Identifying Comprehensive Genomic Alterations and Potential Neoantigens for Cervical Cancer Immunotherapy in a Cohort of Chinese Squamous Cell Carcinoma of the Cervix

Objective Genomic alterations and potential neoantigens for cervical cancer immunotherapy were identified in a cohort of Chinese patients with cervical squamous cell carcinoma(CSCC).Methods Whole-exome sequencing was used to identify genomic alterations and potential neoantigens for CSCC immunotherapy.RNA Sequencing was performed to analyze neoantigen expression.Results Systematic bioinformatics analysis showed that C>T/G>A transitions/transversions were dominant in CSCCs.Missense mutations were the most frequent types of somatic mutation in the coding sequence regions.Mutational signature analysis detected signature 2,signature 6,and signature 7 in CSCC samples.PIK3CA,FBXW7,and BICRA were identified as potential driver genes,with BICRA as a newly reported gene.Genomic variation profiling identified 4,960 potential neoantigens,of which 114 were listed in two neoantigen-related databases.Conclusion The present findings contribute to our understanding of the genomic characteristics of CSCC and provide a foundation for the development of new biotechnology methods for individualized immunotherapy in CSCC.

Mechanisms of Sophora flavescens in the treatment of cervical squamous cell carcinoma based on comprehensive biological analysis,network pharmacology,and experimental verification

Objective:This study used comprehensive bioinformatics analysis and network pharmacology analysis to investigate the potentially relevant mechanisms of Sophora flavescens against cervical squamous cell carcinoma.Methods:Consistently altered genes involved in cervical squamous cell cancerization were analyzed in the GEO database.The chemical ingredients and target genes of Sophora flavescens were explored using the TCMSP database.We obtained the potential therapeutic targets of Sophora flavescens by intersecting the above genesets and validated them in the GEPIA database.The interaction between Sophora flavescens and target genes was predicted by molecular docking.RT-qPCR was used to verify the changes of target genes in HeLa cells treated with Sophora flavescens.Single-gene GSEA functional analysis were performed to determine the molecular mechanisms.Results:Fifteen genes related to the transformation of cervical squamous cell carcinoma were identified,among which AR and ESR1 were confirmed as targets for kaempferol,wighteone,formononetin,and phaseolinon.These compounds are the active ingredients in Sophora flavescens.Low expressions of AR and ESR1 correlate with a poor prognosis,while Sophora flavescens treatment increases the expression of AR and ESR1 in HeLa.GSEA analysis showed that AR and ESR1 mainly participate in the epithelial-mesenchymal transition in cervical squamous cell carcinoma.Conclusion:Sophora flavescens exert anti-tumor effects by targeting AR and ESR1,which may regulate cancer metastasis.

Nomograms based on HPV load for predicting survival in cervical squamous cell carcinoma: An observational study with a longterm follow-up

Objective: To investigate the prognostic value of pretreatment human papillomavirus(HPV) viral load for cervical cancer, and to develop nomograms based on HPV load and other clinicopathological factors for long-term survival.Methods: We conducted a prospective study on cervical squamous cell carcinoma(SCC) patients diagnosed between January 2003 and December 2008. Cervical samples were tested for HPV viral load by the Hybrid Capture II(HCII) assay before treatment and 6 months after treatment. Clinical characteristics and follow-up information were also collected. A multivariable Cox proportional hazards model was used to adjust covariates in both the radical hysterectomy(RH) treatment group and concurrent chemoradiotherapy(CCRT) treatment group to identify relevant covariates, and then nomograms were constructed and used for internal validation.Results: A total of 520 SCC patients enrolled in this study with a median follow-up of 127 months, 360 patients received RH, whereas 160 patients received CCRT. The median HPV viral load in RH and CCRT groups was356.10 and 294.29, respectively. Tumor size was positively correlated with high pretreatment HPV load in both groups. In CCRT group, the advanced International Federation of Gynecology and Obstetrics(FIGO) stage and enlarged retroperitoneal lymph node status determined by computed tomography(LNSCT) were correlated with low HPV load group. Initial HPV viral load, FIGO stage and lymph node metastasis were prognostic factors for RH group, whereas HPV viral load, squamous cell carcinoma antigen(SCC-Ag) level and LNSCT were identified as prognostic factors for CCRT group. Nomograms incorporating these predictors for 10-year progression-free survival(PFS) were constructed [concordance index(C-index): 0.756, 0.749].Conclusions: A low pretreatment HPV viral load is an independent prognostic factor for poor prognosis of cervical SCC and is related to other clinicopathological factors. The survival nomogram based on HPV viral load could predict the long-term prognosis.

