Glycolysis Induced by METTL14 Is Essential for Macrophage Phagocytosis and Phenotype in Cervical Cancer.

N 6-methyladenosine (m6A) is the most abundant mRNA modification in mammals and it plays a vital role in various biological processes. However, the roles of m6A on cervical cancer tumorigenesis, especially macrophages infiltrated in the tumor microenvironment of cervical cancer, are still unclear. We analyzed the abnormal m6A methylation in cervical cancer, using CaSki and THP-1 cell lines, that might influence macrophage polarization and/or function in the tumor microenvironment. In addition, C57BL/6J and BALB/c nude mice were used for validation in vivo. In this study, m6A methylated RNA immunoprecipitation sequencing analysis revealed the m6A profiles in cervical cancer. Then, we discovered that the high expression of METTL14 (methyltransferase 14, N6-adenosine-methyltransferase subunit) in cervical cancer tissues can promote the proportion of programmed cell death protein 1 (PD-1)-positive tumor-associated macrophages, which have an obstacle to devour tumor cells. Functionally, changes of METTL14 in cervical cancer inhibit the recognition and phagocytosis of macrophages to tumor cells. Mechanistically, the abnormality of METTL14 could target the glycolysis of tumors in vivo and vitro. Moreover, lactate acid produced by tumor glycolysis has an important role in the PD-1 expression of tumor-associated macrophages as a proinflammatory and immunosuppressive mediator. In this study, we revealed the effect of glycolysis regulated by METTL14 on the expression of PD-1 and phagocytosis of macrophages, which showed that METTL14 was a potential therapeutic target for treating advanced human cancers.

A Histopathologic Image Analysis for the Classification of Endocervical Adenocarcinoma Silva Patterns Depend on Weakly Supervised Deep Learning.

Twenty-five percent of cervical cancers are classified as endocervical adenocarcinomas (EACs), which comprise a highly heterogeneous group of tumors. A histopathologic risk stratification system known as the Silva pattern system was developed based on morphology. However, accurately classifying such patterns can be challenging. The study objective was to develop a deep learning pipeline (Silva3-AI) that automatically analyzes whole slide image-based histopathologic images and identifies Silva patterns with high accuracy. Initially, a total of 202 patients with EACs and histopathologic slides were obtained from Qilu Hospital of Shandong University for developing and internally testing the Silva3-AI model. Subsequently, an additional 161 patients and slides were collected from seven other medical centers for independent testing. The Silva3-AI model was developed using a vision transformer and recurrent neural network architecture, utilizing multi-magnification patches, and its performance was evaluated based on a class-specific area under the receiver-operating characteristic curve. Silva3-AI achieved a class-specific area under the receiver-operating characteristic curve of 0.947 for Silva A, 0.908 for Silva B, and 0.947 for Silva C on the independent test set. Notably, the performance of Silva3-AI was consistent with that of professional pathologists with 10 years' diagnostic experience. Furthermore, the visualization of prediction heatmaps facilitated the identification of tumor microenvironment heterogeneity, which is known to contribute to variations in Silva patterns.

APLN promotes the proliferation, migration, and glycolysis of cervical cancer through the PI3K/AKT/mTOR pathway.

Apelin (APLN) is an endogenous ligand of the G protein-coupled receptor APJ (APLNR). APLN has been implicated in the development of multiple tumours. Herein, we determined the effect of APLN on the biological behaviour and underlying mechanisms of cervical cancer. The expression and survival curves of APLN were determined using Gene Expression Profiling Interactive Analysis. The cellular functions of APLN were detected using CCK-8, clone formation, EdU, Transwell assays, flow cytometry, and seahorse metabolic analysis. The underlying mechanisms were elucidated using gene set enrichment analysis and Western blotting. APLN was upregulated in the samples of patients with cervical cancer and is associated with poor prognosis. APLN knockdown decreased the proliferation, migration, and glycolysis of cervical cancer cells. The opposite results were observed when APLN was overexpressed. Mechanistically, we determined that APLN was critical for activating the PI3K/AKT/mTOR pathway via APLNR. APLN receptor inhibitor ML221 reversed the effect of APLN overexpression on cervical cancer cells. Treatment with LY294002, the PI3K inhibitor, drastically reversed the oncological behaviour of APLN-overexpressing C-33A cells. APLN promoted the proliferation, migration, and glycolysis of cervical cancer cells via the PI3K/AKT/mTOR pathway.

