Prognostic Factor In Cervical Cancer Research Articles

FABP4 is an independent risk factor for lymph node metastasis and poor prognosis in patients with cervical cancer

BackgroundPelvic lymph node metastasis (LNM) is a crucial independent prognostic factor in cervical cancer (CCa) and serves as an indicator for radiation therapy as the primary or an adjuvant treatment option. However, preoperative diagnosis of LNM remains challenging. Thus, we aimed to identify biomarkers of LNM in patients with presumed early-stage CCa.MethodsThe differentially expressed genes (DEGs) between tumours with different lymph node statuses were identified by using The Cancer Genome Atlas database. Then, univariate Cox regression analysis and Kaplan–Meier analyses were utilized to screen overall survival (OS)-associated genes. Multivariate Cox analysis and logistical analysis were utilized to evaluate independent risk factors for OS and LNM, respectively. Subsequently, the protein level of fatty acid binding protein 4 (FABP4) was detected in normal cervical and CCa tissues by immunohistochemistry assays. EdU assays were performed to determine whether FABP4 altered the proliferation of cervical cancer cells. Wound healing and Transwell assays were conducted to explore the effects of FABP4 depletion on migratory and invasive abilities of cervical cancer cells. F-actin fluorescence staining were performed to investigate morphological change and Western blotting analyses were performed to determine epithelial mesenchymal transition-related marker expression and downstream signalling pathways.ResultsA total of 243 DEGs, including 55 upregulated and 188 downregulated DEGs, were found in CCa patients with LNM versus those without LNM. Among these, FABP4 was found to be closely associated with poor OS. Multivariate analysis uncovered that FABP4 was an independent risk factor for OS and LNM in patients with CCa. The immunohistochemical results verified dramatically increased FABP4 expression in CCa tissues compared to normal cervical epithelia and its association with poor OS and LNM. In vitro, The proliferation, migration and invasion of cervical cancer cells were significantly inhibited after knocking down of FABP4, which was accompanied by elevated expression of E-cadherin and downregulated expression of N-cadherin, Vimentin and p-AKT.ConclusionsFABP4 might be a promising biomarker of LNM and survival in patients with early-stage CCa and therefore could significantly contribute to the development of personalized prognosis prediction and therapy optimization.

Expression and prognosis of CDC45 in cervical cancer based on the GEO database.

Cervical cancer is one of the most common malignant tumors in women, and its morbidity and mortality are increasing year by year worldwide. Therefore, an urgent and challenging task is to identify potential biomarkers for cervical cancer. This study aims to identify the hub genes based on the GEO database and then validate their prognostic values in cervical cancer by multiple databases. By analysis, we obtained 83 co-expressed differential genes from the GEO database (GSE63514, GSE67522 and GSE39001). GO and KEGG enrichment analysis showed that these 83 co-expressed it mainly involved differential genes in DNA replication, cell division, cell cycle, etc.. The PPI network was constructed and top 10 genes with protein-protein interaction were selected. Then, we validated ten genes using some databases such as TCGA, GTEx and oncomine. Survival analysis demonstrated significant differences in CDC45, RFC4, TOP2A. Differential expression analysis showed that these genes were highly expressed in cervical cancer tissues. Furthermore, univariate and multivariate cox regression analysis indicated that CDC45 and clinical stage IV were independent prognostic factors for cervical cancer. In addition, the HPA database validated the protein expression level of CDC45 in cervical cancer. Further studies investigated the relationship between CDC45 and tumor-infiltrating immune cells via CIBERSORT. Finally, gene set enrichment analysis (GSEA) showed CDC45 related genes were mainly enriched in cell cycle, chromosome, catalytic activity acting on DNA, etc. These results suggested CDC45 may be a potential biomarker associated with the prognosis of cervical cancer.

The co-expression of CBX8 and PD-L1 and prognostic value in cervical cancer.

