Cervical Squamous Cell Carcinoma Patients Research Articles

Role of CD44 and Lewis Y antigen in chemo-resistance of locally advanced cervical squamous cell carcinoma (LACSCC) patients.

e16590 Background: Several mechanisms are involved in the development of resistance to therapy in LACSCC. Studies have shown that CD44 and Lewis Y antigen (LeY) form a complex that is associated wi...

Sex-determining region Y-related high mobility group box (SOX)-2 is overexpressed in cervical squamous cell carcinoma and contributes cervical cancer cell migration and invasion in vitro.

Sex-determining region Y-related high mobility group box 2 (SOX-2) is a key pluripotency-associated transcription factor and may be implicated in the pathogenesis of cervical squamous cell carcinoma (SCC). The aim of this study was to explore SOX-2 expression in cervical SCC tissues and to examine whether and how SOX-2 regulates the malignant behaviors of cervical SCC cells in vitro. We here found that SOX-2 expression in the examined cervical SCC tissues was higher than that in the normal cervical and cervical intraepithelial neoplasia (CIN) tissues. Higher protein level of SOX-2 (nuclear positive staining cells ≥50 %) was detected in 34.9 % (29 out of 83 cases) of cervical SCC patients. We also noted that 100 % of well-differentiated and 66.7 % of moderately differentiated cervical SCCs showed lower SOX-2 expression (nuclear positive staining cells <50 %), while 58.8 % of poorly differentiated tumors had higher SOX-2 expression (P < 0.05). Furthermore, the migratory and invasive capabilities of SiHa cervical cancer cells were enhanced when SOX-2 was upregulated whereas suppressed when SOX-2 was downregulated. Also, the phosphorylation levels of protein kinase B (Akt) and extracellular regulated protein kinases (ERK) 1/2 were increased in SOX-2-overexpressed cancer cells but decreased in SOX-2-depleted cells. Additionally, LY294002 (Akt pathway inhibitor) or U0126 (ERK pathway inhibitor) significantly suppressed SOX-2-overexpression-induced migration and invasion in SiHa cells. Our results indicate that differentially expressed SOX-2 is associated with tumor differentiation (P < 0.05) and that SOX-2 contributes to the migratory and invasive behaviors of cervical SCC in vitro.

Transcriptome profiling of the cancer and adjacent nontumor tissues from cervical squamous cell carcinoma patients by RNA sequencing.

Cervical cancer is the third most common cancer and the fourth leading cause of cancer deaths among women in the world. The discovery of vital diagnostic and therapeutic markers against cervical squamous cell carcinoma (CSCC) would broaden our understanding on the molecular basis of CSCC. In this study, we thoroughly analyzed the transcriptome of CSCC and matched adjacent nontumor (ATN) tissue. RNA sequencing was performed to screen the differentially expressed genes (DEGs) of three pairs of CSCC and ATN tissues. Functional enrichment analysis was used to uncover the biological functions of DEGs. Protein interaction network was carried out to reveal interaction of DEGs. Quantitative real-time PCR was conducted to validate the expression of DEGs. Immunohistochemistry was used to detect the relationship between clinicopathological parameters of CSCC and DEGs. There were a total of 347 significantly common DEGs in the three paired examples, including 104 consistent upregulated and 148 consistent downregulated DEGs. The 347 DEGs were categorized into 73 functional categories by Gene Ontology (GO) analysis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis suggested six significantly signal pathways. The protein interaction network uncovered three important DEGs, including retinol dehydrogenase 12 (RDH12), ubiquitin D (UBD), and serum amyloid A1 (SAA1). We found that RDH12 expression was decreased in 74.5 % of CSCC tissues. RDH12 expression was negatively associated with tumor size and depth of cervical invasion. The UBD was overexpressed in 61.7 % of CSCC tissues and was positively related with tumor size and lymphatic metastasis. The SAA1 protein was overexpressed in 57.4 % of CSCC tissues and was positively related with clinicopathological parameters of tumor size, lymphatic metastasis, and depth of cervical invasion. The RDH12, UBD, and SAA1 genes might participate in the progression of CSCC.

