Background:Emerging mounts of research support the ancestral theory of cancer, indicating that tumorigenesis and embryogenesis share many similar biological features, yet yield distinct outcomes. Gene co-expression networks underlie both embryonic development and tumorigenesis. We hypothesize that deviations in the gene interaction patterns in tumors compared to villi predispose to malignancy and worse prognosis. Methods:By constructing a gene co-expression network of villi and colorectal cancer (CRC) and conducting functional enrichment analysis to identify "off-track genes." Cox regression assessed prognostic significance, while tissue microarrays evaluated protein expression and progression. Additionally, mRNA sequencing of chondroitin polymerizing factor (CHPF)-knockdown LOVO and SW480 cell lines was conducted and validated via in vitro assays. Results:We found that genes in villi and CRC have similar functions, but the genes that performed corresponding functions were not identical. Then, according to "off-track theory" and linear regression models, we obtained 24 genes whose aberrant expression was significantly associated with poor CRC survival. Notably, CHPF emerged as an adverse prognostic factor. Immunohistochemical analysis confirmed that CHPF is an independent prognostic marker for CRC. Furthermore, cell phenotype assays demonstrated that CHPF enhances proliferation and migration, suppresses apoptosis, and engages in the TNF signaling pathway. Conclusion:These findings validate that villi development can serve as a research model for tumorigenesis, and identify CHPF is an independent oncogenic factor in CRC, suggesting its potential as a prognostic biomarker and a therapeutic target for clinical treatment.

Background:Since the approval of immune checkpoint inhibitors (ICIs) in extensive-stage small-cell lung cancer (ES-SCLC) patients, immunotherapy has been commonly prescribed in first-line and sometimes in subsequent-line treatment in clinical practice. However, real-world data on ICIs in ES-SCLC remain limited. Objectives:To delineate the current therapeutic landscape of ES-SCLC and assess the efficacy and outcomes of immunotherapy in different clinical settings. Design and methods:Patients with ES-SCLC who received at least two lines of therapy from February 2020 to February 2024 were retrospectively recruited. All enrolled subjects were divided into two groups, namely "ICIs cohort" and "chemotherapy-only cohort" according to the treatment regimens they received in the entire disease course. Patients in the ICIs cohort who received immunotherapy as first-line treatment were analyzed separately from those who received it in later lines. Survival analysis was conducted to evaluate the clinical significance of ICIs in different treatment settings using the Kaplan-Meier method. The utility of thoracic radiotherapy was also evaluated in ES-SCLC patients. Multivariate Cox regression was applied to identify independent predictors of survival in ES-SCLC. Results:A total of 214 patients were enrolled during the timeframe, of whom 81 received ICIs in first-line treatment and 78 received ICIs in subsequent-line treatment. In survival analysis, the ICIs cohort demonstrated significantly longer overall survival (OS) than the chemotherapy-only cohort, both in the first-line (17.0 vs 14.27 months; p = 0.045) and subsequent-line settings (16.87 vs 14.27 months; p = 0.017). In addition, the median OS was significantly prolonged in patients who underwent local thoracic radiotherapy compared to those who did not (20.53 vs 14.63 months; p = 0.005). Multivariate survival analysis validated that liver metastasis independently predicts inferior survival (p < 0.001). Meanwhile, immunotherapy administration (p = 0.002) and thoracic radiotherapy (p = 0.036) emerged as significant independent prognostic factors for prolonged survival in ES-SCLC patients. Conclusion:The incorporation of immunotherapy, either in first-line or subsequent-line treatment, significantly improved survival outcomes in ES-SCLC. Notably, local thoracic radiotherapy retained its significant survival benefit in ES-SCLC in the immunotherapy era.

