Mingrong Xi

Common genetic polymorphisms in pre-microRNAs and risk of cervical squamous cell carcinoma.

MicroRNAs (miRNAs) function as gene regulator and they participate in diverse biological pathways. Common single nucleotide polymorphisms (SNPs) in pre‐microRNAs may change their property through altering miRNAs expression and/or maturation. We conducted a pilot study to test whether SNPs in pre‐microRNAs were associated with cervical squamous cell carcinoma (CSCC). Genotypes of three SNPs in pre‐miRNAs (hsa‐miR‐196a2 rs11614913 C/T, hsa‐miR‐499 rs3746444 A/G, and hsa‐miR‐146a rs2910164 G/C) in 226 CSCC patients and 309 control subjects were determined with the use of PCR‐restriction fragment length polymorphism (RFLP) assay. Significantly increased CSCC risks were found to be associated with G allele of rs3746444 and G allele of rs2910164 (P = 0.017, OR = 1.454, and P = 0.016, OR = 1.355, respectively). Increased CSCC risks were associated with them in different genetic model (P = 0.0004, OR = 1.98 for rs3746444 in an overdominant model, and P = 0.024, OR = 2.10 for rs2910164 in a codominant model, respectively). Results of stratified analyses revealed that rs2910164 is associated with tumor differentiation and lymph node status (P = 0.043, OR = 2.08, and a borderline P = 0.057, OR = 0.41, respectively). No association between rs11614913 and CSCC risk was observed. The present study provides evidence that rs3746444 and rs2910164 are associated with CSCC, indicating that common genetic polymorphisms in pre‐microRNAs contribute to the pathogenesis of CSCC. Mol. Carcinog.

Association between IL17 Polymorphisms and Risk of Cervical Cancer in Chinese Women

Interleukin-17 (IL-17) is a proinflammatory cytokine that is associated with inflammation, autoimmune disorders, and even tumors. Previous studies revealed that a large group of human malignant tumors have abnormally high IL-17 expression. In the present study, we analyzed two single-nucleotide polymorphisms (SNPs) in the IL17A (rs2275913) and IL17F (rs763780) in 311 cervical cancer patients and 463 controls using TaqMan assays. Our results indicated that the frequencies of AA genotype and A allele of rs2275913 were significantly different between the cervical cancer patients and controls (P = 0.008, OR = 1.32, 95% CI, 1.07–1.62). Stratified analyses revealed that the polymorphism of rs2275913 was also associated with positive peritumor intravascular cancer emboli and high clinical stage. The genotype and allele frequencies of rs763780 did not show any difference between patients and controls or relate to patient clinical characteristics. Collectively, these findings suggested that IL17 gene polymorphism rs2275913 was associated with the susceptibility as well as positive peritumor intravascular cancer emboli and high clinical stage of cervical cancer in Chinese women.

Detection of serum human epididymis secretory protein 4 in patients with ovarian cancer using a label-free biosensor based on localized surface plasmon resonance.

Background Detection of the human epididymis secretory protein 4 (HE4) biomarker plays an important role in the early diagnosis of ovarian cancer. This study aimed to develop a novel localized surface plasmon resonance (LSPR) biosensor for detecting HE4 in blood samples from patients with ovarian cancer. Methods Silver nanoparticles were fabricated using a nanosphere lithography method. The anti-HE4 antibody as a probe, which can distinctly recognize HE4, was assembled onto the nanochip surface using an amine coupling method. Detection was based on the shift in the extinction maximum of the LSPR spectrum before and after the HE4-anti-HE4 antibody reaction. These nanobiosensors were applied to detect HE4 in human serum samples and compare them using an enzyme-linked immunosorbent assay. Results Tests relating to the detection of HE4 demonstrated that the LSPR-based biosensor featured a fast detection speed, good specificity, effective reproducibility, and long-term stability. The linear range for LSPR was between 10 pM and 10,000 pM, with a detection limit of 4 pM. An excellent correlation between LSPR and enzyme-linked immunosorbent assay results was observed in human serum. Conclusion This study is the first clinical diagnostic application of the LSPR biosensor in ovarian cancer. The LSPR biosensor, a rapid, low-cost, label-free and portable screening tool, can serve as a very effective alternative for the clinical serological diagnosis of ovarian cancer.