Endu combined with concurrent chemotherapy and radiotherapy for stage IIB-IVA cervical squamous cell carcinoma patients

BACKGROUND In recent years,the incidence of cervical cancer has increased with increasing life pressures and changes in women's social roles,posing a serious threat to women's physical and mental health.AIM To explore the clinical effect of Endo combined with concurrent radiotherapy and chemotherapy in the treatment of advanced cervical squamous cell carcinoma.METHODS A total of 120 patients admitted to the oncology department of our hospital were selected as the research subjects.They were equally divided into the test group and the control group(60 patients each)with a random number table.The test group was treated with Endo combined with concurrent radiotherapy and chemotherapy,and the control group was treated with concurrent radiotherapy and chemotherapy.We compared the serum thymidine kinase 1(TK1),human epididymis protein 4(HE4),vascular endothelial growth factor(VEGF),and squamous cell carcinoma-associated antigen(SCC-Ag)levels,the clinical effects and survival before and after radiotherapy and chemotherapy,the quality score,and the 3-year follow-up outcomes between the two groups.RESULTS After chemotherapy,the complete remission+partial remission rate was 85.00%in the test group and 68.33%in the control group;the difference was not statistically significant(P>0.05).Before chemotherapy,the serum TK1,HE4,VEGF,and SCC-Ag levels of the two groups were not significantly different(P>0.05).After chemotherapy,the levels of serum TK1(1.27±0.40 pmol/L),HE4(81.4±24.0 pmol/L),VEGF(235.1±38.0 pg/mL),and SCC-Ag(1.76±0.55 ng/mL)were lower than those in the control group[TK1(1.58±0.51 pmol/L),HE4(98.0±28.6)pmol/L,VEGF(284.2±54.1 pg/mL),and SCC-Ag(2.34±0.78 ng/mL)].The difference was statistically significant(P<0.05).Before chemotherapy,there were no significant differences in the physical,role,mood,cognition,social and symptom scale scores of the two groups(P>0.05).After chemotherapy,the physical,role,mood,cognitive and social scores were higher in the test group than in the control group,and the difference was statistically significant(P<0.05).The symptom scale scores of the test group were all lower than those of the control group,and the difference was statistically significant(P<0.05).The 3-year progression-free survival(PFS)rate was 43.33%in the test group and 26.67%in the control group;the overall survival(OS)rate was 48.33%in the test group and 33.33%in the control group;the differences were not statistically significant(P>0.05).The 3-year PFS time of the test group was 20.0 mo,which was longer than that of the control group(15.0 mo),and the difference was significant(P<0.05).The OS time of the test group was 30.0 mo,which was longer than that of the control group(18.0 mo),and the difference was significant(P<0.05).CONCLUSION Endo combined with concurrent radiotherapy and chemotherapy for the treatment of advanced cervical squamous cell carcinoma has a positive effect on reducing the level of tumor markers in patients,prolonging the PFS and OS times of patients,and improving the quality of life.