The prognostic value of squamous cell carcinoma antigen for predicting tumor recurrence in cervical squamous cell carcinoma patients.

ObjectiveThe aim of this study was to evaluate the prognostic value of squamous cell carcinoma antigen (SCC-Ag) and the optimal cut-off value for predicting recurrence in cervical squamous cell carcinoma patients with complete remission after primary treatment.MethodsWe reviewed the records of 783 cervical squamous cell cancer patients who underwent primary therapy and showed complete remission at our institution between January 2000 and April 2014. A receiver operating characteristic curve was used to determine the optimal SCC-Ag threshold to predict recurrence. Cox regression model for disease free survival was used to assess differences in outcome.ResultsThe median follow-up period was 41.2 months, and 154 patients (19.7%) had recurrent disease. The median pretreatment and posttreatment SCC-Ag level was 2.6 ng/mL (range, 0.1 to 532.0 ng/mL) and 0.7 ng/mL (range, 0.0 to 46.8 ng/mL), respectively. Both pretreatment and posttreatment SCC-Ag levels were higher in the recurrence group (P=0.017 and P=0.039). Optimal cut-off value of pretreatment and posttreatment SCC-Ag for predicting recurrence was 1.86 ng/mL (area under the curve, 0.663; P=0.000), and 0.9 ng/mL (area under the curve, 0.581; P=0.002), respectively. In the multivariate Cox regression model, pretreatment SCC-Ag >1.86 ng/mL (odds ratio, 2.11; 95% confidence interval, 1.38 to 3.22; P=0.001) and posttreatment SCC-Ag >0.9 ng/mL (odds ratio, 1.64; 95% confidence interval, 1.18 to 2.28; P=0.003) were significantly associated with poor disease free survival.ConclusionPatients with pretreatment SCC-Ag >1.86 ng/mL or posttreatment SCC-Ag >0.9 ng/mL should be considered at high risk for cancer recurrence after complete remission, and therefore, closer surveillance is needed.

Relevant Role of Di-Fucosylated Ley Antigen in the Outcome of Locally Advanced Cervical Squamous Cell Carcinoma Patients Treated with Cisplatin Regimen

Background: Several mechanisms are involved in the development of resistance to therapy in LACSCC. Studies have shown that CD44 and Lewis Y antigen (LeY) form a complex that is associated with chemoresistance, tumor invasion and metastasis. We assessed the role of CD44 and LeY in the outcome of LACSCC patients (pts) treated with different chemotherapy regimens. Methods: A total of 126 LACSCC pts FIGO stages IIB-IVA were selected from GOCS databases: 74 pts included in three different prospective phase II trials in the neoadjuvant setting (vinorelbine, docetaxel, ifosfamide-vinorelbinecisplatin) and 52 pts treated with standard radio-chemotherapy based in cisplatin (RCBC). Clinical data at baseline, disease free survival (DFS) and overall survival (OS) were recorded. Univariate and multivariate Cox models were employed. Results: Median age was 45.6 years (range: 24.9 - 80.5). Sixty-three and 47 tumors were CD44+ and LeY+, respectively. Expansive growth tumors showed a higher grade (p=.0024), mitotic index (p=.0505), tumoral necrosis (p=.0191), LeY+ (p=.0034) and CD44+/LeY+ co-expression (p=.0334). CD44+ cells were present in 91.3% of those with local recurrence (p=.0317). Advanced stage was associated with LeY+ tumors (p=.0057). Pts treated with RCBC had worse DFS and OS when their tumors expressed LeY antigen (p=.0083 and p=.0137, respectively). Pre-treatment hemoglobin level, FIGO stage and tumor response remained the most significant prognostic factors in Cox regression. Conclusions: In our cohort of LACSCC pts, the co-expression of CD44+/LeY+ was not associated with worse outcome. However, in the subgroup of pts receiving RCBC, LeY expression was correlated with shorter DFS and OS.

