Xiaohua Wu

Fudan University, Shanghai, Shanghai Shi, China

Are you Xiaohua Wu?

Claim your profile

Publications (27)96.9 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: A new FIGO staging system for vulvar cancer was issued in 2009. The aim of this study was to identify its value in estimating the outcome of patients with vulvar squamous cell carcinoma (VSCC) in the Chinese population. A total of 184 patients who underwent radical surgery for VSCC were recruited. Their medical records and pathology slides were reviewed. Disease reclassification was conducted according to the FIGO staging system (2009). The primary outcomes were cause-specific survival (CSS), relapse-free survival (RFS) and overall survival (OS). A total of 76 patients (41.3%) were downstaged and no patients were upstaged in the new FIGO staging system (2009). The stage distribution was as follows: stage I (99), stage II (13), stage III (65) and stage IV (7). According to CSS, the patients were classified into 4 groups: stage IA (group 1), stage IB/II/IIIA (group 2), stage IIIB (group 3), and stage IIIC/IV (group 4) (5-year CSS: 100%, 85%, 34.6% and 0%, respectively). The 5-year CSS was similar among the patients with stage IB, II and IIIA carcinomas (84.4%, 84.6% and 84.8%, respectively, p=0.986), whereas, significant decline of the CSS was found with increased substages of stages IIIA, IIIB and IIIC (84.8%, 34.6%, and 0 respectively, p<0.001). The 2009 FIGO staging system for VSCC displayed good performance for the subdivisions of stage III VSCC, but it failed to stratify survival well between stages IB, II and IIIA. Copyright © 2015. Published by Elsevier Inc.
    Gynecologic Oncology 03/2015; DOI:10.1016/j.ygyno.2015.03.001 · 3.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to introduce a new method of assuring surgical margins for abdominal radical trachelectomy (ART) and report our experience using the method. We combined transverse and perpendicular sections to assess surgical margins of specimens from RT. All surgeries from 1st August 2012 to 1st October 2013 were performed by one surgeon. The frozen section (FS) was consistently performed by a group of gynaecologic pathologists according to the detailed protocol described in this article. All cases were prepared by the same pathologist, and the slides were reviewed by two pathologists. There were 53 patients treated using the new method in our institution. The patient ages ranged from 20 to 41years old (median 32). The surgeries were performed for clinical stage IA (n=11) with LVSI and IB (n=42) tumours (40 squamous cell carcinoma, 11 adenocarcinoma, two adenosquamous and two others). In 20 (37.74%) cases, no residual tumour of the ART specimen on frozen section was observed in the specimens as it was cleared by the preceding loop electrical excision procedure (LEEP) or conization. The margins were initially reported as negative in 45 cases and positive in nine cases. In those nine cases, a second slice of cervix was removed and negative in six cases and positive again in two cases, the other one with positive nodes. The results of frozen sections were concordant with the final paraffin-embedded sections. There were no false negative intraoperative assessments. There were no recurrences after a median follow-up of 15.4months (range, 6-21months). Combining transverse and perpendicular sections to assess surgical margins of specimens from RT makes the protocol simple, reliable and produces accurate results. Copyright © 2015 Elsevier Ltd. All rights reserved.
    European Journal of Cancer 02/2015; DOI:10.1016/j.ejca.2015.01.062 · 4.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Polymorphisms in Caspase-7 (CASP7) may modulate the programmed cell death and thus contribute to cervical cancer risk. In this case-control study of 1,486 cervical cancer cases and 1,301 controls, we investigated associations between four potentially functional polymorphisms in CASP7 and cervical cancer risk and evaluated their locus-locus interaction effects on the risk. The genotype-phenotype correlation was performed by a generalized linear regression model. We found that the rs4353229 polymorphism was associated with cervical cancer risk (under a recessive model: crude OR=1.20, 95% CI=1.02-1.40). Compared with the TT genotype, the rs10787498GT genotype was associated with an increased cervical cancer risk (adjusted OR=1.19, 95% CI=1.00-1.41). Combination analysis showed that subjects with four putative risk genotypes had a 1.54-fold increased cancer risk, compared with those who carried three or less putative risk genotypes. We also observed significant locus-locus joint effects on the risk, which may be mediated by the polymorphisms regulating CASP7 mRNA expression. Subsequent multifactor dimensionality reduction and classification and regression tree analyses indicated that the CASP7 genotypes might have a locus-locus interaction effect that modulated cervical cancer risk. Out data suggest that CASP7 polymorphisms may interact to modify cervical cancer risk by a possible mechanism of regulating CASP7 mRNA expression.
