Biomarker For Cervical Cancer Research Articles

Bifunctional Nanomaterial Enabled High-specific Isolation of Urinary Exosomes for Cervical Cancer Metabolomics Analysis and Biomarker Discovery

Cervical cancer (CC) remains a critical public health issue, highlighting the importance of early detection. However, current methods such as cytological and HPV testing face challenges of invasiveness and low patient compliance. Exosomes, emerging as crucial in cancer diagnosis, offer promise due to their noninvasive, highly specificity, and abundant biomarkers. However, isolating exosomes efficiently remains challenging. In this study, we designed and synthesized a bifunctional affinity nanomaterial Fe3O4 @CD63-CLIKKPF, based on the synergistic interaction between its modified aptamer CD63 and peptide CLIKKPF, and CD63 protein and PS of exosomes which can achieve high specificity and high yield separation of urinary exosomes. Notably, the co-modified aptamer CD63 and peptide CLIKKPF not only enable efficient exosome isolation by leveraging dual-affinity mechanisms through a synergistic "AND" logic analysis, but also could be achieved on the Fe3O4 in one-step reaction at room temperature via Fe-S bonding. Combined with LC-MS/MS, we conducted exosome metabolomics analysis in healthy individuals and CC patients across various stages, and machine learning models demonstrated accurate classification (accuracy > 0.822) and prediction capabilities for CC. Furthermore, six key metabolites indicative of CC progression were identified and validated in additional patient samples, highlighting their potential as biomarkers. Overall, this study establishes a novel method for exosome metabolomics in CC, offering insights for non-invasive early diagnosis and progression prediction on a large scale.

MCM10: A potential biomarker for cervical cancer and precancerous lesions

Cervical cancer remains a significant health burden worldwide, emphasizing the need for early detection and intervention. DNA replication is perturbed in cancer cells, and the minichromosome maintenance protein 10 plays an important role in origin firing. By analyzing the MCM10 mRNA expression in healthy controls, precancerous lesions, and cervical cancer using qRT-PCR, we can infer if it can be considered a biomarker. We collected cervical smear samples from patients and performed MCM10 expression analysis to set up thresholds for risk stratification. We also investigated the HPV status among the patient samples with precancerous lesions and cervical cancer and found 70 % of them to be positive. Our results demonstrated a significant upregulation of MCM10 mRNA expression in tumor samples (n = 40, 7.83 ± 1.2) and precancerous lesions (n = 54, 5.69 ± 1.4) compared to normal (n = 50, 4.27 ± 0.80) with a R2 value of 0.59, confirming its role in the progression and development of cervical cancer. In conclusion, this study emphasizes the potential role of MCM10 as a biomarker. Our study would improve early detection rates, and we propose MCM10-based community screening for risk stratification, prevention, and prognosis.

Pioneering molecular screening for cervical precursor lesions and cervical cancer in sera.

Cervical cancer is a significant public health issue in Mexico and many developing countries. Early detection is crucial for combating this disease. The official screening test for cervical cancer is cytology, but this technique faces several barriers, including methodological, educational, and sociocultural challenges. Liquid-based cytology is an improved version of this test, however it does not address the aforementioned complications. Biomarkers for cervical precursor lesions and cervical cancer can improve timely detection of the disease. A previous study from our group identified four circulating human proteins as potential biomarkers for these conditions. For molecular screening, we selected GAPDH as the biomarker for cervical precursor lesions and HNRNPA1 as the biomarker for cervical cancer -chosen from the three previously identified options based on antibody availability- to be detected in sera. Participants underwent a comprehensive panel of tests, including liquid-based cytology, PCR detection of Human papillomavirus (HPV), colposcopy, and histopathology -when applicable-. The last two tests were used as references for determining sensitivity and specificity, with histopathology being the gold standard for cervical cancer diagnosis. All the participants successfully received colposcopies (n = 99) and only those women with visible or suspected cervical lesions/malignancies were biopsied (n = 62). A subset of randomly selected biopsies underwent p16INK4a immunohistochemistry (n = 36). This study compares the performance of liquid-based cytology with the molecular screening. With colposcopy as reference, liquid-based cytology showed 30% sensitivity and 96% specificity, while the molecular screening showed 90% sensitivity and 43% specificity. With histopathology as reference, liquid-based cytology showed 21% sensitivity and 93% specificity, while the molecular screening showed 85% sensitivity and 61% specificity. The molecular screening outperformed the liquid-based cytology in several areas, including detecting true-positive cases, reducing false-negative cases by 34.62%, application time, simplicity of result´s categories, and acceptance among participants. An ideal screening test requires high sensitivity, maintains moderate specificity, and minimizes false negatives. Our proposed screening test meets these criteria, making it an ideal complement -or alternative- for cervical cancer screening.

