Guangyuan Hu

Pretreatment hematologic markers as prognostic factors in patients with nasopharyngeal carcinoma: Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio

Pretreatment hematological markers of inflammatory response have emerged as prognostic factors for patients with cancer. In this study, we evaluated the prognostic significance of various hematologic parameters in patients with nasopharyngeal carcinoma (NPC).

Helicobacter pylori Infection Synergizes with Three Inflammation-Related Genetic Variants in the GWASs to Increase Risk of Gastric Cancer in a Chinese Population

Background Three recent genome-wide association studies (GWASs) have reported that three SNPs (rs4072037, rs13361707 and rs2274223) located on genes related to host inflammatory response are significantly associated with susceptibility to gastric cancer (GC) in Chinese populations. Helicobacter pylori infection is also an important risk factor for GC through causing inflammatory response in the gastric mucosa. However, no study has established whether there are potential gene-environment interactions between these genetic variants and H. pylori infection to the risk of GC. Methods We genotyped three polymorphisms (rs4072037 at 1q22, rs13361707 at 5p13, and rs2274223 at 10q23) in 335 Chinese gastric adenocarcinoma patients and 334 controls. H. pylori serology was examined by enzyme-linked immunosorbent assay. Multivariable logistic regression models were used to evaluate the association between the variables and GC risk. Results We confirmed that the three SNPs (rs4072037, rs13361707 and rs2274223) were significantly associated with GC susceptibility. H. pylori infection also significantly increased the risk of GC. Furthermore, there were joint effects between H. pylori infection and the three SNPs on the risk of GC. The most elevated risk of GC was found in subjects with H. pylori seropositivity and AA genotypes for rs4072037 [odds ratio (OR), 3.95; 95% confidence interval (CI), 2.29–6.79], H. pylori seropositivity and CT/CC genotypes for rs13361707 (OR, 2.68; 95% CI, 1.62–4.43), H. pylori seropositivity and AG/GG genotypes for rs2274223 (OR, 2.45; 95% CI, 1.55–3.88) compared with those with H. pylori seronegativity and other genotypes of each SNP. Significant interactions were observed between H. pylori seropositivity and the three SNPs (all P G× E <0.05) to the risk of GC. Conclusion These findings indicate that the three SNPs (rs4072037, rs13361707 and rs2274223) identified in the GWASs may interact with H. pylori infection to increase the risk of GC.

Association of p53 and MDM2 polymorphisms with risk of human papillomavirus (HPV)-related esophageal squamous cell carcinoma (ESCC).

PURPOSE Though polymorphisms of the tumor suppressor gene p53 have been extensively investigated in numerous tumors, particularly tumors associated with human papillomavirus (HPV) infection. However, the results remain controversial. Our previous study showed that HPV serostatus is not an independent risk factor for esophageal squamous cell carcinoma (ESCC) in nonsmokers and nondrinkers. Given the roles of p53 and HPV E6 as well as MDM2 oncoproteins in p53 degradation, we validated the association of p53 and MDM2 polymorphisms with ESCC risk stratified by HPV16 sero-status. METHODS Single nucleotide polymorphisms of p53 Arg72Pro (rs1042522) and MDM2 (rs937283) in 307 ESCC patients and 311 healthy controls were genotyped. The presence or absence of HPV16 in serum was measured by enzyme-linked immunosorbent assay. Multivariable logistic regression analysis was used to evaluate the possible associations of p53 and MDM2 polymorphisms with ESCC risk stratified by HPV16 sero-status. RESULTS Patients carrying p53 Arg/Arg or Arg/Pro had a higher risk of esophageal SCC (P<0.001, Odds ratio [OR] 4.98, 95% confidential interval [CI] 3.46-7.17), however, not found in MDM2 rs937283. The risk of esophageal SCC increased significantly among patients carrying p53 Arg/Arg, or Arg/Pro and HPV16-seropositivity (P<0.001, OR 9.33, 95% CI 5.44-16.0), but not for MDM2 rs937283. The risk of esophageal SCC was further elevated among patients carrying Arg/Arg or Arg/Pro and HPV16-seropositivity who were smokers (P<0.001, OR 27.05, 95% CI 11.06-66.16) or drinkers (P<0.001, OR 13.20, 95% CI 5.74-30.38). CONCLUSION HPV16 seropositivity synergized with p53 Arg/Arg or Arg/Pro and increased ESCC risk, especially in smokers or drinkers.