Defective Expression of Polarity Protein Par3 Promotes Cervical Tumorigenesis and Metastasis

Objectives: The aim of this study was to investigate whether the partition-defective 3 protein (Par3) regulate cervical carcinoma growth and metastasis. Methods: Immunohistochemistry were used to analyze the expression of Par3 protein in samples from 89 cervical squamous cell carcinoma (CSCC) patients among Uighur women. The specific short hairpin (shRNA) vector as well as eukaryotic expression vector of PARD3 was transfected into SiHa cell lines. The variation of migration and invasion after transfection was detemined using Transwell assays, cell cycle and apoptosis were assayed by flow cytometry, respectively. Results: The incidence of CSCC was associated with reduced expression of Par3. Down-regulation of Par3 was significantly associated with more advanced tumors (i.e., higher histological grade, lymph node involvement, and higher tumor stages) (p<0.05 for all). Lost expression of Par3 promotes proliferation, inhibits apoptosis, and enhances migration and invasion. Loss of Par3 induces MMP9 expression and epithelial to mesenchymal transition (EMT) related genes (N-cadherin, E-cadherin and β-Catenin) expression changed in SiHa cells. Conclusions: The reduced Par3 expression in cervical cancer indicating tumor-suppressive properties of Par3 that may be a marker of poor prognosis in cervical cancer patients and the molecular determinants of epithelial polarity which have tumorigenesis enhancing impact might through EMT.

Single nucleotide polymorphisms in PDCD6 gene are associated with the development of cervical squamous cell carcinoma.

The programmed cell death 6 (PDCD6), discovered as a proapoptotic calcium-binding protein, has recently been found dysregulated in tumors of various origin and contributed to cancer cell viability. The aim of this study was to determine whether SNPs in PDCD6 are associated with cervical squamous cell carcinoma (CSCC). Polymerase chain reaction-restriction fragment length polymorphism method was used to genotype two tag SNPs (rs3756712 and rs4957014) of PDCD6 in 328 CSCC patients and 541 controls. Significantly increased CSCC risks were found to be associated with T allele of rs3756712 and G allele of rs4957014 (P=0.017, OR=1.320, and P=0.007, OR=1.321, respectively). CSCC risks were associated with these two SNPs in different genetic model (P=0.04, OR=1.78 for rs3756712 in a recessive model, and P=0.006, OR=2.01 for rs4957014 in a codominant model, respectively). Results of stratified analyses revealed that rs4957014 is associated with parametrial invasion of CSCC (P=0.044, OR=1.414). Our results suggest that these two tag SNPs of PDCD6 are associated with CSCC, indicating that PDCD6 may play an important role in the pathogenesis of CSCC.

Evaluation of the value of ENI in radiotherapy for cervical and upper thoracic esophageal cancer: a retrospective analysis.

BackgroundA retrospective study to compare the failure patterns and effects of elective nodal irradiation (ENI) or involved field irradiation (IFI) for cervical and upper thoracic esophageal squamous cell carcinoma (SCC) patients.MethodsOne hundred and sixty nine patients with the cervical and upper thoracic esophageal SCC were analyzed retrospectively; 99 patients (59%) underwent IFI and 70 patients (41%) received ENI. We defined “Out-PTVifi in-PTVeni metastasis” as lymph node metastasis occurring in the cervical prophylactic field of PTVeni thus out of PTVifi.ResultsOut-PTVifi in-PTVeni cervical node metastasis occurred in 8% of patients in the IFI group, all within 2 years after treatment. However, it occurred in 10% of patients in the ENI group, and these failures happened gradually since one year after treatments. No difference was found in OS and the incidences of Grade ≥ 3 treatment-related esophageal and lung toxicities between the two groups.ConclusionsENI for cervical and upper thoracic esophageal SCC patients did not bring longer OS and better long-term control of cervical lymph nodes. Although ENI might delay cervical nodes progression in elective field; it could not decrease the incidence of these failures.

