The predictive value of serum inflammatory markers for the severity of cervical lesions.

OBJECTIVE: Exploring the predictive value of NLR, PLR, MLR, and SII for the severity of cervical cancer screening abnormalities in patients. METHODS: A retrospective analysis was conducted on the data of 324 patients suspected of cervical lesions due to abnormal TCT and/or HPV in our hospital from January 2023 to December 2023, who underwent colposcopy. The pathological results of colposcopic biopsy confirmed that there were 140 cases of chronic cervicitis, which classified as the group without cervical lesions. The cervical lesion group included 184 cases, including 91 cases of LSIL, 71 cases of HSIL, and 22 cases of cervical cancer. Compared the differences in preoperative peripheral blood NLR, PLR, MLR, and SII among different groups of patients, and evaluated their predictive value for the severity of cervical lesions using Receiver Operating Characteristic (ROC) curves. RESULTS: The levels of NLR, PLR, and SII in the group without cervical lesions were lower than those in the group with cervical lesions (p < 0.05), and there was no statistically significant difference in MLR (p > 0.05). The comparison of NLR among LSIL, HSIL, and cervical cancer groups showed statistically significant differences (p < 0.05), while PLR, MLR, and SII showed no statistically significant differences (p > 0.05). The AUC of peripheral blood NLR, PLR, and SII for predicting cervical lesions were 0.569, 0.582, and 0.572, respectively. The optimal cutoff values were 2.3,176.48, and 603.56. The sensitivity and specificity were 38.6% and 73.6%, 28.8% and 85.7%, 37.5% and 76.4%, respectively. At the same time, the joint testing of the three had the highest efficiency, with sensitivity of 69% and specificity of 45%. CONCLUSION: Although the peripheral blood NLR, PLR, and SII of the cervical lesions patients were higher than those without cervical lesions in cervical cancer screening abnormal patients, the predictive ROC curve discrimination was low. Therefore, it is not recommended to use preoperative peripheral blood inflammatory markers as markers for cervical cancer screening abnormal patient diversion.

Identification of exosomal circSLC26A4 as a liquid biopsy marker for cervical cancer.

OBJECTIVE: Circular RNA SLC26A4 (circSLC26A4) functions as an oncogene in the initiation and progression of cervical cancer (CC). However, the clinical role of plasma exosomal circSLC26A4 in CC is poorly known. This study aims to develop an accurate diagnostic method based on circulating exosomal circSLC26A4. METHODS: In this study, exosomal circSLC26A4 derived from CC cell lines (CaSki, SiHa, and HeLa) and human cervical epithelial cells (HcerEpic) was measured and compared using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Additionally, 56 volunteers, including 18 CC patients, 18 cervical high-grade squamous intraepithelial lesion (HSIL) patients, and 20 healthy volunteers, were enrolled. qRT-PCR was also performed to measure the plasma exosomal circSLC26A4 levels in all participants. RESULTS: The exosomal circSLC26A4 expression level derived from CC cells was significantly elevated compared to it derived from HcerEpic cells. Plasma exosomal circSLC26A4 levels in CC patients were significantly higher than in healthy women and HSIL patients (P < 0.05). In addition, high plasma exosomal circSLC26A4 expression was positively associated with lymph node metastasis and FIGO stage (all P < 0.05). However, no significant correlation was found between plasma exosomal circSLC26A4 expression and age, intravascular cancerous embolus, and perineural invasion (P > 0.05). CONCLUSIONS: The high exosomal circSLC26A4 expression is closely related to the occurrence of CC. Plasma exosomal circSLC26A4 can be used as a diagnostic marker for CC.

Prediction of outcomes after chemoradiotherapy for cervical cancer by neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio.