    Scientific Reports 02/2015; 5. DOI:10.1038/srep09225 · 5.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mutations in 16 targetable oncogenic genes were examined using reverse transcription polymerase chain reaction (RT-PCR) and direct sequencing in 285 Chinese cervical cancers. Their clinicopathological relevance and prognostic significance was assessed. Ninety-two nonsynonymous somatic mutations were identified in 29.8% of the cancers. The mutation rates were as follows: PIK3CA (12.3%), KRAS (5.3%), HER2 (4.2%), FGFR3-TACC3 fusions (3.9%), PTEN (2.8%), FGFR2 (1.8%), FGFR3 (0.7%), NRAS (0.7%), HRAS (0.4%) and EGFR (0.4%). No mutations were detected in AKT1 or BRAF, and the fusions FGFR1-TACC1, EML4-ALK, CCDC6-RET and KIF5B-RET were not found in any of the cancers. RTK and RAS mutations were more common in non-squamous carcinomas than in squamous carcinomas (P=0.043 and P=0.042, respectively). RAS mutations were more common in young patients (<45 years) (13.7% vs. 7.7%, P=0.027). RTK mutations tended to be more common in young patients, whereas PIK3CA/PTEN/AKT mutations tended to be more common in old patients. RAS mutations were significantly associated with disease relapse. To our knowledge, this is the first comprehensive analysis of major targetable oncogenic mutations in a large cohort of cervical cancer cases. Our data reveal that a considerable proportion of patients with cervical cancers harbor known druggable mutations and might benefit from targeted therapy.
    Oncotarget 12/2014; · 6.63 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ovarian cancer is the leading cause of death from gynaecological malignancies worldwide. Here we perform a three-stage genome-wide association study (GWAS) in Han Chinese women to identify risk genetic variants for epithelial ovarian cancer (EOC). We scan 900,015 single-nucleotide polymorphisms (SNPs) in 1,057 EOC cases and 1,191 controls in stage I, and replicate 41 SNPs (Pmeta<10(-4)) in 960 EOC cases and 1,799 controls (stage II), and an additional 492 EOC cases and 1,004 controls (stage III). Finally, we identify two EOC susceptibility loci at 9q22.33 (rs1413299 in COL15A1, Pmeta=1.88 × 10(-8)) and 10p11.21 (rs1192691 near ANKRD30A, Pmeta=2.62 × 10(-8)), and two consistently replicated loci at 12q14.2 (rs11175194 in SRGAP1, Pmeta=1.14 × 10(-7)) and 9q34.2 (rs633862 near ABO and SURF6, Pmeta=8.57 × 10(-7)) (P<0.05 in all three stages). These results may advance our understanding of genetic susceptibility to EOC.
    Nature Communications 08/2014; 5:4682. DOI:10.1038/ncomms5682 · 10.74 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: The aim of this study was to compare the surgical and pathological outcomes for patients with early-stage cervical cancer after abdominal radical trachelectomy (ART) and abdominal radical hysterectomy (ARH). Methods: A prospective database of ART and ARH procedures performed in a standardized manner by the same surgical group was analyzed. The 3-segment technique was used for the accurate analysis of parametrial lymph nodes (PMLNs), and parametrial measurements were recorded by the same pathologist. Standard statistical tests were used. Result: Between August 2012 and August 2013, ART was attempted in 39 patients (28.6%), and ARH was attempted in 90 patients (71.4%). The parametrium resection length was similar with ART and ARH (44.60 vs 45.48 mm, P = 0.432), as were additional surgical and pathological outcomes, including histology, lymph node positive rate, and operation time. The PMLNs were found in 28 patients (77.78%) in the ART group and in 86 (95.56%) in the ARH group (P > 0.05). Solitary PMLN metastases were observed in 3 patients (10.71%) in the ART group and in 6 (6.98%) in the ARH group. Five (55.6%) of these 9 patients had tumors of 2 cm or greater. The ARH patients (36, 40.00%) were more likely to receive postoperative chemotherapy or radiation compared with ART patients (13, 33.33%; P = 0.017). At a median follow-up of 12 and 12.5 months (P = 0.063), respectively, there were no recurrences or deaths in the ART or ARH groups. Conclusions: Using standardized techniques, ART provides similar surgical and pathological outcomes as ARH. For the patients with tumors of 2 cm or greater, PMLNs should be examined carefully. Further prospective data are urgently needed.