Expression of growth‑regulated oncogene‑1, hepatocyte growth factor, platelet‑derived growth factor‑AA and soluble E‑selectin and their association with high‑risk human papillomavirus infection in squamous cell carcinoma of the uterine cervix.

The aim of the present study was to evaluate the clinical significance and prognostic value of growth‑regulated oncogene‑1 (GRO‑1), hepatocyte growth factor (HGF), platelet‑derived growth factor‑AA (PDGF‑AA), soluble E‑selectin (sE‑selectin) and high‑risk human papillomavirus (HPV; types 16, 18/45, 31 and 33/52/58/67) infection in cervical squamous cell carcinoma (CSCC). A total of 426cases were enrolled in the present study, of which 292cases were patients with CSCC, 43 were patients with cervical intraepithelial neoplasia (CIN) and 91were healthy controls. Luminex xMAP technology was used to detect the serum levels of GRO‑1, HGF, PDGF‑AA and sE‑selectin in all cases and two‑channel fluorescence quantitative polymerase chain reaction was used to determine HPV DNA in cervical scrapings from CSCC and CIN patients. The results demonstrated that the serum levels of GRO‑1, HGF and sE‑selectin were significantly higher in patients with CSCC compared with patients with CIN and the healthy controls (P<0.0001). Compared with the CIN patients, the HPV positive rate in the CSCC patients significantly increased (P=0.013). The four factors were correlated with certain clinicopathological variables of CSCC patients to a certain degree (P<0.05) and the levels of HGF were closely associated with HPV infection (P=0.039). The receiver operating characteristic curves demonstrated that HGF obtained the highest diagnostic value compared with the other three factors. Multivariate Cox regression analysis demonstrated that the serum levels of HGF (P<0.0001), FIGO stage (P<0.0001) and pelvic lymph node metastasis (P=0.001) were independent prognostic factors in patients with CSCC, while high‑risk HPV infection did not show any significance in this analysis. These results demonstrated that HGF may be a useful prognostic biomarker rather than high‑risk HPV types in patients with CSCC.

Down regulation of miR-143 is related with tumor size, lymph node metastasis and HPV16 infection in cervical squamous cancer

ObjectiveThis study is to investigate the role of miR-143 expression in cervical squamous cell carcinoma (SCC).MethodsThe expression level of miR-143 was examined by quantitative real-time PCR. Human papillomavirus (HPV) genotype was detected by HPV genotype detection kit. The expression level of bcl-2 was detected by immunohistochemistry.ResultsThe positive rate of HPV was 78% in the patients of cervical SCC. The most prevalent genotype was HPV16, with a positive rate of 42%. The expression level of miR-143 was significantly lower in the cervical SCC tissues than that in the normal cervical tissues (Z = −2.180, P = 0.029). Down-regulated miR-143 expression was associated with tumor size, lymph node metastasis and HPV16 infection in cervical cancer patients. No significant associations were found between the expression levels of miR-143 and age, clinical stage, differentiation or lymph vascular space invasion. And, in cervical SCC patients after treatment with Taxol chemotherapy, the expression level of miR-143 was higher and the positive expression of bcl-2 protein was lower. However, the differences in expression changes of miR-143 and bcl-2 were not statistically significant (miR-143, Z = −0.763, P = 0.446; bcl-2 protein, χ2 = 2.277, P = 0.131).ConclusionDown-regulated miR-143 is related with tumor size, lymph node metastasis and HPV16 infection in cervical SCC, but miR-143 does not participate in the Taxol sensitivity response.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1401279451112150.