BACKGROUND: Cervical cancer ranks as the second most fatal tumour globally among females. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been widely applied to the diagnosis of cancers. METHODS: The clinicopathologic data of 180 patients with stage IB2-IIB cervical cancer who underwent radical concurrent chemoradiotherapy from January 2018 to December 2019 were retrospectively analysed. Receiver operating characteristic (ROC) curves were plotted to analyse the optimal cut-off values of NLR and PLR for predicting the therapeutic effects of concurrent chemoradiotherapy. The associations of PLR and other clinicopathological factors with 1-year survival rates were explored through univariate analysis and multivariate Cox regression analysis, respectively. RESULTS: NLR was significantly associated with the therapeutic effects of neoadjuvant therapy, with the optimal cut-off value of 2.89, area under the ROC curve (AUC) of 0.848 (95% confidence interval [CI]: 0.712-0.896), sensitivity of 0.892 (95% CI: 0.856-0.923) and specificity of 0.564 (95% CI: 0.512-0.592). PLR had a significant association with the therapeutic effects of neoadjuvant therapy, with the optimal cut-off value of 134.27, AUC of 0.766 (95% CI: 0.724-0.861), sensitivity of 0.874 (95% CI: 0.843-0.905) and specificity of 0.534 (95% CI: 0.512-0.556). Lymphatic metastasis ([95% CI: 1.435-5.461], [95% CI: 1.336-4.281], depth of invasion ([95% CI: 1.281-3.546], [95% CI: 1.183-3.359]) and tumour size ([95% CI: 1.129-3.451], [95% CI: 1.129-3.451]) were independent factors influencing the overall survival and disease-free survival (DFS) of patients with cervical cancer. NLR (95%CI: 1.256-4.039) and PLR (95%CI:1.281-3.546) were also independent factors affecting DFS. CONCLUSION: NLR and PLR in the peripheral blood before treatment may predict DFS of patients with stage IB2-IIB cervical cancer.

The clinicopathologic data of 180 patients with stage IB2-IIB cervical cancer who underwent radical concurrent chemoradiotherapy were retrospectively analysed. Receiver operating characteristic curves showed that neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were significantly associated with the therapeutic effects of neoadjuvant therapy. Univariate and multivariate regression analysis revealed that lymphatic metastasis, depth of invasion and tumour size were independent factors influencing the overall survival and disease-free survival (DFS) of patients with cervical cancer. NLR and PLR in the peripheral blood before treatment may predict the DFS of patients with stage IB2-IIB cervical cancer.

The complement regulatory protein CD46 serves as a novel biomarker for cervical cancer diagnosis and prognosis evaluation.

Background: CD46 has been revealed to be a key factor in malignant transformation and cancer treatment. However, the clinical significance of CD46 in cervical cancer remains unclear, and this study aimed to evaluate its role in cervical cancer diagnosis and prognosis evaluation. Methods: A total of 180 patients with an initial diagnosis of cervical cancer were enrolled at Taizhou Hospital of Zhejiang Province, China. The plasma levels of soluble CD46 (sCD46) and the expression of membrane-bound CD46 (mCD46) were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC), respectively. Results: CD46 was found to be significantly upregulated in cervical cancer tissues vs. normal tissues, while no CD46 staining was detected in paired adjacent noncancerous tissues. CD46 staining was more pronounced in cancer cells than in stromal cells in situ (in tissues). Moreover, the plasma levels of sCD46 were able to some extent discriminate between cancer patients and healthy women (AUC=0.6847, 95% CI:0.6152-0.7541). Analysis of Kaplan-Meier survival curves revealed that patients with low CD46 expression had slightly longer overall survival (OS) than patients with high CD46 expression in the tumor microenvironment, but no significant difference. Univariate Cox regression analysis revealed that CD46 (P=0.034) is an independent risk factor for OS in cervical cancer patients. Conclusion: The present study demonstrated that cervical cancer patients exhibit aberrant expression of CD46, which is closely associated with a poor prognosis, suggesting that CD46 plays a key role in promoting cervical carcinogenesis and that CD46 could serve as a promising potential target for precision therapy for cervical cancer.

Peripheral blood immune cell parameters in patients with high-grade squamous intraepithelial lesion (HSIL) and cervical cancer and their clinical value: a retrospective study.