Chromobox homolog 8 (CBX8) plays an important role in the occurrence and development of various tumors, and is closely related to the prognosis of patients with cancer. However, the occurrence, development, and prognostic value of CBX8 in cervical cancer have not been reported yet.In this study, immunohistochemistry was used to detect the expression of CBX8 in cervical cancer tissues and the corresponding normal tissues adjacent to the tumor. Furthermore, the relationship between CBX8 and programmed death-ligand 1 (PD-L1) expression, clinicopathological characteristics, and prognosis of cervical cancer were explored, and the prognostic value of CBX8 in cervical cancer was clarified.In this study, the results of immunohistochemistry using tissue chips obtained from patients with cervical cancer showed that CBX8 was highly expressed in cervical cancer tissues, and its expression was proportional to the international federation of gynecology and obstetrics (FIGO) stage. Disease-free and overall survival of patients with high CBX8 expression in cervical cancer were significantly shorter than those of patients with low CBX8 expression. Thus, CBX8 was found to be an independent prognostic factor for patients with cervical cancer. In addition, CBX8 and PD-L1 co-expression model could better predict the prognosis of patients with cervical cancer, and its area under the receiver operating characteristic curve was similar to that of FIGO stage.CBX8 may be an independent prognostic factor for cervical cancer. Moreover, the CBX8 and PD-L1 co-expression model could predict the postoperative survival of patients with cervical cancer objectively and reliably, which will aid clinicians to shunt patients with cervical cancer based on the risk of death, develop a reasonable treatment plan, and provide personalized prognosis.

Perineural Invasion Should Be Regarded as an Intermediate-Risk Factor for Recurrence in Surgically Treated Cervical Cancer: A Propensity Score Matching Study.

Background Perineural invasion (PNI) is considered as a poor prognostic factor in cervical cancer, but there has been no postoperative adjuvant therapy for it, because whether it belongs to high- or intermediate-risk factors has not been determined, this study intends to provide evidences to solve this problem. Methods We conducted a retrospective analysis of cervical cancer patients who underwent radical surgery and be reported PNI from January 2012 to June 2017 at the Sun Yat-sen University Cancer Center. After 1 : 1 propensity score matching (PSM), a group of patients without PNI was matched according to the clinical pathological features. Postoperative pathological parameters and prognosis were evaluated between the PNI and the matched groups. Results 1836 patients were screened, of which 162 (8.8%) diagnosed as stages IB1 to IIB reported PNI. Comparing to the matched group, more PNI (+) patients had deep outer cervix stromal invasion, cervical tunica adventitia invasion, positive lymph nodes, and positive margins. Among patients without high-risk factors, PNI (+) patients had worse 3-year overall survival (90.8% vs. 98.1%, P = 0.02), PNI (+) patients with single intermediate-risk factor and PNI (-) patients who meet with SEDLIS criteria had similar progress free survival (P = 0.63) and overall survival (P = 0.63), even similar survival curves. Conclusion PNI is related to a worse overall survival among cervical cancer patients without high-risk factors and play the role as an intermediate-risk factor.

Radiomic models for lymph node metastasis prediction in cervical cancer: can we think beyond sentinel lymph node?

Liu and colleagues performed a retrospective study to validate a computed tomography (CT) scan-based radiomic model to detect lymph node metastasis in cervical cancer. The proposed model incorporating the arterial and venous phase CT-scan features represented a non-invasive method exhibiting high sensitivity in the prediction of lymph node metastasis. It is well established that lymph node metastasis is one of the most significant prognostic factors in cervical cancer. For this reason, management of cervical cancer is strictly related to lymph node status, with international guidelines recommending definitive chemo-radiation in case of metastatic lymph node. More and more evidence supports the use of sentinel lymph node in early-stage cervical cancer but its frozen section analysis may result in false negative results; in locally-advanced stages staging para-aortic lymphadenectomy is proposed by many Authors to tailor chemoradiotherapy treatment, with potential intra-and post-operative related complications. The use of a validated radiomic model able to predict lymph node metastases in radiologically normal lymph nodes may represent an essential tool to possibly spare lympadenectomy related morbidity.