Human papillomavirus (HPV) infection and the risk of esophageal squamous cell carcinoma

There is currently no consensus on the relationship between human papillomavirus (HPV) infection and the pathogenic process of esophageal squamous cell carcinoma (ESCC). Therefore, a retrospective study was performed to explore the association between HPV infection and ESCC, where 225 patients with diagnosed ESCC and 224 matched controls were enrolled in the study and stratified according to smoking and alcohol consumption. Enzyme-linked immunosorbent assay was used to determine seropositivity to HPV by the detection of either IgG or IgM anti-HPV antibodies. In the non-smoking and non-alcohol-consuming subgroup, the incidence of ESCC of HPV seropositive subjects was similar with that of HPV seronegative subjects (P= 0.737, odds ratio [OR] 1.14, 95% confidence interval [CI] 0.54-2.40). However, in the smoking subgroup, there was a significant difference in the incidence of ESCC between HPV seropositive subjects and HPV seronegative subjects (P= 0.009, OR 2.22, 95% CI 1.22-4.04). In addition, there was a significantly higher association of the development of ESCC in HPV seropositive patients that smoke and drink than those that do not (P < 0.001, OR 10.31, 95% CI 4.04-26.29). Therefore, HPV infection is not an independent risk factor for developing ESCC in the non-smoking and non-alcohol-consuming group. For smokers, however, HPV infection increases the risk of the incidence of ESCC.

Decreased expression of the carboxyl terminus of heat shock cognate 70 interacting protein in human gastric cancer and its clinical significance.

The carboxyl terminus of heat shock cognate 70 interacting protein (CHIP) is an E3 ubiquitin ligase, which can promote ubiquitylation and degradation of many tumor-related proteins. However, the expression of CHIP in human gastric cancer has not been investigated. In this study, the mRNA and protein levels of CHIP expression in 53 cases of gastric cancer and matched normal tissues were determined by quantitative real-time PCR, western blotting and immunohistochemistry. We showed that CHIP was registered from basal to middle portions of normal gastric mucosa. CHIP expression was notably decreased or lost in human gastric cancer samples compared with the matched normal non-cancer samples. The correlations between CHIP downregulation and the clinicopathological characteristics were also evaluated. The expression of CHIP was significantly lower in the gastric cancer samples compared to the matched normal samples at both mRNA and protein levels (P<0.05 and P<0.05, respectively). More importantly, the downregulation of CHIP was correlated with TNM stage (P=0.048) and lymph node metastasis (P=0.010) at the mRNA levels. In addition, the downregulation of CHIP was correlated with lymph node metastasis (P=0.021) and tumor differentiation (P=0.009) at the protein levels. Taken together, at both mRNA and protein levels, the decreased expression of CHIP was correlated with lymph node metastasis. Furthermore, our study suggests that a negative correlation exists between CHIP expression and tumor malignancy in human gastric cancer.

Combined effects of leukocyte telomere length, p53 polymorphism and human papillomavirus infection on esophageal squamous cell carcinoma in a Han Chinese population

Telomere shortening has been suggested to be a genetic predictor for various cancers. However, evidences about this point with respect to esophageal squamous cell carcinoma (ESCC) in Han Chinese populations remain limited. Our previous study demonstrated that p53 Arg72Pro polymorphism was associated with the risk of human papillomavirus (HPV)-related ESCC. Telomeres and p53 play important roles in maintaining genomic stability and regulating the cell cycle. HPV impacts both telomere length stabilization and p53 degradation. Given the roles of the three factors, we evaluated leukocyte telomere length, p53 variants and HPV-16 serology to examine the potential associations between them and ESCC risk in a case-control study with 308 patients and 309 cancer-free controls matched by age and sex. Compared with long telomere length, short telomere length was significantly associated with an increased risk of ESCC (adjusted OR 2.01; 95% CI 1.41-2.80). Moreover, this association was enhanced when combined with HPV-16 seropositivity and p53 Arg/Arg or Arg/Pro genotypes. Notably, individuals with short telomere length, Arg/Pro or Arg/Arg genotypes and HPV-16 seropositivity had a 12.08-fold (95% CI 5.49-26.56) increased risk of ESCC compared to those with none of the three investigated risk factors. Taken together, these results indicate that short telomere length in peripheral blood leukocytes is a biomarker for ESCC risk, and has statistically additive effects with p53 variants and HPV seropositivity with regard to the risk of ESCC in a Han Chinese population.