Circulating tumor HPV DNA as a specific biomarker for cervical cancer.

The aim of this study was to determine whether circulating tumor human papillomavirus (HPV) DNA is a potential specific biomarker for cervical cancer (CC). This retrospective matched study included 87 patients with cervical intraepithelial neoplasia (CIN), 29 CC patients (FIGO IA1-IVA) and 29 HPV-negative controls at Yuhuangding Hospital of Qingdao University (from July 2022 to September 2023). The digital droplet PCR (ddPCR) was used to detect and quantify ctHPV DNA in the plasma of patients with HPV16, 18, 33, 52, or 58-associated CC. The ctHPV DNA was exclusively detectable in HPV-positive samples, with no detection in patients across various CIN stages (n = 87) or HPV-negative controls (n = 29). Additionally, ctHPV DNA was identified in nine out of 10 late-stage patients (90%) and six out of 19 early-stage patients (31.6%). The ctHPV DNA serves as a specific biomarker for the diagnosis CC. Additionally, this discovery addresses the knowledge gap in ctHPV DNA research in the early stages of CC and promotes clinical diagnosis and treatment strategies.

Numerical Investigation of a Highly Sensitive Plasmonic Refractive Index Sensor for the Detection of Breast and Cervical Cancer Biomarkers

Numerical Investigation of a Highly Sensitive Plasmonic Refractive Index Sensor for the Detection of Breast and Cervical Cancer Biomarkers

Performance of Predictive Models in Cervical Cancer Recurrence: A Systematic Review and Meta-Analysis of Biomarkers and Prognosis

This study investigates the use of Predictive Analytics Frameworks (PAF) for identifying biomarkers of recurrent cervical cancer and predicting prognosis. It addresses the limited comprehensive evaluations of the effectiveness of predictive models in this area, despite the growing application of machine learning in healthcare. The purpose of this systematic review and meta-analysis is to assess the performance of predictive analytics models in terms of sensitivity, accuracy, specificity, and the area under the curve (AUC-ROC) for identifying cervical cancer biomarkers and predicting prognosis. To address this research problem, a systematic review and meta-analysis was conducted, covering studies published between 2014 and 2024. A total of 1,515 studies were initially identified from the PubMed and Scopus databases, with 50 research studies meeting the inclusion criteria. Repeated measures ANOVA and meta-analysis were applied using data collected over an 8-year period to evaluate recurrence trends and the predictive power of various models. The findings suggest that predictive analytics models show significant potential for improving diagnostic accuracy in identifying cervical cancer biomarkers. However, the review also highlights several limitations, including the small number of included studies, heterogeneity across studies, and potential bias in retrospective analyses. In conclusion, while predictive analytics frameworks demonstrate promise in improving cervical cancer prognosis and biomarker identification, further research is required to validate these findings and assess their broader clinical utility. The study underscores the importance of continued exploration of predictive models to enhance decision-making in oncology.