Septic acute lung injury (ALI) is a common complication of sepsis with high morbidity and mortality but lacks specific treatment. This study aimed to elucidate the role of circular RNA TLK1 (circTLK1) in neonatal septic ALI.Murine cecal slurry was used to induce neonatal sepsis-induced ALI model in vivo. Hematoxylin and eosin staining was performed to detect the pathological changes in lung tissues. Pulmonary microvascular endothelial cells were treated with lipopolysaccharide (LPS) to induce neonatal sepsis-induced ALI model in vitro. The levels of IL-1β and IL-6 were detected by enzyme-linked immunosorbent assay. A lactate dehydrogenase (LDH) detection kit was used to detect LDH activity. Cell Counting Kit-8 assay and flow cytometry detected cell viability and apoptosis. The genes' expression was measured by quantitative real-time reverse-transcription polymerase chain reaction and western blot. The relationship between circTLK1 and Elavl1 or Elavl1 and Nox4 was detected using RNA immunoprecipitation assay.Our results illustrated that circTLK1 was highly expressed in neonatal sepsis-induced ALI model, and circTLK1 knockdown alleviated cell inflammation and apoptosis in neonatal sepsis-induced ALI model. Similarly, we found that circTLK1 knockdown alleviated neonatal sepsis-induced ALI. Mechanically, circTLK1 mediated Elavl1 binding to Nox4 messenger RNA and increased its stability. Functionally, circTLK1 knockdown alleviated cell inflammation and apoptosis by regulating Nox4 in the neonatal sepsis-induced ALI model.CircTLK1 knockdown alleviated cell inflammation and apoptosis by the Elavl1/Nox4 axis in neonatal sepsis-induced ALI. Our research provided a novel direction for the treatment of neonatal sepsis-induced ALI. · CircTLK1 knockdown relieved neonatal septic ALI.. · CircTLK1 mediated Elavl1 binding to Nox4 mRNA..

e20615 Background: Combine chemotherapy and immunotherapy have become the first-line treatment program for extensive small cell lung cancer. The aim of this study is to explore the safety and efficacy of neoadjuvant chemotherapy and immunotherapy in limited-stage small cell lung cancer. Methods: Treatment-naïve patients were enrolled and the patients received the 2-3 cycles of neoadjuvent chemotherapy and atezolizumab (1200mg, D1). surgery was performed within 4-6 weeks after the last treatment. The primary endpoint was surgery patients pathological complete response (PCR). Safety was assessed by adverse events (AEs) and postoperative complications. This trial was registered at the Chinese Clinical Trial Registry (Registration Number: (ChiCTR2100042367). Results: Recruitment started in May 2020. We reported 9 patients with neoadjuvent immunochemotherapy who have completed surgical treatment. Baseline characteristics: 7 males, with an average age of 52.1 years old, all ECOG PS 0-1; 6 current smokers; clinical stages IIB / IIIA / IIIB n = 6 / 1 / 2. There were 1 atezolizumab treatment-related Gr1 AEs (rush) and 4 treatment-related Gr 3-4 AEs. According to Recist 1.1, all patients achieved partial response. 9 patients completed surgery, 3 patients received bilobectomy, and 3 patients underwent pneumonectomy. Surgical methods included robot-assisted thoracoscopic surgery (RATS) /video-assisted thoracoscopic surgery (VATS) (3, 33.3%) and thoracotomy (6, 66.7%). Complete resection (R0) was achieved in 100% of patients (9/9). The mean operation time was 136 min; the mean bleeding volume was 194.4ml, and the mean hospital stay was 8.9 days. The postoperative pathology results showed a PCR (66.7%) in 6 patients and a MPR (88.9%) in 8 patients. Conclusions: Neoadjuvant chemotherapy and atezolizumab therapy significantly improves PCR in small cell lung cancer without unknown AE events and no surgical delay, so this protocol is safe and feasible. Whether the survival benefit is still unknown. Keywords: neoadjuvant therapy, Small cell lung cancer, immunotherapy, surgery, PCR. Clinical trial information: ChiCTR2100042367. [Table: see text]