    International Journal of Gynecological Cancer 07/2014; 24(7). DOI:10.1097/IGC.0000000000000185 · 1.95 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study is to investigate whether EIF4A1, EIF4E, and EIF4G1 can serve as prognostic markers for patients with cervical cancer receiving preoperative brachytherapy.
    International Journal of Gynecological Cancer 06/2014; 24(5):908-15. DOI:10.1097/IGC.0000000000000152 · 1.95 Impact Factor
  • Xiaohua Wu
    [Show abstract] [Hide abstract]
    ABSTRACT: To guarantee a better perfusion, the preservation of the uterine arteries during ART has sometimes been performed but has seldom been tested. We share the results of our tests to provoke a potentially different point of view on such uses of ART. Using computed tomography angiography (CTA), we identified the uterine blood supply in patients who underwent ART with uterine artery preserved and sacrificed. We included 26 consecutive post-ART patients from the outpatient service. The uterine arteries were preserved in 16 patients (61.5%) and ligated in 10 patients (38.5%). Out of the 26 patients studied, 17 (65.4%) were supplied by only the ovarian arteries; seven (26.9%) by one uterine artery and the contralateral ovarian artery; and only 2 (7.6%) by the uterine artery supply alone. No recanalization of the ligated uterine artery or other newly formed compensatory circulation was observed. Among the 16 patients who had preserved uterine arteries, only two (12.5%) showed identifiable bilateral uterine arteries, whereas seven (43.6%) had unilateral uterine artery occlusion and another seven (43.6%), bilateral occlusion. We had three obstetric outcomes, two of which came from the ovarian artery supplying group and one from the hybrid supplying group. The ovarian artery became the dominant supplying vessel after ART. The anatomically preserved uterine artery had a 87.5% chance of occlusion after the procedure. Moreover, the contributing uterine artery did not show any functional superiority. Thus, the benefit of preserving the uterine arteries during ART is probably very limited.
    Gynecologic Oncology 04/2014; · 3.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the clinical application of diffusion weighted imaging (DWI) in uterine cervical cancer and the apparent diffusion coefficient (ADC) value in diagnosis and predicting treatment response. Twenty-eight patients with advanced primary cervical cancer confirmed by pathology and 10 cases of normal uterine cervix as control were recruited in this prospective clinical trial. To analyze the correlation between tumor volume measured in DWI and tumor maximum diameter measured according to the RECIST criteria. To compare the ADC value differences among the uterine cervical cancer, uterine myometrium, and normal uterine cervix. To compare the ADC values in 17 cancer patients before and after treatment. The illustration of tumor boundary in DWI was superior to conventional T2WI and post-enhancement T1WI. The DWI with higher b value (2000 s/mm(2)) had a better signal-to-noise ratio. The tumor volume measured in DWI has good correlation with tumor maximum diameter according to RECIST criteria (r = 0.759, P < 0.01). When b = 800 s/mm(2), the ADC values of the uterine cervical cancer, uterine myometrium, and normal uterine cervix were (9.85 ± 1.55)×10(-3) mm(2)/s, (14.20 ± 2.80)×10(-3) mm(2)/s, and (14.14 ± 0.45) ×10(-3) mm(2)/s. When b = 2000 s/mm(2), the ADC values of the uterine cervical cancer, uterine myometrium and normal uterine cervix were (7.38 ± 0.98)×10(-3) mm(2)/s, (8.52 ± 2.38)×10(-3) mm(2)/s, and (8.60 ± 0.63)×10(-3) mm(2)/s, respectively. There were significant differences between the cervical cancer and normal cervix or uterine myometrium (P < 0.001 for both). When b = 800 s/mm(2), the ADC value was (9.85 ± 1.55)×110(-3) mm(2)/s before and (13.41 ± 2.93)×10(-3) mm(2)/s after treatment (P < 0.001). When b = 2000 s/mm(2), the ADC value was (7.38 ± 0.98)×10(-3) mm(2)/s before and (8.93 ± 1.92)×10(-3) mm(2)/s after treatment (P = 0.008). Univariate logistic regression