Construction of a clinical survival prognostic model for middle-aged and elderly patients with stage III rectal adenocarcinoma.

BACKGROUND: Nomograms for prognosis prediction in colorectal cancer patients are few, and prognostic indicators differ with age. AIM: To construct a new nomogram survival prediction tool for middle-aged and elderly patients with stage III rectal adenocarcinoma. METHODS: A total of 2773 eligible patients were divided into the training cohort (70%) and the validation cohort (30%). Optimal cutoff values were calculated using the X-tile software for continuous variables. Univariate and multivariate Cox proportional hazards regression analyses were used to determine overall survival (OS) and cancer-specific survival (CSS)-related prognostic factors. Two nomograms were successfully constructed. The discriminant and predictive ability and clinical usefulness of the model were also assessed by multiple methods of analysis. RESULTS: The 95%CI in the training group was 0.719 (0.690-0.749) and 0.733 (0.702-0.74), while that in the validation group was 0.739 (0.696-0.782) and 0.750 (0.701-0.800) for the OS and CSS nomogram prediction models, respectively. In the validation group, the AUC of the three-year survival rate was 0.762 and 0.770, while the AUC of the five-year survival rate was 0.722 and 0.744 for the OS and CSS nomograms, respectively. The nomogram distinguishes all-cause mortality from cancer-specific mortality in patients with different risk grades. The time-dependent AUC and decision curve analysis showed that the nomogram had good clinical predictive ability and decision efficacy and was significantly better than the tumor-node-metastases staging system. CONCLUSION: The survival prediction model constructed in this study is helpful in evaluating the prognosis of patients and can aid physicians in clinical diagnosis and treatment.

Polymorphisms in human telomerase reverse transcriptase (hTERT) gene, gene- gene and gene-smoking interaction with susceptibility to gastric cancer in Chinese Han population.

AIMS: To investigate the association of telomerase reverse transcriptase (TERT) gene polymorphisms and additional gene-gene and gene- environment interaction with gastric cancer (GC) risk. RESULTS: GC risk was significantly higher in carriers of G allele of rs2736100 than those with TT genotype (TG+ GG versus TT), adjusted OR (95%CI) =1.68 (1.26-2.17), and higher in carriers of G allele of rs2853669 than those with AA genotype (AG+ GG versus AA), adjusted OR (95%CI) = 1.72 (1.19-2.33). We also found that interaction between rs2736100 and smoking was associated with higher GC risk. Smokers with TG or GG of rs2736100 genotype have elevated GC risk, compared to never- smokers with TT of rs2736100 genotype, OR (95%CI) = 3.12 (1.82 -4.61). Pairwise linkage equilibrium (LD) analysis between SNPs was measured and the D' value between rs2736100 and rs2736109 was more than 0.8. A haplotype containing the rs2736100- G and rs2736109- A alleles was associated with a statistically increased GC risk (OR= 2.66, 95%CI= 1.28 - 4.12, p<0.0001). MATERIALS AND METHODS: A total of 1088 participants (686 males, 402 females) were selected, including 360 GC patients and 728 normal participants. Logistic regression was performed to investigate association between single nucleotide polymorphisms (SNPs) within TERT gene and GC susceptibility. Generalized multifactor dimensionality reduction (GMDR) model was used to screen gene- gene and gene- environment interaction combinations. CONCLUSIONS: We found that G allele of rs2736100 and G allele of rs2853669 in TERT gene, interaction between rs2736100 and smoking, and haplotype containing the rs2736100- G and rs2736109- A alleles were all associated with increased GC risk.

[Prognosis analysis of 247 cases of gastrointestinal stromal tumor].