Expression of CDC42 in cervical squamous cell carcinoma and its correlation with clinicopathologic characteristics

Objective： The high expression of cell division cycle 42 protein （CDC42） may be involved in the occurrence and progression of several tumors. However, the expression and function of CDC42 in cervical squamous cell carcinoma remains unclear. This study aimed to investigate the expression of CDC42 in cervical squamous cell carcinoma and its correlation with clinicopathologic characteristics. Methods： The expression of CDC42 in 162 cervical squamous cell carcinoma tissue samples and 33 normal cervical tissue samples was investigated by immunohistochemistry. The CDC42 mRNA expression was detected by reverse transcription-polymerase chain reaction （RT-PCR）. Results： The cervical squamous cell carcinoma group showed a significantly higher CDC42 positive rate, compared to the normal cervical tissues （P〈0.05）. Fttrthermore, the tissues of stage Ⅱ-Ⅳ carcinoma patients showed higher CDC42 expression levels compared to stage I patients （P=0.05）. In addition, the expression of CDC42 was not correlated to age of patients, differentiation degree of cancer cells, or lymph node metastasis （P〉0.05）. Furthermore, compare with normal cervical tissues, the CDC42 mRNA expression in cervical cancer had no significant difference. Conclusions： CDC42 was up-regulated at protein level, but not mRNA level, in cervical squamous cell carcinoma. The high expression of CDC42 was correlated to the clinical stage of the patients, indicating that CDC42 might contribute to the progression of cervical squamous cell carcinoma.

Coexistence of cervical extramedullary plasmacytoma and squamous cell carcinoma:A case report

BACKGROUND Extramedullary plasmacytoma(EMP),a variant form of myeloma,is a rare solid plasma cell tumor that originates from the bone marrow hematopoietic tissue and accounts for about 3%of all plasma cell tumors.EMP can affect various tissues and organs,about 90%of which is found in the head and neck.However,EMP in the reproductive organs is rare,and is difficult to be distinguished from other primary or metastatic genital tumors according to clinical symptoms and imaging findings.CASE SUMMARY Herein,we report a case with coexistence of EMP and squamous cell carcinoma in the cervix.The first histopathological report of neoplasms on the surface of the cervix and vagina showed an EMP.Both ultrasound and pelvic enhanced magnetic resonance imaging(MRI)indicated that there was a tumor in the cervix.Thus,another cervical biopsy and pathological examination were performed,which indicated EMP combined with squamous cell carcinoma.Then,the patient underwent extensive total hysterectomy(type C1)+systemic lymph node dissection and received 25 external pelvic irradiations with a dose of 50 Gy following surgery.During 2-year follow-up,no recurrence was reported.CONCLUSION In conclusion,EMP involving the reproductive system is relatively rare.In this case,MRI,B-ultrasound,and cervical canal scraping were used to further determine the diagnosis of EMP combined with squamous cell carcinoma.The patient had improved prognosis after appropriate treatments.

Squamous cell carcinoma metastatic to cervical lymph nodes from unknown primary origin:the impact of chemoradiotherapy

The management of cervical lymph node metastases of squamous cell carcinoma from an unknown primary site is still a therapeutic challenge.We report here our experience in treating these patients with chemoradiotherapy as a curative approach.Data from 40 patients were reviewed.In total,20(50%) patients underwent excisional biopsy.All patients underwent radiotherapy,which was delivered to both sides of the neck and pharyngeal mucosa(extensive field),and concurrent chemotherapy consisting of weekly cisplatin at a dose of 40 mg/m2.The clinical stage of the cervical nodes at presentation was N1 in 25%,N2 in 60%,and N3 in 15%.Most patients(75%) developed at least grade 3 mucositis.Eight patients(20%) had grade 3 xerostomia and 18 patients(45%) required esophageal dilation for stricture.The 5-year overall survival(OS) rate of all patients was 67.5%.The 5-year OS rates of patients with N1,N2,and N3 lesions were 100%,67%,and 41%,respectively(P = 0.046).The 5-year progression-free survival rate was 62.5%.In multivariate analysis,only N stage significantly affected OS(P = 0.022).Emergence of the occult primary was very limited(1 patient only).Our results suggest that extensive irradiation of both sides of the neck and pharyngeal mucosa with concurrent chemotherapy results in a lower emergence of primary tumor.Because the survival of patients with unknown primary is comparable to that of patients with known primary,an attempt at cure should always be made.