Objective: The objective of this study was to delineate the profile of peripheral blood lymphocytic indices in patients afflicted with high-grade squamous intraepithelial lesions (HSIL) and cervical neoplasms, and to elucidate the correlation of these hematologic markers with the clinicopathological spectra in individuals diagnosed with cervical carcinoma. Methods: We adopted a retrospective case-control modality for this investigation. An aggregate of 39 HSIL patients and 42 cervical carcinoma patients, who were treated in our facility from July 2020 to September 2023, were meticulously selected. Each case of cervical malignancy was confirmed through rigorous histopathological scrutiny. Concomitantly, 31 healthy female individuals, who underwent prophylactic health evaluations during the corresponding timeframe, were enlisted as the baseline control group. We systematically gathered and analyzed clinical demographics, as well as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), from peripheral blood samples. Pearson's correlation coefficient was deployed to dissect the interrelation between peripheral NLR and PLR concentrations and the clinicopathological features in the cervical cancer group. Results: Inter-group comparative analysis unveiled statistically substantial variances in the PLR and NLR values among the tripartite clusters (F = 36.941, 14.998, P < 0.001, respectively). Although discrepancy in NLR (P = 0.061) and PLR (P = 0.759) measures between the groups of cervical carcinoma and HSIL was not statistically appreciable, these indices were markedly elevated in the cervical carcinoma faction as juxtaposed with the normative control group (t = 5.094, 5.927; P < 0.001 for both parameters). A discernible gradation in peripheral blood PLR and NLR concentrations was noted when stratified by clinical stage and the profundity of myometrial invasion in cervical cancer subjects (P < 0.001). The correlation matrix demonstrated a positive liaison between peripheral blood PLR and the clinical gradation, as well as the invasiveness of the neoplastic cells into the muscularis propria (P < 0.05); a similar trend was observed with the NLR values (P < 0.05). Conclusion: Augmented NLR and PLR levels in peripheral blood specimens are indicative of HSIL and cervical malignancy. These hematological parameters exhibit a pronounced interconnection with clinical staging and muscular wall penetration depth, serving as potential discriminative biomarkers for the diagnosis and prognosis of cervical cancer.

Prognostic prediction of oxidative stress related hematological biomarkers in locally advanced cervical cancer patients undergoing chemoradiotherapy.

OBJECTIVE: This investigation aimed to develop and validate a novel oxidative stress score for prognostic prediction in locally advanced cervical cancer (LACC) patients receiving chemoradiotherapy. METHODS: A total of 301 LACC patients were enrolled and randomly divided into a training and a validation set. The association between oxidative stress parameters and prognosis was analyzed for oxidative stress score (OSS) establishment. A Cox regression model was conducted for overall survival (OS) and progression-free survival (PFS). A nomogram prediction model was developed using independent prognostic factors from the training set and validated in the validation set. RESULTS: A novel OSS was established with four oxidative stress parameters, including albumin, total bilirubin, blood urea nitrogen, and lactate dehydrogenase. Multivariate regression analysis identified OSS as an independent prognostic factor for OS (p = 0.001) and PFS (p < 0.001). A predictive nomogram based on the OSS was established and validated. The C-indexes of the nomogram in the training set were 0.772 for OS and 0.781 for PFS, while in the validation set the C-indexes were 0.642 for OS and 0.621 for PFS. CONCLUSION: This study confirmed that preoperative OSS could serve as a useful independent prognostic factor in LACC patients who received CCRT.

A novel prognostic biomarker in progression free survival for patients with cervical cancer, glucose to c-reactive protein ratio (GCR).

BACKGROUND: Cervical cancer is a tumor with high morbidity and mortality. The importance of inflammatory and metabolic parameters affecting progression-free survival (PFS) and overall survival (OS) has been investigated more intensively recently. We aimed to investigate the effect of glucose/c-reactive protein (CRP) ratio [GCR], which shows these two parameters together, on PFS in cervical cancer. METHODS: We retrospectively included 90 patients with adenocarcinoma and squamous cell carcinoma of the cervix. The effects of clinical variables, inflammatory and glycemic parameters on PFS and OS were analyzed by Kaplan-Meier method. The data were compared with the healthy control group of 90 individuals using the independent t test. The effect of parameters on mortality was analyzed using ROC curves and cut off values were determined. RESULTS: Glucose, CRP, CRP/lymphocyte ratio (CLR) and GCR were statistically significant in predicting mortality (p < 0.05). Disease stage, glucose, CRP, CLR and GCR were associated with overall survival. CRP, CLR and GCR were associated with progression-free survival (p < 0.05). In multivariate analysis, GCR was prognostic for PFS (p = 0.025). GCR was statistically significant while compared with the patient and healthy control group (p < 0.001). CONCLUSION: In cervical cancer, GCR rate was found to be prognostic independent of stage. Higher GCR rate was associated with longer PFS duration.

A novel nomogram based on inflammation biomarkers for predicting radiation cystitis in patients with local advanced cervical cancer.