analysis showed that 25% ADC, 50%ADC, and 75%ADC in the tumor ADC value histogram before treatment were significantly correlated to the treatment outcome of cervical cancer (P < 0.05 for all). Multivariate regression analysis showed that 25%ADC, 50%ADC, and 75%ADC in the tumor ADC value histogram before treatment were not significantly correlated to the treatment outcome of cervical cancer (P > 0.05 for all). The values of ROC curves were 25%ADC = 0.818, 50%ADC = 0.775, and 75%ADC = 0.716 (P > 0.05), however, the 25% ADC showed a relatively stronger statistical power. DWI helps to confirm the morphology and exact target zone of the tumor for radiotherapy. DWI volume measurement is well correlated with RECIST criteria, particularly in volume measurement of irregular tumors. ADC value has a potential in quantitatively monitoring treatment response and predicting outcome of cervical cancers.
    Zhonghua zhong liu za zhi [Chinese journal of oncology] 02/2014; 36(2):115-9.
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study aimed to identify prognostic factors of survival and improve treatment strategies in women diagnosed with primary malignant melanoma of the vagina. Between December 2002 and August 2011, 44 patients with lesions confined to the vagina and diagnosed with melanoma at Fudan University Shanghai Cancer Center were evaluated retrospectively. Prognostic factors were analyzed by Kaplan-Meier method. With a median follow-up time of 18.9 months (range, 6.0-94.3 months), 30 (68.2%) patients developed recurrences, whereas 21 (47.7%) died of disease. Median progression-free survival (PFS) was 14.4 months and median overall survival (OS) was 39.5 months. Depth of invasion (DOI) was significantly associated with OS (P = 0.023), and there was an obvious tendency toward improved OS with a negative lymph node status (P = 0.063). The DOI was significantly associated with lymph node status (P = 0.047). The extent of surgery (wide local excision vs radical excision) was not associated with differences in PFS or OS (P = 0.573 and P = 0.842, respectively). Longer PFS was observed in patients who received adjuvant chemotherapy and radiotherapy (P = 0.038). The prognosis of primary vaginal melanoma is dependent on the DOI and lymph node status in our study. Surgical resection of disease, especially wide local excision, should be considered as the optimal treatment when complete removal of tumor with a negative margin is possible. Adjuvant therapy may be associated with a longer PFS.
    International Journal of Gynecological Cancer 01/2014; 24(1):149-55. DOI:10.1097/IGC.0000000000000013 · 1.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: MicroRNAs(miRNAs) are involved in regulating the response of cancer cells to various therapeutic interventions, but their involvement in the chemoresistance of human cervical squamous cell carcinoma is not fully understood. We found miR-181a was significantly up-regulated in specimens from patients with chemoresistant cervical squamous cell carcinoma. In this study, we aimed to clarify the role of miR-181a in regulating the chemoresistance of cervical cancer. Two human cervical squamous cancer cell lines, SiHa and Me180, were used. Enforced expression of miR-181a enhanced chemoresistance to cisplatin in cervical cancer cells through apoptosis reversion. In a nude mouse xenograft model, the overexpression of miR-181a markedly inhibited the therapeutic response to cisplatin. PRKCD, a target gene of miR-181a and a promoter of apoptosis, was negatively regulated by miR-181a. We found that the effect of miR-181a on chemoresistance was mediated by PRKCD. Additionally, silencing of PRKCD yielded an effect similar to that of miR-181a up-regulation and inhibited apoptosis in cervical cancer cells. Our findings suggest that miR-181a may function as an oncogene and induce chemoresistance in cervical squamous cell carcinoma cells at least in part by down-regulating PRKCD, thus may provide a biomarker for predicting chemosensitivity to cisplatin in patients with cervical squamous cancer.