THE OVEREXPRESSION AND SIGNIFICANCE OF CYCLIN D1 AND P53 IN CERVICAL SQUAMOUS CELL CARCINOMAS

Objective To investigate the significance of overexpresson of cyclin D1 and P53 protein in cervical squamous cell carcinomas.Methods Fifty cases of invasive cervical squamous cell carcinomas and 10 cases of normal cervical squamous epithelia were investigated with immunihistochemical technique. Results The overexpression of cyclin D1 and P53 in invasive cervical carcinomas was 70% and 50%, respectively. There was no overexpression of them in the control group. The overexpression of cyclin D1 in grade Ⅱ and Ⅲ was much higher than that in gradeⅠ(P<0.05). The overexpresson of cyclin D1 in stage Ⅲ of cervical carcinoma was significantly higher than that in stage Ⅱ (P<0.05). The overexpression of P53 in grade Ⅱ and grade Ⅲ of cervical carcinoma was remarkably higher than that in grade Ⅰ (P<0.05).Conclusion The action point of both cyclin D1 and P53 may be at G1/S transition. The overexpression of them was associated with development and progression of cervical carcinoma probably in different mechanisms and different pathways.

Chromosome analysis of esophageal squamous cell carcinoma cell line KYSE 410-4 by repetitive multicolor fluorescence in situ hybridization

Chromosome aberrations are distinctive features of human malignant tumors. Analysis of chromosomal changes can illuminate the molecular mechanisms underlying the development and progression of cancer. To establish the technique of multicolor fluorescence in situ hybridization （M-FISH） for identifying chromosome aberrations in esophageal carcinoma cell line KYSE 410-4, four pools of 6-color whole-chromosome painting probes have been designed and hybridized on the same metaphase spread by four rounds of repetitive FISH. Repetitive 6-color M-FISH was successfully established and the cytogenetic abnormalities in KYSE 410-4 cells were characterized. Chromosome gains occurred at 2q, 3, 8, 17p, and X. An isochromosome 3q was visualized in the cell line, which might be one intermediate mechanism leading to 3p losses and/or 3q gains. Furthermore, 16 structural arrangements were detected, including four derivative chromosomes. The rearrangement of the centromeric regions accounted for approximately 44% of all rearrangements. The results added a more complete and accurate information of the genetic alterations to the classical cytogenetic description of KYSE 410-4 and provided a detailed cytogenetic background data for appropriate use of the cell line. The established 6-color M-FISH was useful for analyzing chromosomes in the whole genome of human tumors.

MiR-25-3p attenuates the proliferation of tongue squamous cell carcinoma cell line Tca8113

Objective:To investigate the effects of miR-25-3p on the occurrence,development and proliferation of tongue squamous cell carcinoma cells.Methods:To establish tongue squamous cell carcinoma cell line Tca8113 that stably and highly express miR-25-3p using recombinant reiroviral vector-mediated gene transfer method.The proliferation of transfected Tca8113 was detected by thiazolyl blue tetrazolium bromide(MTT)and cell colony formation assays.eyclnD1,p21^(cipt)and p27^(kipt)mRNA expressions in the transfected Tca-8113 were detected by quantitative PCR.cyclinD1,p21^(cipt),p27^(kipt),AKT,p-AKT,FOXOt and p-FOX01 expressions in the transfected Tca8113 were detected by western blot analysis.In addition,miR-25-3p expression in the tongue squamous cell carcinoma cell line and tissue specimen was also detected by quantitative PCR.Results:Quantitative PCR showed that mitt-25-3p expression in the tongue squamous cell carcinoma cell lines and tissue specimen was significantly lower than that in the adjacent tissue.MTT and cell colony formation assays showed that after miR-25-3p overexpression,the proliferation of transfected Tca8113 was obviously attenuated.Western blot analysis and quantitative PCR showed that after miR-25-3p overexpression.p21^(cipt)and p27^(kipt)expressions were upregulated,while cyclinD1,AKT,FOXO1 expressions were downregulated,and AKT and FOXO1 phosphorylation was inactivated in the transfected Tca8113 cells.Conclusions:MiR-25-3p inhibited the proliferation of tongue squamous cell carcinoma cells and regulated cell cycle-related protein expression,playing an important role in the occurrence and development of squamous cell carcinoma of the tongue.