目的 了解子宫颈癌根治性子宫切除术后患者下尿路症状患病情况及其相关因素.方法 选择2012年1月至2015年3月在全国13家研究中心接受Piver Ⅲ型子宫切除的690例宫颈癌患者,并按照年龄和体质指数匹配妇科门诊无手术史良性疾病患者690例作为对照组,采用女性下尿路症状国际尿失禁标准问卷(ICIQ-FLUTS)和膀胱过度活动症评分(overactive bladder symptom score,OABSS)对两组患者进行问卷调查.结果 宫颈癌组下尿路症状患病率(78.3％,540/690)与对照组(78.7％,543/690)相似(P＞0.05).宫颈癌组储尿期症状患病率(66.2％,457/690)低于对照组(75.5％,521/690)(P＜0.05),而排尿期症状(52.3％,361/690)和膀胱过度活动症(overactive bladder symptom,OAB)(14.5％,100/690)患病率显著高于对照组(24.1％,166/690;8.8％,61/690)(P＜0.05).单因素分析显示,腹腔镜手术、术中切除宫旁长度或阴道长度＞3 cm与排尿期症状、OAB患病相关(P＜0.05).Logistic分析显示,腹腔镜手术是排尿期症状(OR=2.380,95％CI:1.664～3.405)和OAB的危险因素(OR=1.972,95％CI:1.155～3.367).结论 宫颈癌患者根治性子宫切除术后排尿期症状及OAB患病率升高,可能与切除较多的宫旁和阴道组织有关.

BackgroundVasovagal syncope (VVS) is common in children and significantly affects their quality of life. To our knowledge, this the first case report of SCN5A gene mutation associated with VVS and third-degree atrioventricular block (atrioventricular block, AVB), which could help pediatricians aware that VVS is not always a benign condition and help to identify VVS children at the risk of sudden death.Case presentationA twelve-year-old male child was admitted to Beijing Children's Hospital of Capital Medical University for chest tightness for 9days and syncope in July 2018. The child was diagnosed as VVS with third-degree AVB after complete investagations. A heterozygous mutation in the exon coding region of the SCN5A gene, C. 5851G>T (coding region 5551 nucleotide changed from G to T), was detected in the peripheral blood of the child. Electrophysiological examination and modified vagal ganglion radiofrequency ablation were performed in the child. The ECG playback was normal on the second day after operation. Holter showed no abnormality and no chest tightness or syncope occurred after 3months and 1 year follow-up.ConclusionsOur case report firstly reported that SCN5A mutation contributed to the pathogenesis of VVS with third-degree AVB. Vagal ganglion modified ablation have obtained good therapeutic effect. Gene analysis was of great value to the accurate diagnosis and treatment of VVS children.

目的 探讨甲磺酸阿帕替尼联合表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitors,EGFR-TKIs)对经EGFR-TKIs治疗缓慢进展的晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的疗效和安全性.方法 选取2018年5月至2019年4月首都医科大学附属北京胸科医院收治的24例服用EGFR-TKIs出现缓慢进展的NSCLC患者,继续使用EGFR-TKIs同时联合甲磺酸阿帕替尼,每2个月复查1次,至疾病进展,对患者的近期疗效、毒性作用和不良反应进行分析.结果 排除入组时间晚尚未复查的1例外,其余23例中无完全缓解患者,部分缓解和疾病稳定者分别为7例和16例,无疾病进展患者.总缓解率和疾病控制率分别为30.4％和100.0％.结论 阿帕替尼联合EGFR-TKIs治疗EGFR敏感突变的晚期NSCLC临床效果可靠,毒性作用和不良反应可耐受.