Differentially expressed microRNAs in the serum of cervical squamous cell carcinoma patients before and after surgery

BackgroundThe purpose of this study was to detect the serum microRNAs (miRNAs) that are differentially expressed in cervical squamous cell carcinoma (SCC) patients and negative controls, with a focus on the miRNA profiles of the patients before and after surgery. The aim of the study is to evaluate the potential of these miRNAs as novel markers for the post-therapeutic monitoring of cervical SCC patients.ResultsA total of 765 serum miRNAs from 10 cervical SCC patients before surgery, 10 cervical SCC patients after surgery, and 10 negative controls were profiled using a TaqMan MicroRNA Array. A set of selected differentially expressed miRNAs were further analyzed in the patients at different perioperative periods, including preoperative, 1 week postoperative, and one month postoperative. The results showed that several serum miRNAs were differentially expressed in the cervical SCC patients compared with the negative controls, including miR-646, miR-141* and miR-542-3p. More importantly, we found that levels of specific serum miRNAs were deregulated in the pre- and postoperative stages, and these miRNAs could be useful for post-therapeutic monitoring of disease progression. Finally, we depicted a regulatory network of differentially expressed serum miRNAs, and many possible target genes were predicted in the estrogen-mediated signal pathways, supporting the hypothesis that cervical SCC is a hormone-associated gynecological disease.ConclusionsOur study demonstrated that the circulating miRNAs miR-646, miR-141* and miR-542-3p could potentially serve as non-invasive biomarkers for cervical SCC. The levels of these specific miRNAs might be useful for the post-therapeutic monitoring of disease progression. This is the first report showing that circulating miRNAs could serve as biomarkers for the therapeutic intervention of cervical SCC.

Targeting of Histone Deacetylases to Reactivate Tumour Suppressor Genes and Its Therapeutic Potential in a Human Cervical Cancer Xenograft Model

Aberrant histone acetylation plays an essential role in the neoplastic process via the epigenetic silencing of tumour suppressor genes (TSGs); therefore, the inhibition of histone deacetylases (HDAC) has become a promising target in cancer therapeutics. To investigate the correlation of histone acetylation with clinicopathological features and TSG expression, we examined the expression of acetylated H3 (AcH3), RARβ2, E-cadherin, and β-catenin by immunohistochemistry in 65 cervical squamous cell carcinoma patients. The results revealed that the absence of AcH3 was directly associated with poor histological differentiation and nodal metastasis as well as reduced/negative expression of RARβ2, E-cadherin, and β-catenin in clinical tumour samples. We further demonstrated that the clinically available HDAC inhibitors valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA), in combination with all-trans retinoic acid (ATRA), can overcome the epigenetic barriers to transcription of RARβ2 in human cervical cancer cells. Chromatin immunoprecipitation analysis showed that the combination treatment increased the enrichment of acetylated histone in the RARβ2-RARE promoter region. In view of these findings, we evaluated the antitumor effects induced by combined VPA and ATRA treatment in a xenograft model implanted with poorly differentiated human squamous cell carcinoma. Notably, VPA restored RARβ2 expression via epigenetic modulation. Additive antitumour effects were produced in tumour xenografts by combining VPA with ATRA treatment. Mechanistically, the combination treatment reactivated the expression of TSGs RARβ2, E-cadherin, P21CIP1, and P53 and reduced the level of p-Stat3. Sequentially, upregulation of involucrin and loricrin, which indicate terminal differentiation, strongly contributed to tumour growth inhibition along with partial apoptosis. In conclusion, targeted therapy with HDAC inhibitors and RARβ2 agonists may represent a novel therapeutic approach for patients with cervical squamous cell carcinoma.

Association of the Plasma and Tissue Riboflavin Levels with C20orf54 Expression in Cervical Lesions and Its Relationship to HPV16 Infection