HPV-ferroptosis related genes as biomarkers to predict the prognosis of cervical cancer

BackgroundFerroptosis can be used as a powerful predictor of cancer prognosis. HPV persistent infection is the main cause of cervical cancer, so it is very important to improve the prognosis of patients. Therefore, it is necessary to explore the value of HPV-ferroptosis related genes as prognostic biomarkers of cervical cancer patients.MethodsIn this study, differentially expressed HPV-ferroptosis related genes were obtained from GSE7410, HPV gene set crossed with iron death genes. Five HPV-ferroptosis related genes with prognostic features were finally identified: CYBB, VEGFA, CKB, EFNA1 and HELLS. Multifactorial Cox regression was applied to establish and validate the prognostic model, and drug susceptibility and immune infiltration analyses were also performed.ResultsThe prognostic model was validated in the training set (TCGA) and validation set (GSE44001). Kaplan–Meier curves reveal significant differences in overall survival (OS) between high-risk and low-risk groups. Receiver operating characteristic (ROC) curve reflects the stability and accuracy of the prognostic model established in this study. In terms of immune function, T cell costimulation was better in the low-risk group than in the high-risk group (P < 0.01). The therapeutic effects of cisplatin, paclitaxel, docetaxel and cyclophosphamide, commonly used chemotherapy drugs for cervical cancer, are better in the high-risk group than in the low-risk group (P < 0.001).ConclusionHPV-ferroptosis related gene prognostic model not only has good stability and accuracy in predicting the prognosis of cervical cancer patients, but also has certain guiding value for clinicians in terms of drug sensitivity and immune microenvironment.

The aryl hydrocarbon receptor in environmentally induced cervical cancer: A Narrative review

The aryl hydrocarbon receptor (AhR) plays a crucial role in cellular responses to various environmental pollutants, including several known carcinogens. As a ligand-activated transcription factor, AhR activation modulates the expression of genes involved in critical cellular processes, including detoxification pathways, cell proliferation and differentiation, and immune system regulation. The AhR exhibits pleiotropic effects under normal physiological conditions, contributing to the development and function of various organ systems. AhR activity is important in angiogenesis, cardiomyocyte differentiation, oocyte maturation, oculomotor nerve formation, and hematopoietic stem cell maintenance. Additionally, AhR plays a role in regulating immune cell differentiation and function, maintaining the integrity of the intestinal epithelium and its associated immune system, and mediating UVB-induced DNA damage repair responses in the skin. It acts as a critical environmental sensor, mediating cellular responses to various exogenous ligands. Importantly, activation or inhibition of AhR affects distinct signaling pathways depending on the specific ligand and cellular context. Ligands for the AhR are divided into exogenous or endogenous and have agonistic or antagonistic activity. Recently, the AhR role was determined in cancer development. It can exert both tumor-promoting and tumor-suppressive effects depending on factors such as the specific ligand, cell type, and tissue microenvironment. Emerging evidence suggests that AhR may represent a promising target for immunotherapy and serve as a potential biomarker for cervical cancer. AhR interacts with apoptotic pathway, immune checkpoint system, steroid hormones, and immune cell regulation process in cervical cancer. Despite its potential significance, the precise role of AhR in cervical cancer development and progression is still unknown. In this review, we describe significant roles of AhR in gynecological cancers; e.g., in cervical cancer.

SQLE—a promising prognostic biomarker in cervical cancer: implications for tumor malignant behavior, cholesterol synthesis, epithelial-mesenchymal transition, and immune infiltration

BackgroundCervical cancer, encompassing squamous cell carcinoma and endocervical adenocarcinoma (CESC), presents a considerable risk to the well-being of women. Recent studies have reported that squalene epoxidase (SQLE) is overexpressed in several cancers, which contributes to cancer development.MethodsRNA sequencing data for SQLE were obtained from The Cancer Genome Atlas. In vitro experiments, including colorimetry, colony formation, Transwell, RT-qPCR, and Western blotting were performed. Furthermore, a transplanted CESC nude mouse model was constructed to validate the tumorigenic activity of SQLE in vivo. Associations among the SQLE expression profiles, differentially expressed genes (DEGs), immune infiltration, and chemosensitivity were examined. The prognostic value of genetic changes and DNA methylation in SQLE were also assessed.ResultsSQLE mRNA expression was significantly increased in CESC. ROC analysis revealed the strong diagnostic ability of SQLE toward CESC. Patients with high SQLE expression experienced shorter overall survival. The promotional effects of SQLE on cancer cell proliferation, metastasis, cholesterol synthesis, and EMT were emphasized. DEGs functional enrichment analysis revealed the signaling pathways and biological processes. Notably, a connection existed between the SQLE expression and the presence of immune cells as well as the activation of immune checkpoints. Increased SQLE expressions exhibited increased chemotherapeutic responses. SQLE methylation status was significantly associated with CESC prognosis.ConclusionSQLE significantly affects CESC prognosis, malignant behavior, cholesterol synthesis, EMT, and immune infiltration; thereby offering diagnostic and indicator roles in CESC. Thus, SQLE can be a novel therapeutic target in CESC treatment.