How to predict para-aortic node involvement in advanced cervical cancer? Development of a predictive score. A FRANCOGYN study

IntroductionNode involvement is one of the main prognostic factors for cervical cancer. Para-aortic lymph node (PALN) assessment is crucial for treating advanced cervical cancer, to define irradiation fields. Objective of this study was to develop a score predicting para-aortic lymph node involvement in patients with advanced cervical cancer. Patients and methodWe performed a multicenter, retrospective, study on 9 French centers from 2000 to 2015, including patients with advanced squamous cell cervix carcinoma who had PALN status assessed by imaging and/or by surgery. Factors associated with a risk of PALN involvement were determined by univariate and multivariate analysis using a logistic regression model. A score was then developed and validated. ResultsA total of 1446 patients treated for cervical cancer were included. Of these, 498 had an advanced squamous cell cervical cancer. Ninety-one patients (18.3%) had positive PALN. After univariate and multivariate analysis, tumor size on pelvic MRI, initial SCC, and suspected pelvic node involvement on PET-CT were included in our score. This model allowed the population to be divided into 3 risk groups. Area under the ROC curve of the score was 0.81 (95%CI = 0.72–0.90). In the low-risk group, 9% (28/287) had PALN involvement, whereas in the high-risk group, 43% (22/51) had PALN involvement. ConclusionWe developed a simple score predicting PALN involvement in advanced cervical cancers. Three risk groups can be defined, and patients considered to be at low risk may avoid para-aortic staging as well as extensive field irradiation.

The Importance of Clinical Examination under General Anesthesia: Improving Parametrial Assessment in Cervical Cancer Patients.

Simple SummaryIn most cases, the treatment strategy (radiation or surgery) in cervical cancer patients depends on whether the parametrium shows tumor involvement. Traditionally, clinical pelvic examination under general anesthesia (EUA) has been used to determine whether tumor spread into the parametrium is present. During the recent decade, however, magnetic resonance imaging (MRI) has been increasingly used to determine whether parametrial tumor extension is present, and several studies have indicated that MRI might be superior to EUA. In this study, we demonstrate that EUA still plays an important role in pre-therapeutic evaluation of cervical cancer patients, and that display of MR images in the operating room (augmented EUA) achieves superior results in predicting parametrial tumor spread when comparted to MRI alone, especially in larger tumors. Best predictive results were observed in cases when radiologists and gynecological oncologists agreed on parametrial status, highlighting the importance of interdisciplinary patient assessment.Background: Parametrial tumor involvement is an important prognostic factor in cervical cancer and is used to guide management. Here, we investigate the diagnostic value of clinical examination under general anesthesia (EUA) and magnetic resonance imaging (MRI) in determining parametrial tumor spread. Methods: Post-operative pathological findings of 400 patients with primary cervical cancer were compared to the respective MRI data and the results from EUA. The gynecological oncologist had access to the MR images during clinical assessment (augmented EUA, aEUA). Results: Pathologically proven parametrial tumor invasion was present in 165 (41%) patients. aEUA exhibited a higher accuracy than MRI alone (83% vs. 76%; McNemar’s odds ratio [OR] = 2.0, 95%CI 1.25–3.27, p = 0.003). Although accuracy was not affected by tumor size in aEUA, MRI was associated with a lower accuracy in tumors ≥2.5 cm (OR for a correct diagnosis compared to smaller tumors 0.22, p < 0.001). There was also a decrease in specificity when evaluating parametrial invasion by MRI in tumors ≥2.5 cm in diameter (p < 0.0001) compared to smaller tumors (< 2.5 cm). Body mass index had no influence on performance of either method. Conclusions: aEUA has the potential to increase the diagnostic accuracy of MRI in determining parametrial tumor involvement in cervical cancer patients.

PD-1 Expression Status on CD8+ Tumour Infiltrating Lymphocytes Associates With Survival in Cervical Cancer.

Despite the expansion of PD-1 checkpoint blockade to multiple types of cancer, whether the programmed cell death 1 (PD-1) expression status on CD8+ tumour infiltrating lymphocytes (TILs) could be a prognostic factor in cervical cancer is still unclear. In this study, we performed ex vivo phenotypic analysis of PD-1 expression on CD8+ TILs by flow cytometry from 47 treatment-naïve cervical cancer patients. With a median follow-up of 26.1 months (95% confidence interval [CI], 24-28.2 months), we then linked the quantitative cellular expression results to progression-free survival and overall survival. Based on the intensity of PD-1 expression, we further categorised the cervical cancer patients into PD-1high expressers (29.8%, 14/47) and PD-1low expressers (70.2%, 33/47). Multivariate analysis revealed that PD-1high expressers are correlated with early recurrence (HR, 5.91; 95% CI, 1.03-33.82; P= 0.046). Univariate analysis also demonstrated that PD-1high expressers are associated with poor overall survival in cervical cancer (HR, 5.365; 95% CI, 1.55-18.6; P=0.008). Moreover, our study also demonstrated that CD8+/CD4+ TIL ratio and HPV infection status are risk factors for early relapse and mortality in cervical cancer patients. In conclusion, this study confirms that PD-1 expression status is an independent prognostic factor for progression free survival in cervical cancer. These findings could be important in predicting the relapse of cervical cancer as a cellular diagnosis method and could be important knowledge for the selection of prospective PD-1 blockade candidates.