Lung adenocarcinoma (LUAD) is a common type of lung cancer with high incidence and poor prognosis. Hypoxia and DNA methylation play important regulatory roles in cancer progression. The purpose of the present study was to explore the relationship between hypoxia and DNA methylation, and to identify key genes for hypoxia-regulated LUAD progression. Hypoxia score (HS) was calculated using the GSVA algorithm. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction (PPI) analysis were performed using clusterProfile package, STRING database and Cytoscape software. Kaplan-Meier curves of overall survival (OS) and disease-free survival (DFS) were drawn using R software. Smoking status and cancer stages were significantly associated with LUAD hypoxia, and hypoxia is a poor prognostic factor for LUAD. Compared with HS-low group, 1803 aberrantly methylated DEGs were identified in HS-high group. KEGG analysis showed that the 1803 genes were enriched in the metabolic pathways associated with hypoxia stress, angiogenesis and cancer progression. FAM20C, MYLIP and COL7A1 were identified as the hypoxia-related key genes in LUAD progression, which were regulated by DNA methylation. Hypoxia in LUAD tumor cells led to changes in DNA methylation patterns. In-depth study of the relationship between hypoxia and DNA methylation is helpful to elucidate the mechanism of tumorigenesis, and provides new ideas for LUAD treatment.

目的:分析非小细胞肺癌患者中表皮生长因子受体(EGFR)突变为包含少见突变的复合突变患者的临床特征与治疗效果,为EGFR复合少见突变阳性的非小细胞肺癌患者的治疗提供依据.方法:回顾性分析22例EGFR复合少见突变阳性的非小细胞肺癌患者的病历资料及治疗经过.比较患者EGFR基因突变类型、临床资料特征及治疗效果.结果:在我院2014年-2018年病理科检测的EGFR突变阳性的3224名患者当中,EGFR复合突变共147例,占比为4.56％,而复合少见突变患者共27例,占比0.84％.晚期复合少见突变患者中有11名使用EGFR酪氨酸激酶抑制剂(TKI)治疗,对这些患者的治疗用药及疗效分析后,使用一代TKI治疗患者6人,中位无进展生存时间(PFS)为8.4个月,二代TKI治疗患者5人,中位PFS为7.2月,两组之间无明显统计学差别.结论:EGFR复合少见突变的患者使用一代或二代EGFR-TKI治疗疗效无明显差别.

BACKGROUND:Vasovagal syncope (VVS) accounts for 60-80% of cases of neurally mediated syncope. VVS results from acute orthostatic intolerance and recurrent syncopal attacks, which can seriously affect an individual's quality of life. In addition, some children even experience trauma during attacks. Therefore, it is particularly important to clarify the pathogenesis of VVS. The aim of our study is to reveal the latest research progress of VVS.DATA SOURCES:Literature that involved the pathogenesis of VVS were selected from Cochrane Library (1990-2019), EMBASE (1991-2019) and PubMed (1968-2019) databases.RESULTS:Hypovolemia, autonomic dysfunction, vasomotor dysfunction, baroreceptor reflex abnormalities, endothelial dysfunction, serotonin surges, and gut microbiota were involved in the underlying mechanism of VVS.CONCLUSIONS:VVS is not always a benign prognosis. Various aspects were involved in its pathogenesis. Bezold-Jarish reflex, dysfunction of the autonomic nervous system, genetic factors and so on played important roles in VVS; however, the mechanism remains unclear.

Dear Editor, The placenta separates fetus and mother,with the trophoblast playing a most important role in defense against potential harm from the maternal immune system.Although the placenta is normal tissue,it shares several common features with malignant cells.1 Based on similar strategies,these cells are able to successfully coexist in an immunologically hostile environment.2 A detailed analysis and comparison of different placental model systems will not only contribute to our in-depth understanding of the exciting field of placental development research but also may offer valuable insights on the broad field of cancer studies.