BACKGROUNDS: Platelet-to-albumin ratio (PAR) is a new systemic inflammatory prognostic indicator associated with many inflammatory diseases. However, its role in radiation cystitis (RC) is obscure. This study aimed to explore whether PAR could be used as an effective parameter for predicting the RC risk in local advanced cervical cancer (CC) treated with radiotherapy. METHODS: A total of 319 local advanced CC patients who received radical radiotherapy at Fujian Cancer Hospital were enrolled between December 2018 and January 2021. Demographics and clinical parameters were retrospectively analyzed. Univariate and multivariate analyses were used to identify the risk factors for RC. Backward and stepwise regression was applied to construct two monograms-one with primary significant factors and the other with extra inflammatory biomarkers. A DeLong test was applied to compare the prediction abilities of two nomograms. Calibration curves and decision curve analysis (DCA) evaluated its prediction consistency, discrimination ability, and clinical net benefit. RESULTS: Univariate analysis showed that age, tumor size, stage, total radiation dose, pelvic radiation dose, Systemic Immune-Inflammation Index (SII), platelet-to-lymphocyte ratio (PLR), and PAR were significantly associated with RC occurrence (all p < 0.05). Multivariate analyses indicated that age, tumor size, stage, total radiation dose, and PAR were independent factors (all p < 0.05). Then, the area under curve (AUC) value of the nomogramSII+PAR was higher (AUC = 0.774) compared to that of the baseline nomogram (AUC = 0.726) (pDelong = 0.02). Also, the five-cross validation confirmed the stability of the nomogramSII+PAR. Moreover, the calibration curve and DCA exhibited the nomograms' good prediction consistency and clinical practicability. CONCLUSIONS: PAR and SII could be valued for CC patients who are treated with radiation therapy. The nomogram based on PAR and SII could stratify patients who need extra intervention and nursing care to prevent bladder radiation damage and improve patients' quality of life.

Cervical cancer biomarker screening based on Raman spectroscopy and multivariate statistical analysis.

Cervical cancer (CC) stands as one of the most prevalent malignancies among females, and the examination of serum tumor markers(TMs) assumes paramount significance in both its diagnosis and treatment. This research delves into the potential of combining Surface-Enhanced Raman Spectroscopy (SERS) with Multivariate Statistical Analysis (MSA) to diagnose cervical cancer, coupled with the identification of prospective serum biomarkers. Serum samples were collected from 95 CC patients and 81 healthy subjects, with subsequent MSA employed to analyze the spectral data. The outcomes underscore the superior efficacy of Partial Least Squares Discriminant Analysis (PLS-DA) within the MSA framework, achieving predictive accuracy of 97.73 %, and exhibiting sensitivities and specificities of 100 % and 95.83 % respectively. Additionally, the PLS-DA model yields a Variable Importance in Projection (VIP) list, which, when coupled with the biochemical information of characteristic peaks, can be utilized for the screening of biomarkers. Here, the Random Forest (RF) model is introduced to aid in biomarker screening. The two findings demonstrate that the principal contributing features distinguishing cervical cancer Raman spectra from those of healthy individuals are located at 482, 623, 722, 956, 1093, and 1656 cm-1, primarily linked to serum components such as DNA, tyrosine, adenine, valine, D-mannose, and amide I. Predictive models are constructed for individual biomolecules, generating ROC curves. Remarkably, D-mannose of V (C-N) exhibited the highest performance, boasting an AUC value of 0.979. This suggests its potential as a serum biomarker for distinguishing cervical cancer from healthy subjects.

Cell-Free Human Papillomavirus DNA Is a Sensitive Biomarker for Prognosis and for Early Detection of Relapse in Locally Advanced Cervical Cancer.

PURPOSE: Human papillomavirus (HPV) is the cause of the majority of cervical cancer cases and has been showed to be released as cell-free tumor DNA (ctHPV DNA) into the circulation. Here, we analyze if ctHPV DNA could be used as a prognostic biomarker and/or to detect relapse earlier than traditional methods in locally advanced cervical cancer (LACC). EXPERIMENTAL DESIGN: A total of 74 patients with LACC were included; 66of 74 were positive for 13 high-risk HPV types on a bead-based assay of tumor biopsy samples. HPV-type-specific droplet digital PCR assays were developed. Longitudinal plasma samples were then analyzed for the biopsy-verified HPV type for each patient. In total, 418 plasma samples were analyzed. Patients were followed for a median of 37 months. Results were correlated to tumor and clinical characteristics. RESULTS: Of the pretreatment plasma samples, 92.4% were positive for ctHPV DNA. Persistent ctHPV DNA in end-of-treatment, early follow-up (1-2 months after end-of-treatment), or tumor evaluation (3-4 months after end-of-treatment) plasma was correlated with worse progression-free survival (P < 0.001) compared with if ctHPV DNA was not found. The positive predictive value of ctHPV status at early follow-up for predicting disease progression was 87.5%, and the negative predictive value was 89.3%. ctHPV DNA was found in plasma before relapse was diagnosed using radiology in all patients (n = 10) who experienced relapse after complete clinical response to treatment with a median 315 days lead time. CONCLUSIONS: ctHPV DNA in follow-up plasma is a promising prognostic biomarker in patients with LACC, useful for analysis of response to therapy and for early detection of relapse.