    Experimental Cell Research 10/2013; 320(1). DOI:10.1016/j.yexcr.2013.10.014 · 3.37 Impact Factor
  • Jin Li, Xiaohua Wu, Xiaoqiu Li, Xingzhu Ju
    [Show abstract] [Hide abstract]
    ABSTRACT: As abdominal radical trachelectomy (ART) has become a favored fertility-sparing procedure, the relative contraindication of a tumor ≥ 2cm in size has been questioned. The aim of the study was to report the surgical and oncological safety of ART for selected patients with cervical cancer ≥ 2cm in size. We conducted a retrospective review of a prospectively maintained database of patients undergoing ART at our institution from 04/2004 to 01/2013. The largest tumor dimension was determined by physical exam, MRI or final pathology. Clinical and pathological data were tabulated. All patients were followed postoperatively. Of the133 patients who underwent planned ART, sixty-two (46.6%) had tumors ≥ 2cm in size (2- 4 cm). Forty-six patients were documented by exam or MRI, while 16 were documented by pathology reports. The mean age was 30.4 years, and 42 patients (67.7%) were nulliparous. Fifty (80.7%) had squamous carcinoma, 7 (11.3%) adenocarcinoma, and 5 (8%) adenosquamous carcinoma. Due to frozen-section results, 6 (9.7%) patients underwent an immediate hysterectomy. Due to high-risk features on final pathology, 27(43.5%) were treated with adjuvant chemotherapy (n=20) or chemoradiation (n=7). In total, 55 of 62 (88.7%) patients with a tumor ≥ 2cm in size preserved their fertility potential. Among these patients, 35 underwent ART without further adjuvant treatment. At a median follow-up of 30.2 months, there were no recurrences. Expanding the ART inclusion criteria to cervical cancers ≥ 2cm in size allows a fertility-sparing procedure in young women who would have otherwise been denied the option with no apparent compromise in oncological outcome. However, this may result in higher rates of conversion to hysterectomy or the need for adjuvant chemotherapy/ or chemoradiation.
    Gynecologic Oncology 07/2013; 131(1). DOI:10.1016/j.ygyno.2013.07.079 · 3.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: DNA Polymerase ζ (Polζ), an error-prone DNA polymerase involved in translesion DNA synthesis, plays a significant role in the cytotoxicity, mutagenicity, and chemoresistance of several cancers. To evaluate the association of Polζ with chemoradiation resistance and prognosis in cervical cancer, we enrolled 123 patients with squamous cell carcinoma of cervical cancer, who had adjuvant concurrent chemoradiation therapy after radical surgery treated at Fudan University Shanghai Cancer Center between 2008 and 2009, and tested their in vitro tumor inhibition rates using the 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide method and Polζ protein expression in paraffin-embedded tissues using immunohistochemistry. We found that the Polζ-positive expression was detected in 22 % of the cases. The median in vitro inhibition rate of tumor cell growth by cisplatin, carboplatin, nedaplatin, and oxaliplatin was 80, 37, 78, and 51 %, respectively. Among the tumor-related variables, FIGO stage, tumor grade, and Polζ protein expression (adjusted HR 6.7, 4.2 and 6.7; 95 % CI 1.7-26.3, 1.0-17.3 and 1.8-25.4; P = 0.007, 0.046 and 0.005, respectively) were found to be significant predictors for recurrence. Kaplan-Meier survival estimates showed that the patients with more advanced stage (IIB) or Polζ-positive expression had a significantly shorter progression-free survival. Polζ-positive expression was significantly associated with depth of cervical stromal invasion (P = 0.012). However, the association between Polζ expression and in vitro tumor inhibition rates was not significant. Taken together, Polζ expression can be used as the predictor for poor prognosis, which might be caused by the potential chemoradiation resistance of the cervical cancer patients. The mechanism deserves further exploration.