The Clinical Significance and Biological Function of PCDH7 in Cervical Cancer

PurposeCervical cancer is a common cancerous tumor in women that is prone to recurrence and metastasis. Recently, many people have explored the role of protocadherin 7 (PCDH7) in cancer and found that PCDH7 is abnormally expressed in many cancers. The purpose of this study is to explore the expression and mechanism of PCDH7 in cervical cancer and evaluate its clinical prognostic significance.Materials and MethodsThe expression of PCDH7 in cervical cancer and cells was measured by qRT-PCR. The relationship between PCDH7 expression and the clinical prognosis was calculated using the Kaplan–Meier method and Cox regression analyses. Effects of PCDH7 on cancer cell proliferation, migration, and invasion were studied by MTT assay and transwell assays.ResultsThe expression of PCDH7 in cervical cancer tissues and cell lines was notably downregulated compared with the corresponding control. Low PCDH7 expression was associated with a low survival rate. PCDH7 expression was correlated with lymph node metastasis, cell differentiation, and FIGO staging. PCDH7 can be used as an independent prognostic factor for cervical cancer. Up-regulation of PCDH7 significantly inhibited the proliferation ability, migration potential, and invasion capacity of cancer cells.ConclusionPCDH7 may be used as a prognostic biomarker for cervical cancer patients.

Strategies for the Treatment of Cervical Cancer with Bulky Pelvic Lymph Nodes: An Overview of the Current Evidence.

Cervical cancer commonly metastasizes first to the pelvic lymph nodes and then subsequently spreads to distant organs, making lymph node metastases the most significant prognostic factor in cervical cancer, and the strategy for its treatment directly influences prognosis. This review focuses on the treatment strategies for cases of cervical cancer with bulky pelvic lymph nodes. Concurrent chemoradiotherapy is the standard treatment modality for patients with pelvic lymph node metastases, but it is inadequate for bulky pelvic lymph nodes. Accordingly, surgical resection of the bulky lymph nodes has been attempted, and its therapeutic significance has been reported. If the bulky lymph nodes are unresectable, definitive concurrent chemoradiotherapy is performed. If it yields an inadequate degree of lymph node shrinkage, boosted radiation should be considered. The addition of chemotherapy after concurrent chemoradiotherapy has also been reported to be effective in patients with lymph node metastases and is currently being evaluated in clinical trials.

Pre-treatment Lean Body Mass on Disease Free Survival in Cervical Cancer Patients

To study if pre-treatment sarcopenia is one of the prognostic factors in cervical cancer. This study was a retrospective study in a single institute. Two hundred fifty-two cervical cancer patients during January 2012 to January 2017 were enrolled. Pre- treatment lean body mass was measured by using the computed tomography (CT) simulation images. The abdominal muscle area measurement was contoured at the L3 vertebral level. It was identified and quantified by using the Hounsfield unit (HU) thresholds (–29 to +150). The L3 region contains psoas, paraspinal muscles (erector spinae, quadratus lumborum), and abdominal wall muscles (transversus abdominus, external and internal obliques, rectus abdominus). The cut-off value of sarcopenia using Prado et al’s criteria was less than 38.5 cm2/m2 in women. Two hundred fifty-two cervical cancer patients with the mean age of 54.68 years old (95% CI 53.14 – 56.23). According to FIGO stage in 2018, the cervical cancer patients in stage I, II, IIB, IIIA, IIIB, IIIC1, IIIC2, IVA were 20 (7.94%), 97 (38.49%), 130 (51.59%) and 5 (1.98%) patients, respectively. Two hundred thirty-nine (94.84%) patients were treated by concurrent chemoradiation. Cisplatin weekly protocol was the most common regimen in chemoradiation therapy. One hundred and twenty-one (48.41%) cervical cancer patients had pre-treatment sarcopenia. The median progression-free survival (PFS) and overall survival (OS) of the patients were 38.6 and 44.8 months, respectively. The PFS and OS rates were not different in normal and sarcopenia group. We conclude that pre-treatment sarcopenia in cervical cancer patient is not impact in progression free survival and overall survival.