Detection of D2-40 monoclonal antibody-labeled lymphatic vessel invasion in esophageal squamous cell carcinoma and its clinicopathologic significance

Objective： This study aims to investigate the clinicopathologic significance of lymphatic vessel invasion （LVI） labeled by D2-40 monoclonal antibody in esophageal squamous cell carcinoma （ESCC）. Methods： Immunohistochemical assay was used to detect the expression of D2-40 and LVI in 107 ESCC patients. Then, the correlation between the clinicopathologic feature and the overall survival time of the patients was analyzed. Results： The lymph node metastasis rates were 70% and 21% in the LVI-positive and LVI-negative groups, respectively. The nodal metastasis rate was higher in the LVI-positive group than in the LVI-negative group. Multivariate regression analysis showed that LVI was related to nodal metastasis （P〈0.001）. The median survival time of the patients was 26 and 43 months in the LVI-positive and LVI-negative groups, respectively. Mthough univariate regression analysis showed significant difference between the two groups （P=0.014）, multivariate regression analysis revealed that LVI was not an independent prognostic factor for overall survival in the ESCC patients （P=0.062）. Lymphatic node metastasis （P=0.031）, clinical stage （P=0.019）, and residual tumor （P=0.026） were the independent prognostic factors. Conclusion： LVI labeled by D2-40 monoclonal antibody is a risk factor predictive of lymph node metastasis in ESCC patients.

N-linked glycoproteomic profiling in esophageal squamous cell carcinoma

BACKGROUND Mass spectrometry-based proteomics and glycomics reveal post-translational modifications providing significant biological insights beyond the scope of genomic sequencing.AIM To characterize the N-linked glycoproteomic profile in esophageal squamous cell carcinoma(ESCC)via two complementary approaches.METHODS Using tandem multilectin affinity chromatography for enrichment of N-linked glycoproteins,we performed N-linked glycoproteomic profiling in ESCC tissues by two-dimensional gel electrophoresis(2-DE)-based and isobaric tags for relative and absolute quantification(iTRAQ)labeling-based mass spectrometry quantitation in parallel,followed by validation of candidate glycoprotein biomarkers by Western blot.RESULTS 2-DE-based and iTRAQ labeling-based quantitation identified 24 and 402 differentially expressed N-linked glycoproteins,respectively,with 15 in common,demonstrating the outperformance of iTRAQ labeling-based quantitation over 2-DE and complementarity of these two approaches.Proteomaps showed the distinct compositions of functional categories between proteins and glycoproteins with differential expression associated with ESCC.Western blot analysis validated the up-regulation of total procathepsin D and high-mannose procathepsin D,and the downregulation of total haptoglobin,high-mannose clusterin,and GlcNAc/sialic acid-containing fraction of 14-3-3ζ in ESCC tissues.The serum levels of glycosylated fractions of clusterin,prolinearginine-rich end leucine-rich repeat protein,and haptoglobin in patients with ESCC were remarkably higher than those in healthy controls.CONCLUSION Our study provides insights into the aberrant N-linked glycoproteome associated with ESCC,which will be a valuable resource for future investigations.

Expression and clinical significance of Klotho and Beclin1 in cervical squamous carcinoma