Development and validation of a deep learning survival model for cervical adenocarcinoma patients.

BACKGROUND: The aim was to develop a personalized survival prediction deep learning model for cervical adenocarcinoma patients and process personalized survival prediction. METHODS: A total of 2501 cervical adenocarcinoma patients from the surveillance, epidemiology and end results database and 220 patients from Qilu hospital were enrolled in this study. We created our deep learning (DL) model to manipulate the data and evaluated its performance against four other competitive models. We tried to demonstrate a new grouping system oriented by survival outcomes and process personalized survival prediction by using our DL model. RESULTS: The DL model reached 0.878 c-index and 0.09 Brier score in the test set, which was better than the other four models. In the external test set, our model achieved a 0.80 c-index and 0.13 Brier score. Thus, we developed prognosis-oriented risk grouping for patients according to risk scores computed by our DL model. Notable differences among groupings were observed. In addition, a personalized survival prediction system based on our risk-scoring grouping was developed. CONCLUSIONS: We developed a deep neural network model for cervical adenocarcinoma patients. The performance of this model proved to be superior to other models. The results of external validation supported the possibility that the model can be used in clinical work. Finally, our survival grouping and personalized prediction system provided more accurate prognostic information for patients than traditional FIGO stages.

New mechanisms and biomarkers of lymph node metastasis in cervical cancer: reflections from plasma proteomics.

OBJECTIVE: Lymph node metastasis (LNM) and lymphatic vasculature space infiltration (LVSI) in cervical cancer patients indicate a poor prognosis, but satisfactory methods for diagnosing these phenotypes are lacking. This study aimed to find new effective plasma biomarkers of LNM and LVSI as well as possible mechanisms underlying LNM and LVSI through data-independent acquisition (DIA) proteome sequencing. METHODS: A total of 20 cervical cancer plasma samples, including 7 LNM-/LVSI-(NC), 4 LNM-/LVSI + (LVSI) and 9 LNM + /LVSI + (LNM) samples from a cohort, were subjected to DIA to identify differentially expressed proteins (DEPs) for LVSI and LNM. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for DEP functional annotation. Protein-protein interaction (PPI) and weighted gene coexpression network analysis (WGCNA) were used to detect new effective plasma biomarkers and possible mechanisms. RESULTS: A total of 79 DEPs were identified in the cohort. GO and KEGG analyses showed that DEPs were mainly enriched in the complement and coagulation pathway, lipid and atherosclerosis pathway, HIF-1 signal transduction pathway and phagosome and autophagy. WGCNA showed that the enrichment of the green module differed greatly between groups. Six interesting core DEPs (SPARC, HPX, VCAM1, TFRC, ERN1 and APMAP) were confirmed to be potential plasma diagnostic markers for LVSI and LNM in cervical cancer patients. CONCLUSION: Proteomic signatures developed in this study reflected the potential plasma diagnostic markers and new possible pathogenesis mechanisms in the LVSI and LNM of cervical cancer.

Effect of direct surgical treatment in pregnancy-related uterine arteriovenous malformation.