Riboflavin deficiency can cause a variety of metabolic problems that lead to skin and mucosal disorders. Limited evidence suggests that high intake of riboflavin may reduce overall risks of cancer. However, association of this deficiency with cervical cancer and precancerous lesions are still not definitively known. In this study, we characterized the relationship between plasma and tissue riboflavin levels and C20orf54 protein expression in patients with cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) as well as the relationship of these levels with human papillomavirus virus 16, 18 (HPV16/18) infections. High-performance liquid chromatography (HPLC) was used to measure blood riboflavin levels in patients with CIN and CSCC, and an enzyme-linked immunosorbent assay (ELISA) was used to determine tissue riboflavin levels in patients with CSCC and matched normal mucous epithelia. The expression of C20orf54 in fresh CSCC and matched tissues were detected by qRT-PCR and western blot, respectively. And it was further confirmed by immunohistochemistry (IHC) with formalin-fixed, paraffin-embedded CIN and CSCC. An HPV genotyping chip was used to analyze HPV infection and typing. The results showed that patients with CIN and CSCC had decreased plasma riboflavin levels as compared with normal controls. There was also significantly decreased riboflavin in tissues from CSCC patients, when compared with normal cervical epithelia. C20orf54 expression were significantly up-regulated in CSCC compared to matched control on both mRNA and protein level. Tissue riboflavin levels were significantly lower in HPV16/18 positive tissue compared with HPV16/18-negative tissue, and an inverse association was found between tissue riboflavin levels and C20orf54 mRNA and protein expression in CSCC. Additionally, C20orf54 was significantly correlated with tumor stages. In conclusion, C20orf54 tend to play a protective role in Uyghur cervical carcinogenesis of which modulating riboflavin absorption, and it is also related with HPV infection.

Plasma-free amino acid profiling of cervical cancer and cervical intraepithelial neoplasia patients and its application for early detection

In this study, plasma-free amino acid profiles were used to investigate pre-cancerous cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) metabolic signatures in plasma. Additionally, the diagnostic potential of these profiles was assessed, as well as their ability to provide novel insight into CSCC metabolism and systemic effects. Plasma samples from CIN patients (n = 26), CSCC patients (n = 22), and a control healthy group (n = 35) were analyzed by high-performance liquid chromatography, and their spectral profiles were subjected to the t test for statistical significance. Potential metabolic biomarkers were identified using database comparisons that examine the significance of metabolites. Compared with healthy controls, patients with CIN and CSCC demonstrated lower levels of plasma amino acids; plasma levels of arginine and threonine were increased in CIN patients but were decreased in cervical cancer patients. Additionally, the levels of a larger group of amino acids (aspartate, glutamate, asparagine, serine, glycine, histidine, taurine, tyrosine, valine, methionine, lysine, isoleucine, leucine, and phenylalanine) were gradually reduced from CIN to invasive cancer. These findings suggest that plasma-free amino acid profiling has great potential for improving cancer screening and diagnosis and for understanding disease pathogenesis. Plasma-free amino acid profiles may have the potential be used to determine cancer diagnoses in the early stage from a single blood sample and may enhance our understanding of its mechanisms.

Serum microRNA expression levels can predict lymph node metastasis in patients with early-stage cervical squamous cell carcinoma

Circulating microRNA expression levels can serve as diagnostic/prognostic biomarkers in several types of malignant tumors; however, to our knowledge, there have been reports describing their value in cervical squamous cell carcinoma (SCC). In this study, we used hybridization arrays to compare the microRNA expression profiles in cervical squamous cell carcinomas (SCC) samples among patients with lymph node metastasis (LNM) or without LNM; 89 microRNAs were found to fit our inclusion criteria. Using quantitative PCR (qPCR), we examined the expression levels of these microRNAs in cervical cancer tissue, as well as in serum from patients and healthy women. We compared the expression levels between patients with LNM (n=40) and those without LNM (n=40) and healthy controls (n=20). Using regression analysis, we generated a comprehensive set of marker microRNAs and drew the fitted binormal receiver operating characteristic (ROC) curves to access the predictive value. We identified 6 serum microRNAs that can predict LNM in cervical SCC patients; these microRNAs were miR-1246, miR-20a, miR-2392, miR-3147, miR-3162-5p and miR-4484. The area under the curve (AUC) of the comprehensive set of serum microRNAs predicting LNM was 0.932 (sensitivity, 0.856; specificity, 0.850). The predictive value of the serum microRNAs was inferior to that in tissue (AUC 0.992; sensitivity, 0.967; specificity, 0.950; P=0.018). We compared the LNM predictive value of serum microRNAs and SCC antigen (SCC-Ag) by drawing fitted binormal ROC curves However, serum microRNA analysis is by far superior to serum SCC-Ag analysis (AUC 0.713; sensitivity, 0.612; specificity, 0.700; P<0.0001). Serum microRNAs are a good predictor of LNM with clinical value in early-stage cervical SCC.