Accuracy of surveillance serum squamous cell carcinoma antigen for cervical cancer recurrence after definitive chemoradiation.

OBJECTIVE: Recurrence remains a significant clinical problem for patients with cervical cancer, and early detection may improve outcomes. Serum squamous cell carcinoma antigen (SCCA) is a biomarker of prognosis and response to chemoradiotherapy. We hypothesized that elevated serum SCCA during surveillance is sensitive and specific for recurrence. METHODS: Pre-treatment and follow-up serum SCCA from patients treated with definitive-intent radiotherapy were measured via enzyme-linked immunosorbent assay in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory and analyzed retrospectively. Follow-up SCCA was defined as the value closest to recurrence, or as last available for patients without recurrence. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of follow-up SCCA for recurrence was determined for the whole cohort (Cohort 1), for patients with elevated (Cohort 2), and normal pre-treatment SCCA (Cohort 3). Patterns of failure were also evaluated. RESULTS: Of 227 patients in Cohort 1, 23% experienced recurrence, and 17% died of cervical cancer. Mean follow-up SCCA was 0.9 (±2.5) for patients with no recurrence and 6.0 (±18.7) for patients with recurrence (p=0.02). Sensitivity, specificity, PPV, and NPV of follow-up SCCA for recurrence in Cohort 1 were 38.5%, 97.1%, 80%, and 84.2%, and for patients in Cohort 2 were 54.5%, 95%, 78.3%, and 86.5%, respectively. Four of 86 patients in Cohort 3 had an elevated follow-up SCCA, two of these at the time of recurrence. Elevated pre-treatment SCCA and follow-up SCCA were associated with isolated pelvic recurrence. CONCLUSIONS: Surveillance serum SCCA has high specificity and NPV for recurrence, and may be of limited utility in patients with normal pre-treatment SCCA.

Clinical Significance of Serum SCC Levels Before Treatment for Locally Advanced Cervical Squamous Cell Carcinoma.

BACKGROUND/AIM: Although serum squamous cell carcinoma (SCC) antigen values are known to be useful in predicting the prognosis of cervical SCC, they have only been examined in a cursory manner. This study aimed to meticulously investigate the clinical significance of serum SCC antigen levels in patients with locally advanced cervical squamous cell carcinoma (LACSC). PATIENTS AND METHODS: The study included patients who were diagnosed with local stage (T-stage) 1b3/2/3 LACSC and underwent initial treatment at our institute between January 2006 and December 2016 (T-1b3: n=30; T-2: n=75; T-3: n=34). The patients were divided into three groups based on pre-treatment SCC values, and differences in clinical background, laboratory and pathology findings, and prognosis were examined. RESULTS: No significant difference in the SCC distribution was observed among the T-1b3/2/3 cases with elevated SCC levels. In stages T-1b3, T-2, and T-3, most recurrences in the SCC-High group were distant (T-1b3: three out of five recurrences; T-2: six out of seven recurrences; T-3: four out of eight recurrences), while most recurrences in the SCC-Low group were pelvic (T-1b3: two out of three recurrences; T-2: eight out of eight recurrences; T-3: three out of three recurrences). CONCLUSION: In LACSC, serum SCC antigen levels before treatment correlate strongly with the recurrence site. Patients with low levels should be closely monitored for local recurrence, whereas those with high levels warrant vigilance for distant recurrence.

Frequency shift Raman-based sensing of serum MicroRNA for ultrasensitive cervical cancer diagnosis.

Cervical cancer is the most common gynaecological tumor. The development of a sensor for the ultrasensitive detection of cervical cancer is significant in guaranteeing its prognosis. Herein, we proposed a novel surface-enhanced Raman scattering (SERS) analysis platform using a frequency shifts-based sensing model for rapid and ultrasensitive microRNA (miRNA) assay. During the analysis process, miR-21 can be captured by the single-stranded DNA (ssDNA) modified on the platform which is complementary pairing with miR-21. The connection of miR-21 can lead to the variation of the molecular weight and result in the deformation extent of the Raman report molecule 6Thioguanine (6TG); thus, the peak at 1301 cm-1 due to the ring C-N stretches of 6TG shifts to lower frequency. The detection limit (LOD) of the proposed SERS analysis platform is as low as 8.32 aM. Moreover, the platform also has excellent specificity and repeatability, with the relative standard deviation (RSD) value of 6.53 %. Serum samples of cervical cancer patients and healthy subjects were analyzed via the platform and the accuracy of the detection results was verified by qRT-PCR, revealing that SERS results and qRT-PCR results have high homogeneity. Thus, the platform can serve as a potential tool for clinical diagnosis of cervical cancer.