Association of interleukin-23 receptor gene polymorphisms with risk of ovarian cancer

Among gynecological malignancies, ovarian cancer is the leading cause of death. The overall 5-year survival rate remains poor, and the pathogenesis is unknown. The interleukin-23 receptor (IL23R) is known to be critically involved in the carcinogenesis of different malignant tumors. To assess the role of IL23R in ovarian cancer, we conducted a study to investigate the polymorphisms of the IL23R gene in 96 Han Chinese women with histologically proven ovarian cancer. Polymerase chain reaction-restriction fragment length polymorphism was used for genotyping. In all three single nucleotide polymorphisms of IL23R studied, the distribution of genotype and allele frequencies of rs10889677 differed significantly between patients and controls. The frequency of allele C of rs10889677 was significantly increased in cases compared with controls (0.281 vs. 0.183, odds ratio OR=1.752, 95% confidence interval CI=1.107-2.772). Furthermore, when stratified by tumor stage, we found that the allele frequencies of rs11465817 differed significantly between FIGO stage I+II and III+IV. The higher frequency of allele A was significantly associated with advanced ovarian cancer (P=0.027, OR=2.087, 95% CI=1.083-4.023). These findings indicate that IL23R polymorphisms may play an important role in the susceptibility and prognosis of ovarian cancer in the Chinese population.

a reusable localized surface plasmon resonance biosensor for quantitative detection of serum squamous cell carcinoma antigen in cervical cancer patients based on silver nanoparticles array

Squamous cell carcinoma antigen (SCCa), as a tumor biomarker, plays an important role in adjuvant diagnosis, treatment evaluation, and prognosis prediction for cervical cancer patients. Localized surface plasmon resonance (LSPR) technique based on noble metal nanoparticles bypasses the disadvantages of traditional testing strategies, in terms of free-labeling, short assay time, good sensitivity, and selectivity. Herein, we develop a novel and reusable LSPR biosensor for the detection of SCCa. First, a triangle-shaped silver nanoparticle array was fabricated using the nanosphere lithography method. Next, we investigated and verified the feasibility of amino coupling method using 11-mercaptoundecanoic acid (MUA) to form a functionalized chip surface with monoclonal anti-SCCa antibodies on the silver nanoparticles for distinct detection of SCCa. Different concentrations of SCCa were successfully tested in both buffer and human serum by the ultrasensitive and specific LSPR system, with a linear quantitative detection range of 0.1–1,000 pM under optimal conditions. With appropriate regeneration solution, for example 50 mM glycine-HCl (pH 2.0), the LSPR biosensor featured effective fabrication reproducibility, which reduced both production cost and testing time. Our study represents the first application of the LSPR biosensor in cervical cancer, and demonstrates that the rapid, simple, and reusable nanochip can serve as a potential alternative for clinical serological diagnosis of SCCa in cervical cancer patients.

Prognostic value of IL-27 polymorphisms and the susceptibility to epithelial ovarian cancer in a Chinese population

This study investigated the association between IL-27 gene polymorphisms and susceptibility to epithelial ovarian cancer in a Chinese population and discusses the risk factors associated with survival time. We collected data on 229 patients diagnosed with epithelial ovarian cancer, from 15 to 77 years of age with a long clinical follow-up period. Polymerase chain reaction-restriction fragment length polymorphism was performed to determine the genotype of IL-27 gene polymorphisms. Ovarian cancer-specific survival (OCSS) according to genotype of IL-27 gene polymorphisms was explored by Kaplan–Meier analysis and Cox proportional hazards modeling. Significant differences for genotype frequencies of both SNP sites were found between cases and controls. Both allele G frequencies were significantly greater among the cases (rs153109: 0.404 vs. 0.303, P = 0.001, odds ratio [OR] = 1.333, 95% confidence interval [CI] = 1.133–1.567; rs17855750: 0.146 vs. 0.083, P = 0.001, OR = 1.766, 95% CI = 1.258–2.481). Haplotype analysis showed haplotypes AG, GT and GG were associated with increased ovarian cancer susceptibility while AT was a protective haplotype. Advanced FIGO stage (stages III + IV) and non-optimal cytoreductive surgery (residual tumor ≥1 cm) were poor prognostic factors in the univariate analysis (P = 0.003, P = 0.049). However, FIGO stage was found to be the only independent significant prognostic factor by Cox proportional hazards analysis (P = 0.042). IL-27p28 mRNA expression was significantly decreased in ovarian cancer patients (P < 0.0001), while no significant relationship was found between IL-27p28 mRNA expression and polymorphism of rs153109 and rs17855750 (P = 0.193 and P = 0.146, respectively). Our study suggests that IL-27 gene polymorphisms may be involved in the susceptibility to epithelial ovarian cancer, but not in survival in a clinic-based Chinese population. Haplotype analysis of these two SNPs seems to be an important mark to predict the disease susceptibility. Advanced FIGO stage, as the only significant, independent risk factor, predicts poor clinical outcomes for patients diagnosed with epithelial ovarian cancer. The decreased expression of IL-27p28 mRNA in ovarian cancer might indicate the antitumor activities of this novel cytokine.