Comparison of the outcome between cervical adenocarcinoma and squamous cell carcinoma patients with adjuvant radiotherapy following radical surgery: SGSG/TGCU Intergroup Surveillance

The efficacy of radiotherapy (RT) for adenocarcinoma (AC) is controversial, although patients with AC of the uterine cervix are treated in a similar manner to those with squamous cell carcinoma (SCC). This retrospective study was conducted to evaluate the efficacy of adjuvant RT for patients with AC compared to those with SCC following radical hysterectomy. A total of 820 patients with stage IB-IIB cervical cancer, who underwent type III radical hysterectomy between 1997 and 2003, were retrospectively examined; the sample included 280 patients with AC and 540 with SCC. A total of 139 patients with AC and 327 with SCC underwent adjuvant treatment. The histological type did not affect the outcome for patients with stage I disease; however, stage II patients with AC exhibited a significantly worse 5-year overall survival (OS) rate compared to those with SCC. Patients with SCC exhibited significantly higher lymph node involvement compared to those with AC in stage IB1; however, there were no differences between stages IB2 and II. Among patients with lymph node involvement, patients with AC exhibited a significantly worse 5-year survival rate compared to those with SCC (46.4 vs. 72.3%, respectively; P=0.0005). Among patients receiving adjuvant RT, those with AC recurred more frequently compared to those with SCC, particularly in the pelvic cavity, including the vaginal stump and/or pelvis (24.6 vs. 10.5%, respectively; P= 0.0022). By contrast, the histological type did not affect the incidence of recurrence in paraaortic lymph nodes and/or distant recurrence. In conclusion, RT may not suffice as an adjuvant treatment for patients with cervical AC following radical hysterectomy.

Preliminary screen of metastasis-related genes in cervical squamaous cell carcinoma

To explore the differentially expressed gene profile in cervical squamous cell carcinoma tissues with and without pelvic lymph node metastasis by microarray technique and to screen tumor metastasis-related genes. Cancer tissue samples were collected from 4 cervical squamous cell carcinoma patients with pelvic lymph metastasis and 6 patients without metastasis before the treatment. Differentially expressed gene profile was identified between cervical squamous cell carcinoma tissues with and without pelvic lymph node metastasis by NimbleGen microarray. Fluorescent real-time quantitative PCR was employed to validate the accuracy of the microarray by detecting the expression of genes picked from the differentially expressed gene profile. We screened tumor metastasis-related genes through the gene bank, PUBMED and gene ontology analysis. With the application of microarray, 329 genes were identified as markedly differentially expressed genes between cervical squamous cell carcinoma tissues with and without pelvic lymph node metastasis. Real-time PCR was in accordance with microarray. Forty-four genes associated with tumor metastasis were identified from the differentially expressed gene profile. Gene profile in cervical squamous cell carcinoma tissues associated with pelvic lymph node metastasis is preliminarily identified, indicating that lymph node metastasis of cervical squamous cell carcinoma is a process involving numerous genes.

Diagnostic value of serum VEGF level for advanced cervical cancer and its relationship with therapeutic efficacy of concurrent chemoradiotherapy