Integrated pretreatment diffusion kurtosis imaging and serum squamous cell carcinoma antigen levels: a biomarker strategy for early assessment of radiotherapy outcomes in cervical cancer.

OBJECTIVE: This study aims to explore the utility of pretreatment DKI parameters and serum SCC-Ag in evaluating the early therapeutic response of cervical cancer to radiotherapy. MATERIALS AND METHODS: A total of 33 patients diagnosed with cervical cancer, including 31 cases of cervical squamous cell carcinoma and two cases of adenosquamous carcinoma, participated in the study. All patients underwent conventional MRI and DKI scans on a 3T magnetic resonance scanner before radiotherapy and after ten sessions of radiotherapy. The therapeutic response was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Patients were categorized into a response group (RG), comprising Complete Remission (CR) and Partial Remission (PR), and a non-response group (NRG), comprising Stable Disease (SD) and Progressive Disease (PD). LASSO was employed to select pretreatment DKI parameters, and ROC curves were generated for the selected parameters and serum SCC-Ag. RESULTS: Significant differences were observed in pretreatment MD, Da, Dr, MK, Ka, Kr, and SCC-Ag between the RG and NRG groups (P < 0.01). However, no significant differences were noted for FA and FAK (P = 0.441&0.928). The two selected parameters (MD and MK) demonstrated area under the curve (AUC), sensitivity, and specificity of 0.810, 0.769, 0.850 and 0.827, 0.846, 0.750, respectively. The combination of MD and MK exhibited an improved AUC of 0.901, sensitivity of 0.692, and specificity of 1.000, with a higher Youden index compared to the individual parameters. Conversely, the AUC, sensitivity, and specificity of the combination of MD, MK, and SCC-Ag were 0.852, 0.615, and 1.000, with a Youden index of 0.615. CONCLUSION: Pretreatment MD, MK, and SCC-Ag demonstrate potential clinical utility, with the combined application of MD and MK showing enhanced efficacy in assessing the early therapeutic response of cervical cancer to radiotherapy. The addition of SCC-Ag did not contribute further to the assessment efficacy.

Highly expressed circ_0000285 from serum and cervical exfoliated cells as a novel biomarker for the diagnosis of early stage-cervical cancer.

Circ_0000285 is reported to play an oncogenic role in the development of cervical cancer (CC). The aim of this research was to investigate the diagnostic power of circ_0000285 in CC. The expression of circ_0000285 in 116 healthy volunteers, 65 early-stage CC (ESCC) patients, and 87 locally advanced CC (LACC) patients was detected by qRT-PCR. The diagnostic values of circ_0000285 for CC and ESCC were evaluated by ROC curves analysis. The circ_0000285 expression was upregulated in serum and cervical exfoliated cells from preoperative CC patients compared to that of healthy volunteers. Increased circ_0000285 expression was found in preoperative LACC patients more than that in ESCC patients. The circ_0000285 expression was downregulated in serum from CC patients after surgery. The postoperative CC patients with high serum circ_0000285 expression was more prone to have a tumour relapse. High circ_0000285 expression was positively correlated with SCC-Ag level and HPV positive rate. The AUC of circ_0000285 for the diagnosis of CC and ESCC were 0.855 and 0.804, better than CA125 and SCC-Ag. When circ_0000285, CA125, SCC-Ag and HPV were combined, the AUC could reach 0.911 and 0.894. In summary, highly expressed circ_0000285 from serum and cervical exfoliated cells might be a promising diagnostic biomarker for ESCC.Impact statementWhat is already known on this subject? The CA125 and SCC-Ag have limitations in the diagnosis of ESCC. Recently, circRNAs have caused great attention and have been developing rapidly in clinical diagnosis of malignant tumours.What do the results of this study add? Highly expressed circ_0000285 from serum and cervical exfoliated cells might be used as a novel, non-invasive biomarker for the diagnosis of ESCC.What are the implications of these findings for clinical practice and/or further research? Circ_0000285 is superior to CA125 and SCC-Ag for the diagnosis of ESCC in clinical practice. The results help to supplement the shortcomings of traditional tumour markers and improve the diagnosis of ESCC.