Up-regulated DSG2 promotes tumor growth and reduces immune infiltration in cervical cancer

BackgroundDesmoglein-2 (DSG2) has been reported to play pivotal roles in various diseases. However, its roles in cervical cancer (CC) remain insufficiently elucidated. Here, we aimed to comprehensively explore the functional mechanisms of DSG2 in CC using bioinformatics and experimental methods. MethodsSeveral online databases, including Gene Expression Profiling Interactive Analysis (GEPIA), ONCOMINE, LinkedOmics, MetaScape, Human protein atlas (HPA), OMICS and single-cell RNA sequencing (scRNA-seq) data were used to explore the expression, prognosis, gene mutations, and potential signaling pathway of DSG2 in CC. Quantitative real-time PCR (qRT-PCR) and western blotting were used to measure DSG2 expression in collected samples. Experimental assays were conducted to verify the effects of dysregulated DSG2 on cervical cell lines in vitro. ResultsBioinformatic analyses revealed that DSG2 was significantly up-regulated in CC compared to normal cervical tissues at both mRNA and protein levels. Elevated DSG2 levels were also associated with poor prognosis and clinical parameters (e.g., cancer stages, tumor grade, nodal metastasis status, etc.). DSG2 expression was predominantly observed in epithelial cells, increasing with disease progression on a single-cell resolution. Additionally, up-regulation of DSG2 significantly enhanced tumor purity by reducing the infiltration of immune cells (e.g., B cells, T cells, NK cells, etc.). Over-expression of DSG2 was further validated in collected CC samples at both mRNA and protein levels. Knockdown of DSG2 markedly reduced the proliferation and invasion of CC cell lines in vitro. ConclusionsIn summary, elevated levels of DSG2 were significantly associated with poor prognosis and diminished immune infiltration in CC. Thus, DSG2 may serve as a potential therapeutic and diagnostic biomarker for CC.

Machine learning analysis of oxidative stress-related phenotypes for specific gene screening in ovarian cancer.

Oxidative stress serves a crucial role in tumor development. However, the relationship between ovarian cancer and oxidative stress remains unknown. We aimed to create an oxidative stress-related prognostic signature to enhance the prognosis prediction of CC patients using bioinformatics. The genes differentially expressed and associated with oxidative stress were extracted with the help of "limma" packages. The model for prognosis was created using Multivariate Cox regression analysis to determine the risk related to the genes related to oxidative stress. Patients were categorized as low-risk or high-risk based on the median score. The receiver operation characteristic (ROC) and survival curves were used to evaluate the predictive effect of the prognostic signature. We utilized quantitative real-time PCR to assess the expression levels of key genes associated with oxidative stress in ovarian cancer cell lines (SKOV3, OVCAR3, and HeyA8) and normal ovarian epithelial cells (HOSEpiC). A signature comprising seven genes associated with oxidative stress was developed to prognosticate patients with ovarian cancer. Overall survival (OS) of the patient having CC was determined using Kaplan-Meier analysis. It was found that patient with a higher risk score had lower OS than the low-risk score. The signature of genes associated with oxidative stress was found to be independently prognostic for 1, 2, and 3 years. Further research found that the expression levels of nine hub genes had a strong association with patient outcomes. Our analysis revealed a higher expression of CX3CR1 in ovarian cancer cell lines compared with normal cells. To deploy a novel oxidative stress-related prognostic signature as an independent biomarker in cervical cancer, we developed and validated it.