BACKGROUND: Uterine arteriovenous malformation (UAVM) is a relatively rare but potentially life-threatening situations abnormal vascular connections between the uterine arterial and venous systems. Lack of recognized guidelines and clinic experience, there is a lot of clinic problems about diagnosis and treatment. By analyzing the clinical data of patients with pregnancy-related UAVM, we aim to confirm the safety of direct surgeries and the benefit of pretreatment (uterine artery embolization or medical therapy) before surgery, and to explore more optimal therapies for patients with pregnancy-related UAVM. METHODS: A total of 106 patients in Qilu Hospital of Shandong University from January 2011 to December 2021 diagnosed of pregnancy-related UAVM were involved in this study. Depending on whether preoperative intervention was performed, the patients were divided into direct surgery group and pretreatment group (uterine artery embolization or medical management). Clinical characteristics, operative related factors and prognosis were analyzed. RESULTS: The most common symptom of pregnancy-related UAVM was vaginal bleeding (82.5%), which could also be accompanied by abdominal pain. Pretreatments (uterine artery embolization or medical therapy) had no obvious benefit to the subsequent surgeries, but increased the hospital stay and hospital cost. Direct surgery group had satisfactory success rate and prognosis compared to pretreatment group. CONCLUSION: For pregnancy-related UAVM, direct surgery has good effects and high safety with shorter hospital stays and less hospital cost. What is more, without uterine artery embolization and other medical therapy, patients could remain better fertility in future.

Analysis of prognostic factors for cervical mucinous adenocarcinoma and establishment and validation a nomogram: a SEER-based study.

Up to now, there are no relevant studies on prognostic factors of cervical mucinous adenocarcinoma. Therefore, we explored the prognostic factors for cervical mucinous adenocarcinoma, and established and validated the prognostic model using the SEER database. We selected the independent factors through univariate and multivariate analyses. LASSO regression analysis was conducted to identify potential risk factors. In conjunction with LASSO and multivariate analysis, the nomogram incorporated three variables, including age, tumour size, and AJCC stage for OS. The c-index was 0.794 and 0.831 in development and validated cohorts, indicating that this prediction model showed adequate discriminative ability in the development cohort. Besides, calibration curves showed good concordance for the development cohort, as well as the validation cohort. We constructed a first-of-its-kind nomogram to predict cervical mucinous adenocarcinomas OS and it showed better performance than AJCC and FIGO stages. Patients with cervical mucinous adenocarcinoma might benefit from using this model to develop tailored treatments.IMPACT STATEMENTWhat is already known on this subject? Cervical cancer has a variety of pathological types. The biological behaviour of each type is different, and the prognosis is quite different.What do the results of this study add? We analysed and explored the relevant factors affecting the prognosis of cervical mucinous adenocarcinoma.What are the implications of these findings for clinical practice and/or further research? Through the analysis of the SEER dataset, the prognostic factors affecting cervical mucinous adenocarcinoma were identified, and the first predictive model was created to predict the prognosis to help doctors develop individualised treatment plans and follow-up plans.

Comparison of different treatment strategies in the management of endogenic caesarean scar pregnancy: a multicentre retrospective study.

BACKGROUND: The aim of this study was to evaluate the effectiveness and safety of different treatment strategies for endogenic caesarean scar pregnancy (CSP) patients. METHODS: According to Vial's standard, we defined endogenic-type CSP as (1) the gestational sac growing towards the uterine cavity and (2) a greater than 0.3 cm thickness of myometrial tissue at the caesarean scar. A total of 447 endogenic CSP patients out of 527 patients from 4 medical centres in China were enrolled in this study. A total of 120 patients were treated with methotrexate (MTX) followed by surgery, 106 received ultrasound-guided curettage directly and 221 received curettage combined with hysteroscopy. The clinical information and clinical outcomes of these patients were reviewed. Successful treatment was defined as (1) no additional treatment needed, (2) no retained mass of conception and (3) serum ß subunit of human chorionic gonadotropin (ß-hCG) level returning to a normal level within 4 weeks. The success rate was analysed based on these factors. RESULT: Among 447 patients, no significant difference was observed in baseline characteristics between groups except for foetal heartbeat. The success rate was significantly different (p<0.001) among the three groups. The highest success rate of 95.9% was noted in the hysteroscopy group, and the lowest success rate of 84.0% was noted in the curettage group. In addition, the MTX group reported the longest hospital stay and highest expenses, but the curettage group showed the shortest and lowest expenses, respectively. Nevertheless, no difference in blood loss was observed between the groups. CONCLUSION: The combination of curettage and hysteroscopy represents the most effective strategy. Pretreatment with MTX did not result in better clinical outcomes. Ultrasound-guided curettage directly should not be considered a first-line treatment choice for endogenic CSP patients.

hsa_circ_0000745 promotes cervical cancer by increasing cell proliferation, migration, and invasion.