Objective:To detect the expression of klotho and beclin1 protein in chronic cervicitis, low grade squamous intraepithelial lesion (LSIL) group, high grade squamous intraepithelial lesion (HSIL) group and cervical squamous cell carcinoma (SCC) group.Methods:Immunohistochemical technique (Envision) was used to detect the expression of Klotho and Beclin1 proteins in each study group. The correlation between the expression of the above two proteins and the pathological features of SCC and the expression of the two proteins in SCC were analyzed.Results: The positive expression rates of Klotho protein in chronic cervicitis group, LSIL group, HSIL group and SCC group were 95%, 92.86%, 65.38%, 27.90%, respectively. The positive rates of Beclin1 protein in chronic cervicitis group, LSIL group, HSIL group were 25.0%, 28.57%, 38.46% and 74.42%, respectively. The differences were statistically significant. The expression of Klotho and Beclin1 in SCC was correlated with the degree of tumor differentiation, but not with the age, figo stage, lymph node metastasis, tumor size, depth of invasion and vessel invasion, but not with the age of the patient, tumor figo stage, lymph node metastasis, tumor size, depth of invasion and vessel invasion. There was no correlation between the expression of klotho and beclin1 in SCC tissues.Conclusion: The abnormal expression of klotho and beclin1 may be related to the development, invasion and metastasis of cervical squamous cell carcinoma.

Relationship between Cell Proliferation and Apoptosis in Cervical Carcinoma

Objective To study the relationship between cell proliferation and apoptosis in cervical carcinoma and its clinical significance. Methods The cell proliferation and apoptosis of cervical epithelial cells in archival formalin-fixed, paraffin-embedded tissue sections of normal cervix, cervical intraepithelial neoplasms (GIN) and cervical squamous carcinoma were tested by using immunohistochemistry assay and DNA nick end-labeling technigue. The proliferation index (PI) and apoptosis index (AI) were calculated and their correlation with clinical and pathological data was analyzed.Results PI was gradually increased, but the AI and AI/PI ratio decreased from normal cervical epithelium, GIN to cervical carcinoma. There was no significant relationship among cell proliferation, apoptosis, clinical stages and pathological grades. High AI was always associated with a poor prognosis of the patients.Conclusion Cell proliferation and apoptosis allow to distinguish among normal epithelium, GIN and cervical carcinoma and are useful for the assessment of the malignant potential of tumor tissues.

Knockdown of lncRNAXLOC＿001659 inhibits proliferation and invasion of esophageal squamous cell carcinoma cells

BACKGROUND Studies have shown that long non-coding RNAs(lncRNAs)play a key role in almost all key physiological and pathological processes,including different types of malignant tumors.Our previous lncRNA microarray results have shown that lncRNA XLOC_001659 is upregulated in esophageal cancer(EC)tissues,with a fold change of 20.9 relative to normal esophageal tissues.But its effect and the molecular biological mechanisms on proliferation and invasion of EC cells remain unclear.AIM To investigate the effect of lncRNA XLOC_001659 on esophageal squamous cell carcinoma(ESCC)cells and explore the molecular biological mechanisms involved.METHODS RT-qPCR assay was used to quantify the expression levels of lncRNAXLOC-001659 and miR-490-5p.The proliferative capacity of the cells was determined using CCK8 and colony formation assays,and the effect of lncRNAXLOC-001659 on the invasion of ESCC cells was determined by Transwell assay.Dualluciferase reporter assay was used to detect the target genes of lncRNAXLOC-001659 and miR-490-5p.RESULTS The results of RT-qPCR showed that the expression of lncRNAXLOC_001659 was upregulated in ESCC cells.CCK-8 assay showed that knockdown of lncRNAXLOC_001659 significantly inhibited ESCC cell proliferation.Colony formation and Transwell invasion assays showed that knockdown of lncRNAXLOC_001659 or overexpression of miR-490-5p significantly inhibited ESCC cell growth and invasion.Furthermore,lncRNAXLOC_001659 acts as an endogenous sponge by competitively binding to miR-490-5p to downregulate miR-490-5p.Further results confirmed that miR-490-5p targeted PIK3CA,and the recovery of PIK3CA rescued lncRNAXLOC_001659 knockdown or miR-490-5p overexpression-mediated inhibition of cell proliferation and invasion,which suggested the presence of an lncRNAXLOC_001659/miR-490-5p/PIK3CA regulatory axis.CONCLUSION Knockdown of lncRNA XLOC_001659 inhibits proliferation and invasion of ESCC cells via regulation of miR-490-5p/PIK3CA,suggesting that it may play a role in ESCC tumorigenesis and progression.