Objective To investigate the diagnostic value of serum vascular endothelial growth factor (VEGF) level for cervical cancer and its relationship with the therapeutic efficacy of concurrent chemoradiotherapy (CCRT).Methods Eighty patients with a pathologically confirmed diagnosis of advanced cervical squamous cell carcinoma (CSCC),20 patients with chronic cervicitis,and 20 healthy persons (as controls) were enrolled in the study.The CSCC patients received CCRT.All the subjects had their baseline serum VEGF levels measured by enzyme-linked immunosorbent assay (ELISA);also,the CSCC patients had their serum VEGF levels measured by ELISA at 3 months after CCRT.The relationship between the serum VEGF levels and therapeutic efficacy of CCRT was analyzed.Results The CSCC patients had a significantly higher baseline serum VEGF level than the chronic cervicitis patients and controls (237.36 μg/L vs.142.36 μg/L,t =4.03,P =0.000).The serum VEGF level was closely related to tumor stage,tumor differentiation,and lymph node metastasis.A serum VEGF level above 197.52 μg/L was the optimal cut point for diagnosing cervical cancer,with a sensitivity of 0.88 and a specificity of 0.72.The serum VEGF levels before and after CCRT showed a close relationship with the therapeutic efficacy.The patients achieving a complete remission had a significantly greater change in serum VEGF level than those with progression; the patients with high baseline serum VEGF levels had a significantly higher tumor progression or death rate than those with low baseline serum VEGF levels.Conclusions Serum VEGF level has poor diagnostic value for cervical cancer,though it is closely related to the tumor stage,tumor differentiation,and lymph node metastasis of cervical cancer.However,serum VEGF level has some predictive value for the therapeutic efficacy of CCRT in patients with cervical cancer. Key words: Vascular endothelial growth factor; Related; Cervical neoplasms/radiochemotherapy

Association between two genetic variants of CD226 gene and Cervical Squamous Cell Carcinoma: A case–control study

Cervical carcinoma is a common gynecologic tumor severely influencing the health and life quality of women worldwide. CD226, a costimulatory molecule, is mainly participated in the activation and differentiation of T cells. Recent studies have investigated the association between two genetic variants (rs763361 and rs727088) of CD226 gene and many diseases. In order to evaluate whether these two variants are associated with Cervical Squamous Cell Carcinoma (CSCC), a case–control study including 349 CSCC patients and 380 unrelated healthy controls was carried out to determine the genotypes of these two variants by using the methods of polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) and DNA sequencing methods. Significantly increased CSCC risk was observed to be associated with G allele of rs727088 locus (OR=1.422, 95% CI=1.129–1.792). We have also observed that increased CSCC risk was statistically associated with rs727088 polymorphism in a dominant model (OR=1.41, 95% CI=1.05–1.89). Results of stratified analysis revealed that both rs763361 and rs727088 polymorphisms were not associated with clinical characters. Collectively, this study supports that rs727088 polymorphism may contribute to increased CSCC susceptibility.

Metabonomic signature analysis of cervical carcinoma and precancerous lesions in women by 1H NMR spectroscopy

(1)H nuclear magnetic resonance (NMR)-based metabonomics has been used to characterize the metabolic profiles of cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC). Principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used to model the systematic variation related to patients with CIN or CSCC with healthy controls. Potential metabolic biomarkers were identified using database comparisons, and the one-way analysis of variance (ANOVA) test was used to examine the significance of the metabolites. Compared with plasma obtained from the healthy controls, plasma from patients with CIN had higher levels of very-low density lipoprotein (VLDL), acetone, unsaturated lipid and carnitine, together with lower levels of creatine, lactate, isoleucine, leucine, valine, alanine, glutamine, histidine, glycine, acetylcysteine, myo-inositol, choline and glycoprotein. Plasma from patients with CSCC had higher levels of acetate and formate, together with lower levels of creatine, lactate, isoleucine, leucine, valine, alanine, glutamine, histidine and tyrosine compared with the plasma of the healthy controls. In addition, compared with the plasma of patients with CIN, the plasma of CSCC patients had higher levels of acetate, formate, lactate, isoleucine, leucine, valine, alanine, glutamine, histidine, tyrosine, acetylcysteine, myo-inositol, glycoprotein, α-glucose and β-glucose, together with lower levels of acetone, unsaturated lipid and carnitine. Moreover, the profiles showed high feasibility and specificity by statistical analysis with OPLS-DA compared to the Thinprep cytology test (TCT) by setting the histopathological outcome as standard. The metabolic profile obtained for cervical cancer is significant, even for the precancerous disease. This suggests a systemic metabolic response to cancer, which may be used to identify potential early diagnostic biomarkers of the cancer and to establish clinical diagnostic methods.