BACKGROUND:Mesenchymal-epithelial transition (MET) exon14 skipping mutations represent a clinically unique molecular subtype of NSCLC. The prevalence rates of MET exon 14 skipping in lung adenocarcinoma (ADC) range from 0.9% to 4.0% in Asian populations. Since some somatic variants that do not encompass the MET exon 14 splice sites might also induce MET exon 14 skipping, the RNA-based sequencing is speculated as the most accurate method for detecting exon 14 skipping.PATIENTS AND METHODS:A total of 951 NSCLC patients from two hospitals were enrolled in this study. MET exon14 skipping was detected using RNA-based next-generation sequencing (NGS). Also, immunohistochemistry (IHC) was performed in 405 samples simultaneously.RESULTS:The overall estimated prevalence of MET exon 14 skipping was approximately 1.8% in ADCs and 1.7% in NSCLCs. The detection rate of MET exon 14 skipping from surgical resection specimen was 2.3% in NSCLCs and 2.0% in ADCs. The MET exon 14 skipping was identified in 6.6% of EGFR/KRAS/ALK/ROS1/RET-negative ADCs. Additionally, PD-L1 was found to be highly expressed in NSCLC patients harboring MET exon 14 skipping (P<0.01).CONCLUSION:The prevalence of MET exon14 skipping in lung ADCs in the East Asian population was similar to that of the Western population as assessed by RNA-based NGS. The NSCLC patients with MET exon 14 skipping were older than those with other oncogenic driver mutations, such as EGFR, ALK, and ROS1. In addition, PD-L1 was highly expressed in NSCLC patients with MET exon 14 skipping.

OBJECTIVES:The molecular profiles and prognosis of anaplastic lymphoma kinase (ALK) fusion and resectable non-small cell lung cancer (NSCLC) remain unclear. This study aimed to explore the distribution of ALK fusion variants and prognostic factors in patients with surgically resected NSCLC.MATERIAL AND METHODS:Among the 93 ALK positive surgical patients screened by immunohistochemistry (IHC) or real-time polymerase chain reaction (RT-PCR), 63 patients were confirmed as ALK rearrangement by next-generation sequencing (NGS), including 55 cases of stage I-III and 8 cases of stage IV. Medical records were retrospectively reviewed, the distribution of ALK fusion variants and prognostic factors were analyzed.RESULTS:All of the 55 early stage patients were histological adenocarcinoma. No other fusion types were found except for echinoderm microtubule-associated protein-like 4- anaplastic lymphoma kinase (EML4-ALK). EML4-ALK variant 1 (E13:A20; 25/55, 45.5 %) was the predominant variant type, followed by EML4-ALK variant 3 (E6:A20; 19/55, 34.5 %) and variant 2 (E20:A20; 8/55, 14.5 %). Concomitant mutations occurred in 22 patients (22/55, 40.0 %), which involved in 32 co-mutations from 12 kinds of mutated genes. TP53 mutations were most common in coexisting mutations (13/32, 40.6 %). TP53 mutations were less frequently occurred in variant 1 group (3/25, 12.0 %) than in non-variant 1 group (10/30, 33.3 %, P = 0.064). The median disease-free survival (DFS) of the 55 patients was 22.1 months, and the median overall survival (OS) was not mature at the time of analysis. Multivariable analysis showed that stage T3 and EML4-ALK variant 3 were independent prognostic factors for shorter DFS. Neither TP53 mutations nor any coexisting mutations were related to prognosis.CONCLUSIONS:This study illustrated the patterns of EML4-ALK fusion variants and gene profiles in patients with resected NSCLC. Advanced T stage and EML4-ALK variant 3 were associated with worse prognosis. The role of TP53 mutations in prognosis is worthy of further study.

OBJECTIVE:To evaluate the efficacy of folate receptor-mediated tumor detection (FRD) for identifying high-grade intraepithelial squamous lesions (HSIL) in the triage of women who are positive for human papillomavirus (HPV), and those with cytology findings of atypical squamous cells of undetermined significance (ASCUS).METHOD:A secondary analysis of prospectively collected data from 1504 women who had abnormal results during primary cervical cancer screening at 13 hospitals in Beijing, China, between November 2014 and August 2015. The detection accuracy of FRD was evaluated among HPV-positive women and women with ASCUS referred for colposcopy examination.RESULTS:Among 1338 women with HPV, the percentage coincidence with pathology findings was higher for FRD (66.7%) than for cytology of ASCUS or higher (51.5%). The rate of colposcopy referral for cytology and FRD as a triage tool was 969 (72.4%) and 736 (55.0%), respectively. Thus, 233 (17.4%) fewer women would be referred for colposcopy by FRD. Among 476 women with cytology of ASCUS, the percentage coincidence with pathology findings was higher for FRD (63.4%) than for HPV (35.9%).CONCLUSION:FRD was found to be a promising triage tool for women who are HPV-positive and those with cytology findings of ASCUS.