Hyperthermia Combined with Concurrent Radiochemotherapy for 373 Patients with Cervical Cancer Stage IB-IV

Hyperthermia (HT) is a commonly used approach in tumor patients, but the efficacy was still uncertain on cervical cancer (CC) treatment. This study was to evaluate if HT combined with concurrent radiochemotherapy (RCT) could render a better survival in CC patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB-IV, and did not increase treatment related toxicity. This study was conducted between 2009 and 2013 in CC patients. Patient eligibility criteria included: (1) age between 25-70 years old; (2) Karnofsky ≥ 70; (3) FIGO stages IB-IV; (4) no prior RT, CT or surgery; (5) histologically confirmed cervical squamous carcinoma; (6) no RT and CT contraindications, no HT contraindications (no cardiac pacemaker, no body metal); (7) normal blood routine, liver and renal function, no vital organ function failure; (8) no double primary cancer (no malignancy except cervical cancer). Patients were randomly assigned into two treatment groups according to a computer-generated random number list: RCT and RCT+HT (RCHT). All patients were treated with external beam radiotherapy (EBRT), 1.8–2.0Gy/fraction per day, 5 days per week, to a total dose of 50.4 or 50Gy. A High-Dose-Rate intracavitary brachytherapy (HDRICB) application delivering a further dose of 5Gy/fraction, 4 or 5 fractions, twice every week, to a total dose of 20∼25Gy to point A. One week after the first EBRT, all patients were treated with cisplatin (PDD) and 5-fluorouracil (5-Fu) regimen (PF): PDD 30 mg/m2, d1-3; 5-Fu 350mg/m2, d1-5. HT was delivered after PF regimen in RCHT group using Radio Frequency HT machine. Temperature was controlled above average 40.5°C (range from 39.5∼41.5°C) for 60 minutes, twice a week, to a total of 6 fractions. Primary end points were 5-year overall survival (OS) and late toxicity. Secondary end points included local-regional relapse (LRFS) and acute toxicity. Analysis was done by per protocol approach. 373 patients completed treatment and were analyzed. 5-year overall survival (OS) in RCHT group (81.9%) was better than that in RCT group (72.3%) and the log-rank test showed statistically significant difference (p = 0.040). Univariate and multivariate COX regression analysis for 5-year OS showed statistically significant difference (p = 0.043, p = 0.045, respectively). 5-year local relapse-free survival (LRFS) in RCHT (86.8%) was also better than that in RCT (82.7%), but the difference was not significant. Acute or late toxicity was not significantly different between two groups. Advanced FIGO stage and larger tumor size showed higher risk of death and relatively poor prognosis in univariate and multivariate analysis. HT combined to RCT yielded a better 5-year OS in CC without increasing treatment related toxicity. Therefore, hyperthermia will be one of the most effective additional treatments. FIGO stage and tumor size were independent prognostic factors in CC.

Connecting METTL3 and intratumoural CD33+ MDSCs in predicting clinical outcome in cervical cancer