Clinical Value of Serum miR-106a in the Diagnosis and Prognosis of Human Papillomavirus-Positive Cervical Cancer.

INTRODUCTION: Cervical cancer (CC) is a prevailing malignant tumor in women, mainly caused by human papillomavirus (HPV) infection. This study investigated miR-106a expression in the serum of HPV-positive CC patients and estimated its value in diagnosis and prognosis. METHODS: We enrolled 120 CC patients as study subjects, with another 80 healthy women as controls. Clinical baseline data and clinicopathological indexes including age, tumor size, differentiation degree, FIGO stage, lymph node metastasis, and squamous cell carcinoma antigen (SCC-Ag) were recorded. Serum miR-106a expression was measured using reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristic curve was employed to estimate the efficacy of miR-106a in diagnosing CC or HPV-positive CC. Under a 5-year follow-up, patient survival was recorded, and the impact of miR-106a on overall survival rate was analyzed by the Kaplan-Meier method. The logistic regression model was used to analyze whether miR-106a was an independent prognostic factor for HPV infection in CC patients. RESULTS: Serum miR-106a was upregulated in CC patients and the level >1.365 assisted the CC diagnosis. miR-106a expression in HPV-positive CC patients was elevated relative to HPV-negative CC patients, and serum miR-106a level >1.300 distinguishing HPV positive and HPV negative. HPV positivity was linked with tumor differentiation degree, FIGO stage, lymph node metastasis, and SCC-Ag in CC patients, but not with age and tumor size. High expression of miR-106a in HPV-positive CC patients increased the risk of poor prognosis, and miR-106a expression is an independent prognostic factor for HPV infection in CC patients. CONCLUSION: High expression of miR-106a assists in the diagnosis of HPV-positive CC and predicts poor prognosis.

Dosimetric parameters and absolute monocyte count can predict the prognosis of acute hematologic toxicity in cervical cancer patients undergoing concurrent chemotherapy and volumetric-modulated arc therapy.

PURPOSE: To explore clinical and dosimetric predictors of acute hematologic toxicity (HT) in cervical cancer patients treated with concurrent chemotherapy and volumetric-modulated arc therapy (VMAT). METHODS AND MATERIALS: We retrospectively reviewed the clinical data of 184 cervical cancer patients who had concurrent chemotherapy and VMAT. Hematological parameters were collected during the treatment period. The total pelvic bone (TPB) was delineated retrospectively for dose-volume calculations. To compare the differences between two groups, the normality test findings were used to run a paired-samples t-test or Wilcoxon signed-rank test. Pearson's correlation analysis or Spearman's correlation was used to testing the correlation between the two variables. Binary logistic regression analysis was used to analyze associations between HT and possible risk factors. The receiver operating characteristic curve(ROC) was used to evaluate the best cut-off point for dosimetric planning constraints. RESULTS: The nadir of absolute monocyte count (AMC) was found to be positively correlated with the nadir of absolute white blood cells (WBC) count (r = 0.5378, 95% CI 0.4227-0.6357, P < 0.0001) and the nadir of absolute neutrophil count(ANC) (r = 0.5000, 95% CI 0.3794-0.6039, P < 0.0001). The AMC decreased and increased before the ANC and WBC. In multivariate logistic regression analysis, the chemotherapy regimens and the TPB_V20 were independent risk factors for developing grade ≥ 3 HT. The optimal TPB_V20 cut-off value identified by ROC curves and the Youden test was 71% (AUC = 0.788; 95% CI 0.722-0.845; P value < 0.001). CONCLUSIONS: The changing trend of AMC can be used as an effective predictor for the timing and severity of the ANC/WBC nadirs and prophylactic G-CSF administration. Maintain TPB_V20 < 71% and selecting single-agent cisplatin or carboplatin could significantly reduce grade ≥ 3 HT in cervical cancer patients undergoing concurrent chemoradiotherapy.

Serum CCAT2 as a biomarker for adjuvant diagnosis and prognostic prediction of cervical cancer.