Predictive value of a serum-based proteomic test in non-small-cell lung cancer patients treated with epidermal growth factor receptor tyrosine kinase inhibitors: a meta-analysis

Abstract Objective: Several studies have demonstrated that a serum-based proteomic test (VeriStrat) is able to predict the clinical outcome of non-small-cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, these studies have limited power to draw a precise conclusion because of their small sample sizes and inconsistent results. Therefore, a meta-analysis was carried out in an attempt to provide more persuasive evidence. Research design and methods: Electronic searches for relevant articles in PubMed, Embase, Medline, and Web of Science published up to May 2013 were conducted. Stata Statistical Software version 12.0 was applied for statistical analysis. The combined hazard ratio (HR) and 95% confidence interval (CI) were estimated using fixed-effects models. Results: Eleven cohorts involving 706 patients collected from seven studies were subjected to final analysis. This serum-based proteomic test’s ‘good’ status predicted a better clinical outcome with a pooled HR of 0.40 (95% CI 0.32 to 0.49; p < 0.001) for overall survival (OS), and 0.49 (95% CI 0.39 to 0.60; p < 0.001) for progression-free survival (PFS). There was no significant heterogeneity, but a slight publication bias in this study. Conclusions: Our meta-analysis demonstrated that this serum-based proteomic test has a predictive value for NSCLC patients treated with EGFR-TKIs. Future data are needed to validate and update our results.

Specific targeting of nasopharyngeal carcinoma cell line CNE1 by C225-conjugated ultrasmall superparamagnetic iron oxide particles with magnetic resonance imaging

An accurate definition of clinical target volume (CTV) is essential for the application of radiotherapy in nasopharyngeal carcinoma (NPC) treatment. A novel epidermal growth factor receptor (EGFR)-targeting contrast agent (C225-USPIO) was designed by conjugating ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles with cetuximab (C225), to non-invasively define the CTV of tumor. The immunobinding activity of C225-USPIO to NPC cell line CNE1 was confirmed by flow cytometry and immunofluorescence. The time-dependent accumulation of C225-USPIO in CNE1 cells was evaluated using Prussian blue staining. Targeted internalization and subcellular localization of C225-USPIO was confirmed by transmission electron microscope. The results indicated that C225-USPIO specifically bound to EGFR on the surface of CNE1 cells and was taken up into the cell. The uptake of C225-USPIO by CNE1 cells increased significantly with time, when compared with human IgG-USPIO. In addition, 4.7 T magnetic resonance imaging (MRI) revealed that C225-USPIO had a capacity to accumulate in the CNE1 cells, with a resultant marked decrease in MRI T2-weighted signal intensity over time. These findings imply that C225-USPIO has the potential as an MRI contrast agent and can be employed to non-invasively detect early-stage NPC with EGFR overexpression. This provides sufficient theoretical basis for commencing in vivo experiments with the compound.

Pituitary metastasis from a renal cell carcinoma progressed after sorafenib treatment

Pituitary metastasis from renal cell carcinoma is rare and has never been reported for renal cell carcinoma primarily treated with sorafenib. Herein, we present a case of an advanced clear-cell renal cell carcinoma in which pituitary metastasis progressed but extracerebral metastases showed partial response to sorafenib treatment.

Genetic variants in the plasminogen activator inhibitor‐1 gene are associated with an increased risk of radiation pneumonitis in lung cancer patients

Plasminogen activator inhibitor‐1 (PAI‐1) plays a crucial role in the process of lung injury, although its association with radiation pneumonitis (RP) is unclear. We hypothesized that genetic variants in PAI‐1 may influence the risk of RP. In this study, 169 lung cancer patients were genotyped for six single‐nucleotide polymorphisms in PAI‐1 using the Sequenom MassARRAY system. The risk of RP was evaluated by Cox proportional hazards analyses. The cumulative RP probabilities by genotype were assessed using Kaplan–Meier analyses. Univariate and multivariate analyses revealed that PAI‐1:rs7242 GT/GG was correlated with an increased occurrence of grade ≥3 RP (crude hazard ratio = 3.331; 95% confidence interval, 1.168–9.497; P = 0.024). Our results indicated that PAI‐1:rs7242 in the 3′‐untranslated region of PAI‐1 can be a predictor of grade ≥3 RP before radiotherapy.