BackgroundMethyltransferase-like 3 (METTL3) is a member of the m6A methyltransferase family and acts as an oncogene in cancers. Recent studies suggest that host innate immunity is regulated by the enzymes controlling m6A epitranscriptomic changes. Here, we aim to explore the associations between the levels of METTL3 and CD33+ myeloid-derived suppressor cells (MDSCs) in tumour tissues and the survival of patients with cervical cancer (CC).MethodsSpecimens of paraffin embedded tumour from 197 CC patients were collected. The expression levels of METTL3 and CD33 were measured by immunohistochemical (IHC) staining. The clinical associations of the IHC variants were analysed by Pearson’s or Spearman’s chi-square tests. Overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan–Meier method and log-rank test. Hazard ratios (HRs) and independent significance were obtained via Cox proportional hazards models for multivariate analyses. METTL3 in CD33+ cells or CC-derived cells was knocked down by METTL3-specific siRNA, and MDSC induction in vitro was performed in a co-culture system in the presence of METTL3-siRNA and METTL3-knockdown-CC-derived cells compared with that of the corresponding controls.ResultsWe found that tumour tissues displayed increased levels of METTL3 and CD33+ MDSCs compared with tumour-adjacent tissues from the same CC patients. Importantly, METTL3 expression was positively related to the density of CD33+ cells in tumour tissues (P = 0.011). We further found that the direct CD33+CD11b+HLA-DR− MDSC induction and tumour-derived MDSC induction in vitro were decreased in the absence of METTL3. The level of METTL3 in tumour microenvironments was significantly related to advanced tumour stage. The levels of METTL3 and CD33+ MDSCs in tumour tissues were notably associated with reduced DFS or OS. Cox model analysis revealed that the level of METTL3 in tumour cells was an independent factor for patient survival, specifically for DFS (HR = 3.157, P = 0.022) and OS (HR = 3.271, P = 0.012), while the CD33+ MDSC number was an independent predictor for DFS (HR: 3.958, P = 0.031). Interestingly, in patients with advanced-disease stages (II–IV), METTL3 in tumour cells was an independent factor for DFS (HR = 6.725, P = 0.010) and OS (HR = 5.140, P = 0.021), while CD33+ MDSC density was an independent factor for OS (HR = 8.802, P = 0.037).ConclusionOur findings suggest that CD33+ MDSC expansion is linked to high levels of METTL3 and that METTL3 and CD33+ MDSCs are independent prognostic factors in CC.

A 70-Gene Signature for Predicting Treatment Outcome in Advanced-Stage Cervical Cancer

Cervical cancer is the fourth most common cancer in women worldwide. The current approaches still have limitations in predicting the therapy outcome of each individual because of cancer heterogeneity. The goal of this study was to establish a gene expression signature that could help when choosing the right therapeutic method for the treatment of advanced-stage cervical cancer. The 666 patients were collected from four independent datasets. The 70-gene expression signature was established using univariate Cox proportional hazard regression analysis. The 70-gene signature was significantly different between low- and high-risk groups in the training dataset (p = 4.24e−6) and in the combined three validation datasets (p = 4.37e−3). Treatment of advanced-stage cancer patients in the high-risk group with molecular-targeted therapy combined with chemoradiotherapy yielded a better survival rate than with only chemoradiotherapy (p = 0.0746). However, treatment of the patients in the low-risk group with the combined therapy resulted in significantly lower survival (p = 0.00283). Functional classification of 70 genes revealed involvement of the angiogenesis pathway, specifically phosphatidylinositol 3-kinase signaling (p = 0.040), extracellular matrix organization (p = 0.0452), and cell adhesion (p = 0.011). The 70-gene signature could predict the prognosis and indicate an optimal therapeutic modality in molecular-targeted therapy or chemotherapy for advanced-stage cervical cancer.

HN1 promotes tumor associated lymphangiogenesis and lymph node metastasis via NF-κB signaling activation in cervical carcinoma

Lymph node metastasis (LNM) is a critical cause for disease progression and treatment failure in cervical cancer. However, the mechanism underlying cervical cancer LNM remains unclear. In this study, HN1 was found to be dramatically upregulated in cervical cancer and patients with higher HN1 expression are more likely to exhibit a higher rate of LNM and lower survival rate. Univariate and multivariate Cox-regression analyses showed that HN1 is an independent prognostic factor in cervical cancer. Meanwhile, HN1 promotes lymphangiogenesis of cervical cancer in vitro. The in vivo experiment also indicates that HN1 enhances LNM in cervical cancer. Furthermore, we also found that HN1 activated the NF-κB signaling pathway to enhance the expression of downstream genes. Taken together, our study suggests that HN1 plays a crucial role in promoting LNM and acts as a prognostic biomarker in cervical cancer.