    Medical Oncology 06/2013; 30(2):500. DOI:10.1007/s12032-013-0500-4 · 2.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE: To characterize the clinicopathological features and evaluate the treatment outcomes for cases of primary extramammary Paget's disease of the vulva (EMPDV). METHODS: The medical records and pathology slides were reviewed and analyzed for 43 patients with primary EMPDV. RESULTS: The mean age of the patients was 68.6years (range, 52-85). Intraepithelial EMPDV,invasive EMPDV and EMPDV with adnexal adenocarcinoma were observed in 33 (76.7%), 7 (16.3%) and 3 (7.0%) cases, respectively. Varied surgical procedures were initially performed in 35 (81.4%) cases. A positive incision margin was observed in 16 cases (47.0%). Definitive radiotherapy at a median dose of 60Gy was performed in 8 (18.6%) patients. Six patients received postoperative radiotherapy due to a positive margin or lymph node metastasis after surgical excision. During a follow-up period of 6-169months (median, 54), recurrence was observed in 12 (34.3%) patients. Nine (75.0%) patients underwent repeated surgery and 3 (25.0%) patients received radiotherapy. Long-term overall survival was observed in patients with intraepithelial EMPDV. The median overall survival was 124.5months in intraepithelial cases, 70.8months in invasive cases and 21.3months in cases with adnexal adenocarcinoma (Log rank, P=0.032). CONCLUSIONS: Intraepithelial EMPDV accounted for the majority of primary cases and had a better prognosis. Surgical excision was the standard curative treatment for EMPDV. Radiotherapy was an alternative choice for patients with medical contradiction or surgical difficulties. Postoperative radiotherapy could be considered in cases with positive surgical margin or lymph node metastasis. Recurrence was common and repeated excision was often necessary.
    Gynecologic Oncology 02/2013; DOI:10.1016/j.ygyno.2013.02.029 · 3.69 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: MicroRNA (miRNA)-related single nucleotide polymorphisms (SNPs) may compromise miRNA binding affinity and modify mRNA expression levels of the target genes, thus leading to cancer susceptibility. However, few studies have investigated roles of miRNA-related SNPs in the etiology of cervical carcinoma. METHODS: In this case-control study of 1,584 cervical cancer cases and 1,394 cancer-free female controls, we investigated associations between two miR-218-related SNPs involved in the LAMB3-miR-218 pathway and the risk of cervical carcinoma in Eastern Chinese women. RESULTS: We found that the pri-miR-218 rs11134527 variant GG genotype was significantly associated with a decreased risk of cervical carcinoma compared with AA/AG genotypes (adjusted OR=0.77, 95% CI=0.63-0.95, P=0.015). However, this association was not observed for the miR-218 binding site SNP (rs2566) on LAMB3. Using the multifactor dimensionality reduction analysis, we observed some evidence of interactions of these two SNPs with other risk factors, especially age at primiparity and menopausal status, in the risk of cervical carcinoma. CONCLUSIONS: The pri-miR-218 rs11134527 SNP was significantly associated with the risk of cervical carcinoma in Eastern Chinese women. Larger, independent studies are warranted to validate our findings.