OBJECTIVE: To study the clinicopathologic features and prognostic factors of gastrointestinal stromal tumor (GIST). METHODS: Clinicopathologic data of 247 patients with GIST from January 2003 to November 2012 in the Affiliated Hospital of Qingdao University Medical College, and the prognostic factors were evaluated retrospectively by univariate and multivariate analysis with Log-rank test and Cox proportional hazard model. RESULTS: Patients were followed up with a median time of 26 months (1 to 113 months). Twenty-six patients developed recurrence or metastasis, and 18 died of GIST. The 1-, 3-, 5-year survival rates were 94%, 91% and 83% respectively. Univariate analysis showed that age, tumor location, tumor size, mitotic count and tumor rupture were predictive factors of survival after resection of primary GIST (all P<0.01). For patients at intermediate and high risk to relapse, imatinib group had a higher 5-year overall survival rate than non-imatinib group (85.7% vs. 81.0%, P<0.05). Multivariate analysis revealed that tumor size (RR=2.248, 95%CI:1.081-4.677, P=0.030), mitotic count (RR=2.220, 95%CI:1.032-4.776, P=0.041) and tumor rupture (RR=5.183, 95%CI:1.677-16.017, P=0.004) were independent prognostic factors. CONCLUSIONS: Tumor size, mitotic count and tumor rupture affect the prognosis after resection of primary GIST independently. Imatinib adjuvant therapy can improve overall survival of patients at intermediate and high risk to relapse after surgery.

S100A4 silencing blocks invasive ability of esophageal squamous cell carcinoma cells.

AIM: To investigate a potential role of S100A4 in esophagus squamous cell carcinoma metastasis (ESCCs). METHODS: Expression of S100A4 and E-cadherin were analyzed in frozen sections from ESCCs (metastasis, n = 28; non-metastasis, n = 20) by reverse transcription-polymerase chain reaction, quantitative polymerase chain reaction and immunohistochemistry. To explore the influence of S100A4 on esophageal cancer invasion and metastasis, S100A4 was overexpressed or silenced by S100A4 siRNA in TE-13 or Eca-109 cells in vitro and in vivo. RESULTS: We found the mRNA and protein levels of S100A4 expression in ESCCs was significantly upregulated, and more importantly, that expression of S100A4 and E cadherin are strongly negatively correlated in patients who had metastasis. It was indicated that overexpression of S100A4 in TE-13 and Eca-109 cells downregulates the expression of E-cadherin, leading to increased cell migration in vitro, whereas knockdown of S100A4 inhibited cell migration and upregulation of E-cadherin expression. Moreover, the loss of cell metastatic potential was rescued by overexpression of E-cadherin completely. In addition, nude mice inoculated with S100A4 siRNA-transfected cells exhibited a significantly decreased invasion ability in vivo. CONCLUSION: S100A4 may be involved in ESCC progression by regulate E-cadherin expression, vector-based RNA interference targeting S100A4 is a potential therapeutic method for human ESCC.

The E-cadherin repressor slug and progression of human extrahepatic hilar cholangiocarcinoma.

OBJECTIVES: This study explored the expression and function of Slug in human extrahepatic hilar cholangiocarcinoma (EHC) to identify its role in tumor progression. METHODS: The expression of Snail and Slug mRNA in 52 human tissue samples of EHC was investigated. The mRNA of Snail and Slug were quantified using reverse transcriptase-PCR, and correlations with E-cadherin expression and clinicopathological factors were investigated. We then investigated transfection of Slug cDNA in endogenous E-cadherin-positive human EHC FRH0201 cells, selectively induced the loss of E-cadherin protein expression, and then small interfering RNA (siRNA) for inhibition of Slug expression in endogenous Slug-positive human EHC QBC939 cells, selectively induced the loss of Slug protein expression. A Boyden chamber transwell assay was used for invasion. RESULTS: Slug mRNA was overexpressed in 18 cases (34.6%) of EHC compared with adjacent noncancerous tissue. E-Cadherin protein expression determined in the same 52 cases by immunohistochemistry was significantly down-regulated in those cases with Slug mRNA overexpression (P = 0.0001). The tumor and nontumor ratio of Slug mRNA was correlated with nodal metastasis(p = 0.0102), distant metastasis (p = 0.0001)and Survival time(p = 0.0443). However, Snail mRNA correlated with neither E-cadherin expression nor tumor invasiveness. By inhibiting Slug expression by RNA interference, we found that reduced Slug levels upregulated E-cadherin and decreased invasion in QBC939 cell. When the QBC939 cells was infected with Slug cDNA,, significant E-cadherin was downregulated and increased invasion in QBC939 cell. CONCLUSIONS: The results suggested that Slug expression plays an important role in both the regulation of E-cadherin expression and in the acquisition of invasive potential in human EHC. Slug is possibly a potential target for an antitumor therapy blocking the functions of invasion and metastasis in human EHCs.