Prediction of early response to concurrent chemoradiotherapy in cervical cancer: Value of multi-parameter MRI combined with clinical prognostic factors

PurposeThis study aimed to investigate the prediction of early response to concurrent chemoradiotherapy (CCRT) through a combination of pretreatment multi-parametric magnetic resonance imaging (MRI) with clinical prognostic factors (CPF) in cervical cancer patients. MethodsEighty-five patients with pathologically confirmed cervical cancer underwent conventional MRI, intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI), and dynamic contrast-enhanced MRI (DCE-MRI) before CCRT. The patients were divided into non- and residual tumor groups according to post-treatment MRI. Univariable and multivariable analyses were performed to pretreatment MRI parameters and CPF between the two groups, and optimal thresholds and predictive performance for post-treatment residual tumor occurrence were estimated by drawing the receiver operating characteristic (ROC) curve. ResultsThere were 52 patients in non- and 33 in residual group. The residual group showed a lower perfusion fraction (f) value and volume transfer constant (Ktrans) value, a higher apparent diffusion coefficient (ADC) value, diffusion coefficient (D) value and volume fraction of extravascular extracellular space (Ve) value, and a higher stage than the non-residual tumor group (all P < .05). D, Ktrans, Ve and stage were independent prognostic factors. The combination of D, Ktrans and Ve improved the diagnostic performance compared with individual MRI parameters. A further combination of these three MRI parameters with stage exhibited the highest predictive performance. ConclusionsPretreatment D, Ktrans, Ve and stage were independent prognostic factors for cervical cancer. The predictive capacity of multi-parametric MRI was superior to individual MRI parameters. The combination of multi-parametric MRI with CPF further improved the predictive performance.

Analysis of the Role and Regulatory Mechanism of hsa-miR-504 in Cervical Cancer Based on The Cancer Genome Atlas Database.

Objective: This study investigated the expression and clinical value of hsa-miR-504 in cervical cancer and its possible mechanism of regulating the progress of cervical cancer. Methods: The expression of microRNAs (miRNAs) in cervical cancer was analyzed on The Cancer Genome Atlas (TCGA) database. The correlation between differentially expressed miRNAs and overall survival (OS) of cervical cancer patients was analyzed by Kaplan-Meier method. The target genes regulated downstream by hsa-miR-504 were predicted by miRWalk 2.0 and analyzed by Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) after differential screening. Univariate and multivariate Cox regressions were performed to screen the prognosis-related target genes. Results: There were 82 differentially expressed miRNAs between cervical cancer and noncancerous tissues in TCGA database (fold change >2, p < 0.05). Among them, nine miRNAs, including hsa-miR-504, were significantly correlated with OS in cervical cancer patients. Hsa-miR-504 was downregulated in cervical cancer, and low hsa-miR-504 expression was associated with poor prognosis. There were 2670 target genes of hsa-miR-504, and 240 target genes were further confirmed to be upregulated by TCGA database (fold change >2, p < 0.05). GO and KEGG showed that the upregulated target genes were mainly enriched in cell cycle, DNA replication, p53 signaling pathway, and so on. Kaplan-Meier survival analysis showed that 21 target genes were associated with OS in cervical cancer patients (p < 0.05). Univariate and multivariate Cox regression analysis showed that five genes were independent prognostic factors in cervical cancer. Conclusion: The low expression of hsa-miR-504 was closely related to the occurrence and development of cervical cancer, and hsa-miR-504 might be a potential molecular marker for favorable prognosis in cervical cancer. Cell cycle, DNA replication, and p53 signaling pathway were important mechanisms of downregulated hsa-miR-504 involved in the occurrence and development of cervical cancer.

Differences in Treatment Outcomes and Prognosis between Elderly and Younger Patients Receiving Definitive Radiotherapy for Cervical Cancer.