Methylation-related differentially expressed genes as potential prognostic biomarkers for cervical cancer

AimTo discover novel methylation-related differentially expressed genes (MRDEGs) for cervical cancer, with a focus on their potential for early diagnosis and prognostic assessment. Materials & methodsWe integrated data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. TCGA-MRDEGs were identified by analyzing differentially methylated genes (DMGs) and their correlation with gene expression. We examined GEO datasets GSE39001, GSE9750, and GSE46306 for GEO-MRDEGs. Overlapping MRDEGs were subjected to overall survival (OS) analysis to identify prognostic markers. The expression and methylation levels of these genes were validated in a total of 30 tissue samples, comprising 20 from cervical cancer patients and 10 from normal cervical tissues, using qRT-PCR and MassARRAY EpiTYPER Assay. ResultsA total of 314 TCGA-MRDEGs and 40 GEO-MRDEGs were identified. Intersection analysis yielded 10 overlapping MRDEGs. Notably, NOVA1, GSTM5, TRHDE, and CXCL12 were found to have reduced expression and increased methylation in cervical cancer, which correlated with poor prognosis. The methylation status and expression levels of these genes were confirmed in tissue specimens. ConclusionWe identified four MRDEGs as potential prognostic biomarkers for cervical cancer. Their clinical utility is highlighted, but further validation in larger cohorts is required to establish their clinical significance.

Novel Serum Protein Biomarkers for Precancerous Cervical Lesions and Cervical Cancer

Novel Serum Protein Biomarkers for Precancerous Cervical Lesions and Cervical Cancer

Identification of key genes associated with cervical cancer based on bioinformatics analysis

BackgroundCervical cancer has extremely high morbidity and mortality, and its pathogenesis is still in the exploratory stage. This study aimed to screen and identify differentially expressed genes (DEGs) related to cervical cancer through bioinformatics analysis.MethodsGSE63514 and GSE67522 were selected from the GEO database to screen DEGs. Then GO and KEGG analysis were performed on DEGs. PPI network of DEGs was constructed through STRING website, and the hub genes were found through 12 algorithms of Cytoscape software. Meanwhile, GSE30656 was selected from the GEO database to screen DEMs. Target genes of DEMs were screened through TagetScan, miRTarBase and miRDB. Next, the hub genes screened from DEGs were merged with the target genes screened from DEMs. Finally, ROC curve and nomogram analysis were performed to assess the predictive capabilities of the hub genes. The expression of these hub genes were verified through TCGA, GEPIA, qRT-PCR, and immunohistochemistry.ResultsSix hub genes, TOP2A, AURKA, CCNA2, IVL, KRT1, and IGFBP5, were mined through the protein-protein interaction network. The expression of these hub genes were verified through TCGA, GEPIA, qRT-PCR, and immunohistochemistry, and it was found that TOP2A, AURKA as well as CCNA2 were overexpressed and IGFBP5 was low expression in cervical cancer.ConclusionsThis study showed that TOP2A, AURKA, CCNA2 and IGFBP5 screened through bioinformatics analysis were significantly differentially expressed in cervical cancer samples compared with normal samples, which might be biomarkers of cervical cancer.

Simultaneous immunodetection of multiple cervical cancer biomarkers based on a signal-amplifying redox probes/polyethyleneimine-coated gold nanoparticles/2D tungsten disulfide/graphene oxide nanocomposite platform

