistochemical (IHC) analysis was used to examine IGF2BP2 protein expression in 244 OSCC patients. We investigated the relationships among IGF2BP2 expression, clinicopathological variables, and patient survival. Our results showed that IGF2BP2 cytoplasmic protein expression was significantly correlated with lymph node metastasis, cancer stage, and patient survival. Kaplan-Meier survival curves revealed that elevated cytoplasmic IGF2BP2 expression levels in OSCC patients were associated with poor overall survival. Moreover, multivariate cox proportional hazard models revealed that cytoplasmic IGF2BP2 expression, T status, and lymph node metastasis were independent prognostic factors for survival. In conclusion, IGF2BP2 protein was found to be a helpful predictive marker for OSCC patients, as well as a possible therapeutic target for OSCC treatment.
Visible para-aortic lymph nodes of ≥2 mm in size are common metastatic patterns of colorectal cancer (CRC) seen on imaging. Their prognostic value, however, remains inconclusive. We aimed to assess the prognostic role of visible para-aortic lymph nodes (PALNs). Patients with confirmed pathologic diagnosis of CRC were enrolled. Correlations among clinicopathologic variables were analyzed using the χ2 test. The Cox proportional hazards model was applied for univariate and multivariate analyses. Survival was estimated using the Kaplan-Meier method and log-rank test. A prognostic model for visible PALNs in CRC patients was established. In total, 4527 newly diagnosed CRC patients were enrolled. Patients with visible PALNs had inferior overall survival compared to those without visible PALNs (5-year overall survival, 67% vs. 76%, P = 0.015). Lymphovascular invasion (LVI) (hazard ratio = 1.865, P = 0.015); nodal disease (pN+) status (hazard ratio = 2.099, P = 0.006); elevated preoperative serum carcinoembryonic antigen (CEA) levels (hazard ratio = 2.263, P < 0.001); and visible PALNs ≥10 mm (hazard ratio = 1.638, P = 0.031) were independent prognostic factors for patients with visible PALNs. If each prognostic factor scored one point, 5-year overall survival of lower- (prognostic score 0–1), intermediate- (prognostic score 2), and high- (prognostic score 3–4) risk groups were, 78%. 54%, and 25% respectively (P < 0.001). The prognostic model, which included LVI, pN+ status, preoperative serum CEA level, and the size of visible PALNs, could effectively distinguish the outcome of patients with visible PALNs.