The aim was to compare the clinical outcomes and prognostic factors of cervical cancer between elderly and younger women, and to explore which treatment strategy is more appropriate for elderly patients. We retrospectively reviewed patients with cervical cancer receiving definitive radiotherapy (RT) between 2007 and 2016, and divided them into two age groups: age < 70 vs. age ≥ 70. The clinical outcomes were compared between the two age groups. The median follow-up was 32.2 months. A total of 123 patients were eligible, 83 patients in group 1 (age < 70), and 40 patients in group 2 (age ≥ 70). Patients in group 2 received less intracavitary brachytherapy (ICRT) application, less total RT dose, and less concurrent chemoradiotherapy (CCRT), and tended to have more limited external beam radiotherapy (EBRT) volume. The treatment outcomes between the age groups revealed significant differences in 5-year overall survival (OS), but no differences in 5-year cancer-specific survival (CSS), 66.2% vs. 64.5%, and other loco-regional control. In multivariate analyses for all patients, the performance status, pathology with squamous cell carcinoma (SCC), International Federation of Gynecology and Obstetrics (FIGO) stage, and ICRT application were prognostic factors of CSS. The elderly patients with cervical cancer had comparable CSS and loco-regional control rates, despite receiving less comprehensive treatment. Conservative treatment strategies with RT alone could be appropriate for patients aged ≥ 70 y/o, especially for those with favorable stages or histopathology.

Correlation of PR and ER expression in tumors in various growth patterns of cervical cancer as a prognostic factor.

e18031 Background: Cervical cancer is the fourth leading cause of cancer deaths among women worldwide. Since the uterus has receptors through which hormonal effects are realized, studies on the tissue receptor apparatus for estrogen and progesterone are relevant. The purpose of the study was to evaluate the correlation of PR and ER expression as a prognostic factor in cervical cancer. Methods: The study included 60 patients aged 28-65 years diagnosed with cervical cancer. Patients were divided into two groups: group 1 – endophytic pattern of tumor growth (n = 30), group 2 – exophytic pattern (n = 30). Eligibility criteria included morphologically confirmed squamous cell carcinoma of the cervix T1b-2aN0M0, stage I-II. Rabbit monoclonal antibodies for ER (Thermo scientific) and PR (Cell Marque) with the Reveal Polyvalent HRP-DAB Detection System were used for the IHC analysis. Statisical analysis of the results was performed with the Statistica 10 program (StatSoft Inc., USA). Results: The average expression of the ER marker was 5.4±3.03% for group 1 (endophytic tumors) and 13.9±8.2% for group 2 (exophytic tumors). The average PR expression was 0.5±0.3% and 1.6±1.1%, respectively. The maximal accumulation of both PR and ER in the nuclei of tumor cells was registered in patients of group 2, being 3.2 times (p = 0.931) and 2.6 times (p = 0.815) higher than in group 1, respectively. However, the difference was not statistically significant (the Mann-Whitney test, p &gt; 0.05). The Spearman rank correlation test did not show statistically significant correlation between the groups and the markers (r = -0.218, p = 0.338). Statistically significant correlation was observed only in the group with exophytic pattern of tumor growth (r = 0.786, p &lt; 0.01). Conclusions: The IHC analysis revealed a tendency to an increase in the expression of PR and ER in patients with exophytic tumors. However, the correlation between the expression of these indicators cannot be considered as a predictive factor in cervical cancer.

Functional implications of miR-145/RCAN3 axis in the progression of cervical cancer

Cervical cancer, as the second leading cause of death in women malignant tumor, is not optimistic about survival rate and late recurrence rate. RCAN3 has been reported to function in a variety of diseases, but its relationship with cervical cancer has not been reported. This study aimed to investigate whether RCAN3 contributes to the development of cervical cancer and its mechanism. RCAN3 expression was analyzed in 306 cervical cancer tissues and 13 normal healthy tissues from TCGA and GTEX databases. Kaplan-Meier analysis and Cox regression analysis were carried out to assess the potential function of RCAN3. Subsequently, the upstream regulatory miRNA of RCAN3 was predicted by bioinformatics and confirmed using dual luciferase reporter assay. CCK-8, colony formation assay, transwell assay were used for functional analysis of miR-145/RCAN3 axis in vitro. The results showed that RCAN3 was highly expressed in cervical cancer tissues, leading to poor prognosis, and could be used as a prognostic factor for cervical cancer. MiR-145 directly targeted RCAN3, which was lowly expressed in cervical cancer tissues and cell lines, and the higher the miR-145 expression, the longer the survival time of patients. Finally, from the functional experiments results we can see that miR-145 can inhibit the proliferation, migration and invasion of cervical cancer cells, but overexpression of RCAN3 can reverse miR-145-mediated inhibition. To sum up, miR-145/RCAN3 axis may serve as a potential therapeutic target to regulate the progression of cervical cancer.