To advance cervical cancer diagnostics, we propose a state-of-the-art label-free electrochemical immunosensor designed for the simultaneous detection of multiple biomarker proteins (p16INK4a, p53, and Ki67). This immunosensor is constructed using a polyethyleneimine-coated gold nanoparticles/2D tungsten disulfide/graphene oxide (PEI-AuNPs/2D WS2/GO) composite-modified three-screen-printed carbon electrode (3SPCE) array. The 2D WS2/GO hybrid provides a large specific surface area for supporting well-dispersed PEI-AuNPs and adsorbed redox-active species, enhancing overall performance. The PEI-AuNPs-decorated 2D WS2/GO composite not only improves electrode conductivity but also increases the antibody loading capacity. Redox-active species, including Cd2+ ions, 2,3-diaminophenazine (DAP), and methylene blue (MB), serve as distinct signaling compounds to quantitatively detect the cervical cancer biomarkers p16INK4a, p53, and Ki67, respectively. Additionally, the immunosensor demonstrates the detection with high sensitivity, good storage stability, high selectivity, and acceptable reproducibility. This immunosensor demonstrates a good linear relationship with the logarithm of protein concentrations. Additionally, the immunosensor also demonstrates high sensitivity, good storage stability, high selectivity, and acceptable reproducibility. Our promising results and the successful application of the immunosensor in detecting three tumor markers in human serum highlight its potential for clinical diagnosis of cervical cancer.

Exosomal lncRNA USP30-AS1 activates the Wnt/β-catenin signaling pathway to promote cervical cancer progression via stabilization of β-catenin by USP30.

Cervical cancer (CC) remains a major cause of cancer-related mortality among women globally. Long noncoding RNAs (lncRNAs) play crucial regulatory roles in various cancers, including CC. This study investigates the function of a novel lncRNA, USP30 antisense RNA 1 (USP30-AS1), in CC tumorigenesis. We analyzed USP30-AS1 expression using RT-qPCR and conducted in vitro loss-of-function assays, as well as in vivo assays, to evaluate the effects of USP30-AS1 silencing on CC cell growth and migration. Additional mechanistic experiments, including RNA pull-down, RNA immunoprecipitation (RIP), and co-immunoprecipitation (Co-IP) assays, were performed to elucidate the regulatory mechanisms influenced by USP30-AS1. We discovered that USP30-AS1 is overexpressed in CC tissues and cells. Silencing USP30-AS1 significantly reduced cell proliferation, migration, invasion, and tumor growth. Moreover, USP30-AS1 was found to modulate the expression of ubiquitin-specific peptidase 30 (USP30) by sponging microRNA-2467-3p (miR-2467-3p) and recruiting the FUS RNA binding protein (FUS), thereby stabilizing β-catenin and activating the Wnt/β-catenin signaling pathway. These findings suggest that USP30-AS1 enhances CC cell growth and migration through the miR-2467-3p/FUS/USP30 axis, highlighting its potential as a biomarker for CC.

Portable Device with Nicking Enzyme Enhanced Special RCA on μPADs toward Sensitive Detection of High-Risk HPV Infection.

Development of an accurate, rapid, and cost-effective portable device is in high demand for point-of-care molecular diagnosis toward disease screening. Here we report a one-pot homogeneous isothermal assay that leverages nicking endonuclease and minimum secondary structured rolling circle amplification (N-MSSRCA) for fast and sensitive quantification of nucleic acids on distance microfluidic paper-based analytical devices (dμPAD) by a portable custom-made fluorescence detector. Human papillomavirus (HPV) oncogenic E7 mRNA as the biomarker for cervical cancer was used as the model analyte. N-MSSRCA integrates ligase for target recognition, the nicking enzyme for primer generation, and the dual function of the Phi29 DNA polymerase for both on- and off-loop amplification. The proposed method was capable of detecting 1 and 10 fM of the analyte using the microplate reader and portable detector with dμPAD, respectively, with ∼1 h assay time. A cohort study of 40 cervical swab samples shows N-MSSRCA reached positive and negative predictive values of 87.5% and 93.5% using the portable detector with dμPAD, compared to 91.67% and 100% using the microplate reader. N-MSSRCA demonstrates potential in early screening of high-risk HPV infection as a generic strategy to detect various nucleic acids in point-of-care scenarios.