Hypoxia and stemness are important factors in tumor progression. We aimed to explore the ncRNA classifier associated with hypoxia and stemness in lung adenocarcinoma (LUAD). We found that the prognosis of LUAD patients with high hypoxia and stemness index was worse than that of patients with low hypoxia and stemness index. RNA expression profiles of these two clusters were analyzed, and 6867 differentially expressed (DE) mRNAs were screened. Functional analysis showed that DE mRNAs were associated with cell cycle and DNA replication.Protein–protein interaction network analysis revealed 20 hub genes, among which CENPF, BUB1, BUB1B, KIF23 and TTK had significant influence on prognosis. In addition, 807 DE lncRNAs and 243 DE miRNAs were identified. CeRNA network analysis indicated that AC079160.1-miR-539-5p-CENPF may be an important regulatory axis that potentially regulates the progression of LUAD. The expression of AC079160.1 and CENPF were positively correlated with hypoxia and stemness index, while miR-539-5p expression level was negatively correlated with hypoxia and stemness index. Overall, we identified CENPF, BUB1, BUB1B, KIF23 and TTK as potentially key genes involved in regulating hypoxia-induced tumor cell stemness, and found that AC079160.1-miR-539-5p-CENPF axis may be involved in regulating hypoxia induced tumor cell stemness in LUAD.

Drug resistance severely limits the effectiveness of chemotherapeutic treatment in ovarian cancer. The present study aimed to investigate the role of long non-coding RNA LINC00152 (LINC00152) in the cisplatin resistance of ovarian cancer. The expression level of LINC00152 was significantly increased in the ovarian cancer CoC1 and CoC1/DDP cell lines compared with the normal ovarian IOSE-80 cell line. To further investigate the function of LINC00152, small interfering RNAs (siRNAs) targeting LINC00152 were transfected into COC1 and COC1/DDP cells, which were subsequently treated with varying concentrations of cisplatin. The results revealed that LINC00152 silencing increased the apoptotic rates and enhanced the chemosensitivity of CoC1 and CoC1/DDP cells to cisplatin. Furthermore, downregulation of LINC00152 significantly decreased Bcl-2, and increased Bax and cleaved caspase-3 expression levels. Additionally, LINC00152 silencing decreased the expression of multidrug resistance-associated gene 1 (MDR1), multidrug resistance-associated protein 1 (MRP1) and glutathione S-transferase π (GSTπ). Collectively, the data demonstrated that LINC00152 knockdown increased the chemosensitivity of epithelial ovarian cancer cells to cisplatin by increasing apoptosis and decreasing the expression levels of MDR1, MRP1 and GSTπ.

目的:探讨宫颈癌患者Ⅲ型子宫切除术后的盆底功能情况,分析其相关影响因素.方法:回顾性分析了实施子宫颈癌Ⅲ型子宫切除术的患者,共71例,按照手术时间将患者分为A组和B组,术后时间≤2年的为A组,术后时间>2年的为B组.收集患者一般资料,宫颈癌的治疗情况、术后情况,了解宫颈癌患者盆底功能情况、排尿功能改变、排便功能改变、性生活情况等.结果:两组排尿困扰量表得分、盆底功能障碍问卷总分、OABSS调查表得分比较,差异均有统计学意义(P<0.05).单因素分析显示,有、无盆底肌功能障碍的患者的年龄、BMI、妊娠次数、分娩次数、留置尿管时间、术后时间及术后放疗次数比较,差异均有统计学意义(P<0.05);多因素分析显示,患者BMI、分娩次数、留置尿管时间、术后时间及术后是否放疗是其独立危险因素(P<0.05).结论:术后时间>2年较术后时间≤2年的患者更易发生盆底功能障碍性疾病,患者的BMI过大、分娩次数过多、留置尿管时间长、术后时间的推移及术后放疗是盆底功能障碍性疾病发生的独立影响因素,可增加患者术后盆底功能障碍发生的风险.患者术后性生活频率及质量低下,且对宫颈癌疾病认识不足,也是应该引起关注的方面.