Endometrial squamous cell carcinoma originating from the cervix: A case report

BACKGROUND Cervical squamous cell carcinoma(SCC)is the most common type of cervical carcinoma and is generally derived from a precancerous stage called cervical high-grade squamous intraepithelial lesion(HSIL).Usually,the cancer metastasizes through lymphatic or hematogenous dissemination,but rarely spreads upward into the uterus.Here,we report a case of cervical HSIL extending into the endometrium and finally progressing to SCC in the uterine cavity.CASE SUMMARY A 57-year-old postmenopausal woman visited our department and requested a routine cervical check-up.Four years ago,she had undergone a cervical loop electrosurgical excision procedure because of HSIL found during the gynecological examination,and she had not been checked again since.This time,a relapse of the cervical HSIL was diagnosed along with uterine pyometra and endometrial polyps.After 2 wk of antibiotic treatment,a laparoscopic hysterectomy was performed,and the final pathological examination revealed that the cervical HSIL had spread directly upward into the uterine cavity,gradually developing into cervical SCC in the endometrium.CONCLUSION Cervical HSIL/SCC can directly spread upward into the uterus with the most common symptoms of pyometra and cervical stenosis.More attention should be given to the early detection and prevention of this disease.

Arp2/3 Complex Is Expressed in Oral Squamous Cell Carcinoma: An Immunohistochemical Study of 88 Cases

Background: We investigated the immunohistochemical expression of Arp2/3 complex in 88 oral squamous cell carcinomas (OSCCs) and correlated it with the tumor type and grade. Materials and methods: This is a retrospective study of 88 cases of OSCCs (9 verrucous carcinomas, 4 carcinomas in situ, 37 well differentiated OSCCs, 32 moderately differentiated OSCCs, and 6 poorly differentiated OSCCs), stained with mouse monoclonal antibodies for Arp2 and Arp3. Staining was graded according to the extent of positivity by two observers. Results: Arp2 positivity was seen in 79 (89.77%) cases and Arp3 positivity in 78 (88.63%) cases. In positive cases, Arp2 expression was graded as (+) in 12.5%, (++) in 28.4% and (+++) in 48.86% of the cases;Arp3 was graded as (+) in 36.36%, (++) in 30.68% and (+++) in 21.59% of the cases. Conclusion: Expression of Arp2 and Arp3, indicative of the formation of the Arp2/3 complex, was seen in most OSCCs examined. Although no statistically significant correlation was found between the immunohistochemical expression of Arp2/Arp3 and tumor type or grade, the more common expression in invasive OSCCs than in non-invasive verrucous carcinomas and carcinomas in situ is indicative of its involvement in the biological behaviour of the lesions. The availability of Arp2/3 inhibitors that could be used in clinical practice warrants further study of the expression of Arp2/3 in OSCC.

宫颈癌患者血清SCC-Ag、NLR水平与临床病理特征及预后关系

目的:探讨宫颈癌患者血清鳞状细胞癌抗原(SCC-Ag)、中性粒细胞与淋巴细胞比值(NLR)与临床病理特征及预后关系。方法:纳入2018年1月-2023年1月本院收治的108例宫颈癌患者为宫颈癌组,宫颈上皮内瘤病变(CIN)患者108例为CIN组,健康体检健康女性108例为对照组。比较3组血清SCC-Ag、NLR水平,分析宫颈癌组血清SCC-Ag、NLR水平与临床病理特征及与预后关系。结果:血清SCC-Ag、NLR水平,宫颈癌组(7.35±1.76、4.65±1.06)、CIN组(2.06±0.53、3.41±0.89)、对照组(0.54±0.12、1.53±0.34)依次降低(P<0.05)。宫颈癌患者血清SCC-Ag、NLR水平与病理类型、FIGO分期、病理分级、肌层浸润深度和盆腔淋巴结转移有关(P<0.05)。Kaplan-Meier显示,SCC-Ag、NLR高表达组总生存率、无病生存率均低于SCC-Ag、NLR低表达组,SCC-Ag高表达+NLR高表达组总生存率、无病生存率最低(均P<0.05)。结论:宫颈癌患者血清SCC-Ag、NLR水平与病理类型、FIGO分期、病理分级和肌层浸润深度等有关,且SCC-Ag、NLR水平越高患者预后越差。