Clinical application of a novel sliver nanoparticles biosensor based on localized surface plasmon resonance for detecting the microalbuminuria

In order to explore the clinical application of the nanobiosensor based on localized surface plasmon resonance (LSPR), we used our LSPR biosensor to detect the microalbuminuria in this work. The sliver nanoparticles were fabricated by using nanosphere lithography. The anti-human albumin antibody was immobilized on the sensor surface by amine coupling method. The different concentrations of commercial albumin and albumin in urine samples from three mild preeclampsia patients were determined according to the peak of LSPR extinction spectra. Under optimum conditions, our results showed that the biosensor displayed a detection limit of 1 ng/ml and wide dynamic range of 1 ng/ml to 1 μg/ml. Furthermore, the microalbuminuria of three patients was determined by our biosensor within a short assay time, without sample purification. This biosensor proposed herein is easy to prepare and could be used for low-cost, rapid, label-free, and sensitive screening of the microalbuminuria. This approach provides a promising platform for developing clinical diagnostic applications.

Diaphragmatic hernia during pregnancy: A case report with a review of the literature from the past 50 years

Diaphragmatic hernia is a rare complication during pregnancy. Only 30 reports have been published on this subject in English between 1959 and 2009. Due to misdiagnoses and management delays, diaphragmatic hernia usually presents itself as a life‐threatening emergency. Here, we present a case report of a patient with a traumatic diaphragmatic hernia who became acutely symptomatic during pregnancy. The diaphragmatic hernia was managed successfully, and we describe the presentation, management and outcome of this case. We also present a review of all of the reported cases of diaphragmatic hernias complicating pregnancy that have been published in English during the past 50 years.

Association of Signal Transducer and Activator of Transcription 3 Gene Polymorphisms with Cervical Cancer in Chinese Women

Signal transducer and activator of transcription (STAT) plays an important role in regulating cell proliferation, differentiation, and apoptosis. Previous studies revealed that abnormal expression/activation of STAT family members were present in a large group of human malignant tumors. In the present study, using polymerase chain reaction (PCR)-restriction fragment length polymorphism, DNA sequencing, and Taqman probe real-time PCR techniques, we analyzed two single-nucleotide polymorphisms (SNPs) in the STAT5B and STAT3 genes (rs6503691 and rs4769793, respectively) in 275 Chinese cervical cancer patients and 340 controls. Our results indicated that the genotype and allele frequencies of SNP rs4769793 were significantly different between the cervical cancer patients and normal subjects (p < 0.05, odds ratio = 1.35, 95% confidence interval = 1. 07-1.70). In addition, stratified analyses revealed that the polymorphism of rs4769793 was also associated with poor tumor differentiation and positive parametrial invasion (p < 0. 05). In contrast, SNP rs6503691 did not show any difference between patients and controls or association with patient clinical characteristics. Collectively, these findings suggested that STAT3 gene polymorphism (rs4769793) was associated with the susceptibility as well as poor differentiation and parametrial invasion of cervical cancer in Chinese women.

Interleukin 17 induces up-regulation of chemokine and cytokine expression via activation of the nuclear factor κB and extracellular signal-regulated kinase 1/2 pathways in gynecologic cancer cell lines.

Objectives Previous studies have revealed that interleukin 17 (IL-17) contributes to pathological processes in many solid tumors. However, the roles of IL-17 in gynecologic cancer still remain elusive, hindering the deep understanding of gynecologic tumorigenesis. Methods In the present study, to delineate the functional roles of IL-17 in gynecologic cancer, IL-17 stimulation was introduced in cell lines of 3 gynecologic cancers, and IL-17–induced expression of chemokines and cytokines and possible signaling pathways were investigated. Results Our results showed that in HEC-1-B (human endometrial cancer) cells, IL-17 stimulation induced mRNA level increases of CCL2, CCL5, CCL20, CXCL2, and IL-8. Similar treatment in HeLa cells caused increases in the mRNA levels of CCL2, CXCL2, IL-6, and IL-8, and in SKOV3 cells, mRNA levels of CCL2, CCL20, CXCL1, CXCL2, IL-6, and IL-8 increased. The increases in mRNA levels induced by IL-17 were dose- and time-dependent. Furthermore, with the addition of the NF-κB (nuclear factor κ–light-chain–enhancer of activated B) and extracellular signal–regulated kinase inhibitors pyrrolidine dithiocarbamate and PD98059, the IL-17–induced CCL2 mRNA level was significantly compromised. IL-17 stimulation also activated phosphorylation of IκB&agr; and extracellular signal–regulated kinase 1/2 in a time-dependent manner. Conclusion These results demonstrated that IL-17 may regulate chemokines and cytokines in gynecologic cancers.