Vaginal microbial profile of cervical cancer patients receiving chemoradiotherapy: the potential involvement of Lactobacillus iners in recurrence

The vaginal microbiome is an immune defense against reproductive diseases and can serve as an important biomarker for cervical cancer. However, the intrinsic relationship between the recurrence and the vaginal microbiome in patients with cervical cancer before and after concurrent chemoradiotherapy is poorly understood. Here, we analyzed 125 vaginal microbial profiles from a patient cohort of stage IB–IVB cervical cancer using 16S metagenomic sequencing and deciphered the microbial composition and functional characteristics of the recurrent and non-recurrent both before and after chemoradiotherapy. We demonstrated that the abundance of beneficial bacteria and stability of the microbial community in the vagina decreased in the recurrence group, implying the unique characteristics of the vaginal microbiome for recurrent cervical cancer. Moreover, using machine learning, we identified Lactobacillus iners as the most important biomarker, combined with age and other biomarkers (such as Ndongobacter massiliensis, Corynebacterium pyruviciproducens ATCC BAA-1742, and Prevotella buccalis), and could predict cancer recurrence phenotype before chemoradiotherapy. This study prospectively employed rigorous bioinformatics analysis and highlights the critical role of vaginal microbiota in post-treatment cervical cancer recurrence, identifying promising biomarkers with prognostic significance in the context of concurrent chemoradiotherapy for cervical cancer. The role of L. iners in determining chemoradiation resistance in cervical cancer warrants further detailed investigation. Our results expand our understanding of cervical cancer recurrence and help develop better strategies for prognosis prediction and personalized therapy.

Predictive value of C reactive protein (CRP) and D-dimer in patients with advanced cervical cancer treated with sintilimab and anlotinib.

e17525 Background: The Sintilimab plus Anlotinib in patients with advanced cervical cancer trial was a single-arm, phase II study that showed promising activity of the programmed death-1 (PD-1) inhibitor sintilimab plus the vascular endothelial growth factor receptor inhibitor Anlotinib in patients with advanced cervical cancer. We aimed to identify prognostic values of inflammation biomarkers and coagulation biomarkers in advanced cervical cancer treated with Sintilimab and Anlotinib. Methods: We conducted a post-hoc analysis of the data from the ALTER-C201 study (Clinical trial information: ChiCTR1900023015). The predictive value of coagulation variables and inflammation variables was evaluated by receiver operating characteristic (ROC) curves. Through Cox hazards regression models, prognostic factors were determined for overall survival (OS). Survival curves were visualized by Kaplan–Meier method and compared through Log-rank analysis. Results: We involved 41 patients and followed up for 38.0 (range, 0.6–44.0) months. According to the ROC curve, the predictive values of baseline CRP and D-dimer are better than other indicators, with area under the curve (AUC) values of 0.748 and 0.848, respectively. The cut-off values for D-dimer and CRP are 1.75ug/ml and 10.9mg/L, respectively. Through regression analysis, we demonstrated that CRP (HR 2.591; 95%CI 1.099–6.106; P = 0.030) and D-dimer (HR 2.669; 95%CI 1.154–6.173; P = 0.022) were independent prognostic factors. Compared to patients with CRP ≥ 10.9mg/L, those with CRP &lt; 10.9mg/L have a longer OS (28.93 months, 95% CI, 15.23 to not reached v 10.57 months, 95% CI, 6.14 to not reached; log-rank test, P = 0.007). Compared to patients with D-dimer ≥ 1.75ug/ml, those with D-dimer &lt; 1.75ug/ml have a longer OS (28.93 months, 95% CI, 17.09 to not reached v 10.73 months, 95% CI, 4.63 to not reached; log-rank test, P = 0.005). Conclusions: CRP and D-dimer predict survival in advanced cervical cancer patients undergoing combined ICI/ VEGF-TKI therapy. We advocate further work to validate utilisation of CRP and D-dimer as prognostic biomarkers for advanced cervical cancer in clinical practice.

Plasma-Derived Exosomal tRF-Phe-GAA-001 and tRF-Gly-GCC-037 as Novel Diagnostic Biomarkers for Cervical Cancer

Plasma-Derived Exosomal tRF-Phe-GAA-001 and tRF-Gly-GCC-037 as Novel Diagnostic Biomarkers for Cervical Cancer