Objectives The aim of the study was to evaluate the performance of a folate receptor-mediated tumor detection (FRD) assay for detection of cervical high-grade lesions. Materials and Method A total of 1504 patients with abnormal cytology and/or positive human papillomavirus (HPV) testing during primary screening from November 2014 to August 2015 were enrolled. The patients were recruited from the Peking University People's Hospital and 12 other hospitals. Folate receptor-mediated tumor detection was applied in all the patients before colposcopy to compare the detection rate, sensitivity, specificity, positive predictive value, negative predictive value, and coincidence rate with HPV and cytology tests according to the pathologic diagnosis. Results In the total of 1504 patients, 503 patients were negative for intraepithelial lesion or malignancy, 440 patients were cervical intraepithelial neoplasia (CIN) 1, 254 patients were CIN 2, 257 patients were CIN 3, 46 patients were squamous cell carcinoma, and 4 patients were adenocarcinoma in situ. The sensitivity of FRD was 77.72%, which was less than cytology (80.39%) and HPV testing (95.54%). The specificity of FRD was 60.02%, which was greater than cytology (30.12%) and HPV testing (14.95%). The coincidence rate of FRD to the pathologic diagnosis (66.62%) was also significantly greater than atypical squamous cells of undetermined significance cytology and above (48.87%) and HPV testing (45.01%, p < .0001). The detection rate of FRD for all grades of lesions increased with the severity of lesions. Conclusions Folate receptor-mediated tumor detection has a slightly lower sensitivity and a higher specificity than cytology and HPV testing for detection of CIN 2+. Simplicity of FRD requires less professional skill. Folate receptor-mediated tumor detection could be a candidate test for cervical cancer screening especially in low- and middle-income countries. However, FRD still needs more clinical trial data to demonstrate its ability in general screening population.

The high rate of mortality associated with ovarian cancer (OC) is due in part to the development of resistance to chemotherapy, which allows the resistant tumour cells to invade and metastasise. Clarifying the mechanistic basis for drug resistance may reveal novel avenues for treatment. The present study investigated the mechanism of paclitaxel (PTX) resistance in human epithelial OC by evaluating the expression of stem cell-associated cell surface markers endoglin (CD105), CD44 antigen and vascular cell adhesion molecule 1 (CD106), in association with the malignant potential of the human OC OVCAR3 cell line and its PTX-resistant derivative OC3/TAX300. The expression of CD105, CD44 and CD106 was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and flow cytometry, and cell invasion was evaluated using a Transwell invasion assay. CD105, CD44 and CD106 levels were increased in OC3/TAX300 cells compared with the OVCAR3 cells, as determined by flow cytometry (P<0.01) and RT-qPCR (P<0.05). Additionally, the number of invading cells was increased in the OC3/TAX300 group compared with the OVCAR3 group (54.7±6.65 vs. 31.8±6.55; P<0.01). A western blot analysis of cell surface marker expression in 80 clinical epithelial OC tissue samples, differing in terms of sensitivity to drug treatments, disease stage and degree of differentiation, revealed that high CD105, CD44 or CD106 expression was associated with drug resistance, advanced disease stage, poor differentiation and high rate of recurrence. These data indicated that exposure to high doses of PTX enhanced the stem-like properties of OC cells, which are associated with drug resistance and invasion and lead to poor prognosis due to induced chemoresistance and/or metastasis. Therefore, CD105, CD44 and CD106 may serve as potential stem cell-associated cell surface and prognostic markers, and therapeutic targets, in OC.