Growing evidence indicates that lncRNA colon cancer-associated transcript 2 (CCAT2) is associated with cancers. However, the clinical value of CCAT2 in cervical cancer (CC) remains unclear. In this study, serum CCAT2 level was detected by real-time quantitative PCR (RT-qPCR). Carbohydrate antigen 125 (CA125) and squamous-cell carcinoma antigen (SCC) were detected by electrochemiluminescence. A receiver operating characteristic (ROC) curve was utilized to estimate the diagnostic efficiency of CCAT2. Kaplan-Meier survival analysis and univariable and multivariable analyses were performed to assess the prognostic value of CCAT2. The relative expression level of CCAT2 in primary CC patients was significantly higher than that in cervical intraepithelial neoplasias (CIN) patients and healthy controls (both P < 0.001). CCAT2 relative expression was positively correlated with tumor Federation of Gynecology and Obstetrics (FIGO) stage, SCC-Ag and lymph node metastasis (LNM) (all P < 0.05). CCAT2 expression in recurrent/metastatic CC was significantly higher compared with primary CC (P < 0.0001) or operated CC (P < 0.0001) and during follow-up, CCAT2 expression was increased before surgery and decreased significantly after surgery (P < 0.0001). Furthermore, the overall survival rate of CC patients with high CCAT2 expression group markedly decreased as compared with that of low CCAT2 expression group (P = 0.026). Univariate analyses indicated that CCAT2 was a poor prognostic factor associated with overall survival (OS). Our study indicates that CCAT2 may be valuable in complementary diagnosis and monitoring of progression and prognosis of CC patients. Combined detection of CCAT2, CA125 and SCC can greatly improve the diagnostic efficiency of primary CC.

Prognostic value of tumor measurement parameters and SCC-Ag changes in patients with locally-advanced cervical cancer.

OBJECTIVE: To investigate the prognostic relevance of specific measurement parameters such as tumor diameter, tumor volume, tumor volume reduction rate (TVRR), and changes in the squamous cell carcinoma antigen (SCC-Ag) level in patients with locally-advanced cervical cancer (LACC) undergoing concurrent radiotherapy and chemotherapy. METHODS: This was a retrospective study of 203 patients with stage IIA-IVA cervical squamous cell carcinoma who were newly diagnosed at our hospital between January 2011 and March 2015. Clinical data and pre-and post-treatment imaging information were collected and each parameter was calculated using 3DSlicer software. The pre/post-treatment tumor diameter (TDpre/post), tumor volume (TVpre/post), SCC-Ag (SCCpre/post), and TVRR, SCC-Ag reduction rate (SCCRR) were analyzed and their prognostic relevance evaluated. RESULTS: The median follow-up was 69 months. The 5-year overall survival (OS) and disease progression-free survival (PFS) rates were 69.5% and 64.5%, respectively. On univariate analysis, TDpre/post, TVpre/post, TVRR, SCCpre/post and SCCRR showed significant association with OS and PFS (P < 0.05). On multivariate analysis, TDpre [Hazard ratio (HR) = 0.373, P = 0.028], TDpost (HR = 0.376, P = 0.003) and SCCpost (HR = 0.374, P = 0.001) were independent predictors of OS. TVRR (HR = 2.998, P < 0.001), SCCpre (HR = 0.563, P = 0.041), and SCCpost (HR = 0.253, P < 0.001) were independent predictors of PFS. Tumor measurement parameters showed a positive correlation with SCC-Ag (P < 0.05). CONCLUSION: TDpre/post, TVpre/post, TVRR, SCCpre/post, and SCCRR were prognostic factors in LACC. TDpre/post and SCCpost showed the most significant prognostic value. TVRR and SCCpre/post were closely related to disease progression. Further studies should investigate the correlation between measurement parameters of tumor and SCC-Ag.

Elevated serum expression of p53 and association of TP53 codon 72 polymorphisms with risk of cervical cancer in Bangladeshi women.

Differential expression of p53 has been reported in cervical cancer, primarily in tumor tissue biopsies. In this study, we examined the association of TP53 codon 47 and codon 72 polymorphisms and serum level expression of p53 in cervical cancer patients (n = 129) and healthy controls (n = 122). We found elevated levels of serum p53 protein levels in cervical cancer patients (p = 0.0442) compared to healthy controls. Moreover, we found higher levels of serum p53 in patients with grade-III tumor (p = 0.001) compared to healthy controls. Examination of SNPs showed TP53 Arg/Pro heterozygosity (adjusted OR = 2.126, 95% CI = 1.181-3.827, p = 0.012), Pro/Pro mutant homozygosity (adjusted OR = 3.564, 95% CI = 1.647-7.713, p = 0.001), along with the combined genotype (Arg/Pro+Pro/Pro) (adjusted OR 2.542, 95% CI = 1.517-4.260, p<0.001) significantly increases the risk of cervical cancer. Expression quantitative trait analysis revealed no significant association with protein expression. Our results represent for the first time the upregulation of serum p53 in cervical cancer in Bangladeshi women and supports the association of TP53 codon 72 polymorphisms with cervical cancer.