    BMC Cancer 01/2013; 13(1):19. DOI:10.1186/1471-2407-13-19 · 3.32 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: TNFAIP8 is an anti-apoptotic and pro-oncogenic signaling molecule involved in the process of immunity, carcinogenesis and tumor progression. Single nucleotide polymorphisms (SNPs) at microRNA binding sites may change mRNA target gene function, thus leading to cancer susceptibility and tumor progression. In this study of 1,584 cervical cancer cases and 1,394 cancer-free female controls, we investigated associations between three potentially functional SNPs in TNFAIP8 family genes and cervical cancer risk as well as platinum resistance and clinical outcomes in Eastern Chinese women. We found that the TNFAIP8-rs11064 variant GG genotype was associated with an increased risk of cervical cancer compared with AA/AG genotypes (adjusted OR=2.16, 95% CI=1.16-4.03, P=0.015). Further in vitro and ex vivo functional experiments demonstrated that the TNFAIP8-rs11064 variant G allele weakened the binding affinity of miR-22 to TNFAIP8 3'-UTR in four cancer cell lines, resulting in increased production of the TNFAIP8 protein in the patients' cervical tissues. In the survival subset, the high TNFAIP8 protein expression was significantly associated with both resistances to cisplatin and nedaplatin and recurrence and death from cervical cancer. Taken together, although lacked information on human papillomavirus (HPV) infection, the TNFAIP8-rs11064 SNP may function by affecting the affinity of miR-22 binding to the 3'-UTR of TNFAIP8 and regulating TNFAIP8 expression, thus contributing to cervical cancer risk. Additionally, the increased TNFAIP8 protein expression may predict platinum resistance and clinical outcomes in cervical cancer patients. Larger, prospective studies with detailed HPV infection data are warranted to validate our findings.
    Carcinogenesis 01/2013; DOI:10.1093/carcin/bgt001 · 5.27 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Interleukin 6 (IL6) encodes a cytokine protein, which functions in inflammation, maintains immune homeostasis and plays important roles in cervical carcinogenesis. Single nucleotide polymorphisms (SNPs) in IL6 that cause variations in host immune response may contribute to cervical cancer risk. In this two-stage case-control study with a total of 1,584 cervical cancer cases and 1,768 cancer-free female controls, we investigated associations between two IL6 SNPs and cervical cancer risk in Eastern Chinese women. In both Study 1 and Study 2, we found a significant association of the IL6-rs2069837 SNP with an increased risk of cervical cancer as well as in their combined data (OR 1.27 and 1.19, 95 % CI 1.08-1.49 and 1.04-1.36, P = 0.004 and 0.014 for dominant and additive genetic models, respectively). Furthermore, rs2069837 variant AG/GG carriers showed significantly higher levels of IL6 protein than did rs2069837 AA carriers in the target tissues. Using multifactor dimensionality reduction (MDR) and classification and regression tree (CART) analyses, we observed some evidence of interactions of the IL6 rs2069837 SNP with age at primiparity and menopausal status in cervical cancer risk. We concluded that the IL6-rs2069837 SNP may be a marker for susceptibility to cervical cancer in Eastern Chinese women by a possible mechanism of altering the IL6 protein expression. Although lacked information on human papillomavirus (HPV) infection, our study also suggested possible interactions between IL6 genotypes and age at primiparity or menopausal status in cervical carcinogenesis. However, larger, independent studies with detailed HPV infection data are warranted to validate our findings.
    Human Genetics 11/2012; 132(3). DOI:10.1007/s00439-012-1245-4 · 4.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to compare the amplification patterns of the human telomerase RNA gene (hTERC) in invasive cervical carcinomas (ICC) and cervical intraepithelial neoplasia grade III (CIN III) and to define their potential clinical implications. Cervical liquid-based cytological (LBC) specimens were collected from 53 squamous cell carcinomas (SCC), 14 CIN III, and 20 normal controls. Copy numbers of the hTERC gene were measured by fluorescence in situ hybridization (FISH) using a dual-color probe containing the hTERC probe and the control, chromosome 3 centromere-specific probe (CSP3). Nucleus with abnormal FISH pattern for hTERC was observed in 0.94-90.65% of SCC cells and in 0-85.59% of CIN III cells. Using the threshold of 5.89%, the occurrence of hTERC amplification in SCC and CIN III was similar (90.6% vs. 85.7%, P = 0.630). However, the median percentage of cells with extra gains of hTERC (hTERC:CSP3 > 1) in SCC was higher than in CIN III (64.3% vs. 31.7%, P = 0.001). Among those cells, the 3:2 signal pattern was the leading pattern for both SCC and CIN III; high-level amplification of hTERC was more common in SCC than in CIN III (60.9% vs. 48.9%, P = 0.002). In SCC, it was not found that extra gains of hTERC were associated with any clinicopathological parameters. Thus, hTERC amplification was common in cervical exfoliated cells from SCC and CIN III. More complex amplification patterns of hTERC were present in ICC. Clinical usefulness of hTERC amplification in LBC samples was limited in ICC. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.