宫颈癌患者血清微小RNA-195、双皮质素样激酶1、鳞状细胞癌抗原表达水平与临床病理特征及预后相关性研究

目的:探讨宫颈癌患者血清微小RNA-195(miR-195)、双皮质素样激酶1(DCLK1)、鳞状细胞癌抗原(SCC-Ag)水平与临床病理特征及预后的相关性。方法:选取宫颈癌患者72例为观察组,同期体检健康女性60例为对照组,比较两组血清miR-195、DCLK1、SCC-Ag表达水平。采用Spearman法分析宫颈癌患者血清miR-195、DCLK1、SCC-Ag与临床病理特征的相关性,随访3年,记录患者生存情况。采用Cox回归模型分析宫颈癌患者预后的影响因素。结果:观察组血清DCLK1、SCC-Ag水平较对照组升高,miR-195水平较对照组下降(均P<0.05)。血清miR-195水平与淋巴结转移、国际妇产科联盟(FIGO)分期、肿瘤分化程度呈负相关,DCLK1水平与FIGO分期、肿瘤分化程度呈正相关,SCC-Ag水平与肿瘤分化程度、肿瘤直径呈正相关(均P<0.05)。miR-195高表达患者3年生存率高于低表达患者,DCLK1、SCC-Ag高表达患者3年生存率低于低表达患者(均P<0.05)。FIGO分期、分化程度、淋巴结转移、肿瘤直径及血清miR-195、DCLK1、SCC-Ag水平是宫颈癌患者预后的独立影响因素(均P<0.05)。结论:宫颈癌患者血清DCLK1、SCC-Ag水平升高,miR-195水平降低,三者与临床病理特征和预后有关,是宫颈癌患者预后的独立影响因素。

Expressions of Toll-like receptors 3,4,7,and 9 in cervical lesions and their correlation with HPV16 infection in Uighur women

Recent findings show that Toll-like receptors(TLRs) expressed in immune cells play a crucial role in the innate immune response and the subsequent induction of adaptive immune responses against microbial infection on tissue injury.Furthermore,expression of TLRs in cancer cells is associated with tumor proliferation and invasion.To explore the role of TLRs expression in cervical carcinogenesis in Uighur women,we detected the expressions of TLR3,TLR4,TLR7,and TLR9 in 25 normal cervical tissues,64 cervical intraepithelial neoplasia(CIN) tissues,and 63 cervical squamous cell carcinoma(CSCC) tissues using immunohistochemical staining,as well as human papillomavirus type 16(HPV16) infection using PCR.All samples used in this study were from Xinjiang Uighur women.We found the expression levels of TLR4,TLR7,and TLR9 were significantly higher in CIN and CSCC than in normal controls(P < 0.05).Up-regulation of TLR4 and TLR7 were correlated with tumor differentiation but not FIGO stage or lymph node metastasis(P > 0.05).Up-regulation of TLR9 was correlated with lymph node metastasis(P < 0.05) but not tumor differentiation or FIGO stage(P > 0.05).We also analyzed the correlation between the expressions of TLRs and HPV16 infection and found that the expressions of TLR4 and TLR9 significantly correlated with HPV16 infection in CIN(r = 7.434,P = 0.006;r = 7.123,P = 0.008) and CSCC(r = 6.423,P = 0.001;r = 8.478,P = 0.004),whereas the expression of TLR3 was not significantly different in any of the three groups and had no significant correlation with HPV16 infection.Our results suggest that high expression of TLR4,TLR7,and TLR9 may play important roles in the development and progression of CIN and CSCC in Uighur women,and the expressions of TLR4 and TLR9 can be up-regulated by HPV16 infection.