    Diagnostic Cytopathology 10/2012; 40(10):849-55. DOI:10.1002/dc.21635 · 1.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE: Despite evidence that oestrogen may play an important role in the carcinogenesis of cervical cancer, its action and mechanism in cervical cancer invasion are not well defined. STUDY DESIGN: The invasion induced by 17β-oestradiol (E2) was measured by invasion assay. Real-time polymerase chain reaction (PCR), Western blot, enzyme-linked immunosorbent assay (ELISA) and gelatin zymography were used to study the role of E2 on metastasis-related proteases. The signal pathway was also investigated. RESULTS: E2 was found to significantly enhance the invasion of cervical cell lines including HeLa, CaSki and SiHa cells, but not C33A cells. Moreover, E2 10(-8)M increased the expression and activation of matrix metalloproteinases (MMP-2 and MMP-9) in HeLa and CaSki cells, as shown by real-time PCR, Western blot, ELISA and gelatin zymography. The expression of tissue inhibitor of metalloproteinases (TIMP-1 and TIMP-2) was decreased significantly by E2. Pretreatment with GM6001 10μM (total MMP inhibitor) or SB-3CT 20μM (specific gelatinase inhibitor) blocked the pro-invasive effect of E2. E2 was found to induce invasion via the phosphatidylinositol 3-kinase (PI3K) signalling pathway. CONCLUSION: E2 may contribute to cervical cancer metastasis through activation of proteolysis and increased invasion via the PI3K pathway.
    European journal of obstetrics, gynecology, and reproductive biology 08/2012; 165(2). DOI:10.1016/j.ejogrb.2012.07.026 · 1.97 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Patients with stage IB2 to IIA cervical cancer have a poor survival regardless of what primary treatment is performed. We conducted a study to demonstrate whether neoadjuvant treatment could offer survival benefits to those patients. Between January 2006 and December 2009, 123 patients with stage IB2 to IIA cervical cancer were enrolled and randomly assigned to receive 1 of the following 4 treatments: radical surgery alone (arm RS), brachytherapy with a total dose of 15Gy to point A followed by radical surgery (arm BT), intravenous chemotherapy with cisplatin 50 mg/m plus 5-fluorouracil 750 mg/m at a 2-week interval for 2 courses followed by radical surgery (arm IVCT), or intra-arterial chemotherapy with the same regimen as the IVCT arm followed by radical surgery (arm IACT). Two weeks after neoadjuvant treatment, all patients underwent evaluation for response and operability. Those who were not amenable to surgery received concurrent chemoradiotherapy. With a mean follow-up of 34.8 months, 120 patients were evaluable. Baseline characteristics were similarly distributed in the 4 arms. Clinical overall response rates were 61.3%, 42.9%, and 79.3% in the BT, IVCT, and IACT groups, respectively. Two patients achieved pathological complete response. Three-year progression-free survival rates were 70.7%, 66.3%, 81.5%, and 79.7% in the RS, BT, IVCT, and IACT arms, respectively (P = 0.354). Three-year overall survival was 73.3%, 68.3%, 82.9% and 80.4%, respectively (P = 0.431). Multivariate analysis showed that only lymph node status correlated with progression-free survival. Neoadjuvant treatment had no significant impact on the outcomes of patients with stage IB2 to IIA cervical cancer.
    International Journal of Gynecological Cancer 02/2012; 22(2):296-302. DOI:10.1097/IGC.0b013e31823610a1 · 1.94 Impact Factor

Publication Stats

128 Citations
96.90 Total Impact Points

Top co-authors View all

Institutions

  • 2005–2015
    • Fudan University
      • Department of Oncology
      Shanghai, Shanghai Shi, China
  • 2013
    • Shanghai Cancer Institute
      Shanghai, Shanghai Shi, China