Circular RNAs (circRNAs) participate in gene regulation and malignant tumor progression, including uterine cervical cancer (CC). In this study, the expression profile of circRNAs in CC was detected using circRNA microarrays. Then, we selected hsa_circ_0000745 for further examination from the significantly dysregulated circRNAs. Proliferation assays, Transwell assays, quantitative reverse transcription polymerase chain reaction, western blot analysis and tumorigenesis tests in vivo were used to validate the role of hsa_circ_0000745 in CC. hsa_circ_0000745 was upregulated in CC, and its level positively correlated with the level of its linear messenger RNA isoform. Patients with poorly differentiated tumors or vascular/lymphatic invasion presented higher expression of hsa_circ_0000745. The role of hsa_circ_0000745 was illuminated by knocking down hsa_circ_0000745 in CC cells, and the results revealed that reducing hsa_circ_0000745 inhibited cell proliferation, migration, and invasion in CC by upregulating E-cadherin (E-cad) expression. In summary, as a tumor promoter in CC, hsa_circ_0000745 enhances the cell's ability to proliferate, migrate, and invade by reducing the expression of E-cad. hsa_circ_0000745 is a candidate target for the treatment of CC in the clinic.

Distribution of cervical lesions in high-risk HPV (hr-HPV) positive women with ASC-US: a retrospective single-center study in China.

BACKGROUND: To investigate distributions of cervical lesions and factors associated with the severity of the cervical lesions in high-risk HPV (hr-HPV) positive women with atypical squamous cells of undetermined significance (ASC-US) cytology. METHODS: Clinical information of 250,000 women who underwent HPV and cytological test was collected from January 2012 to January 2019. The association between the severity of the cervical lesions and hr-HPV genotypes, hr-HPV viral load, and ages, were analyzed in hr-HPV-positive/ASC-US women. RESULTS: 3459 hr-HPV-positive/ASC-US women were enrolled in this study. Overall, 43.51% of women with ASC-US had normal histological results, 34.35% had high-grade squamous intraepithelial lesion (HSIL), and 1.30% had cervical cancer. The rate of HSIL or worse (HSIL+) in women with single HPV16 infection (63.09%) was the highest, followed by HPV33 (57.50%), HPV51 (36.11%), HPV58 (36.11%), HPV52 (28.28%), HPV18 (26.37%), HPV66 (19.35%), HPV39 (18.92%), HPV53 (15.00%), and HPV56 (8.51%). Detection rate of HSIL+ in low, intermediate and high viral-load groups were 15.87% (n = 30), 34.91% (n = 74) and 40.68% (n = 214) (Cochran-Armitage Trend test χ2 = 35.03, p < 0.0001). Compared with the 51-60-year-old group (21.65%), the women in ≤ 30 (40.52%), 31-40 (39.67%), and 41-50 (34.22%) year-old groups had significantly higher risk of HSIL+. The women in ≤ 51-60 (2.68%) and > 60 (3.41%) year-old groups were at increased risk for cervical cancer, compared with the ≤ 30-year-old group (0.61%). CONCLUSIONS: ASC-US women with HPV 16/18/33/51/52/58 single infection and multiple infections, as well as high HPV viral loads, have high risk of HSIL+.

Can neutrophil-to-lymphocyte and monocyte-to-lymphocyte ratios be useful markers for predicting missed abortion in the first trimester of pregnancy?

AIM: To explore whether neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) could predict missed abortion (MA) at 7-13 week's gestation. METHODS: A total of 363 women with a diagnosis of MA and 232 women with normal pregnancy at 7-13 week's gestation, who visited our hospital from June 2012 to May 2018 were retrospectively analyzed. At 7 week's gestation, total and differential leukocyte counts, NLR and MLR were compared between women with MA (n = 69) and normal controls (n = 53). The receiver operating characteristic curve was used to select the optimal indicator and its cut-off point. The role of the optimal indicator was further assessed at 8-13 week's gestation. RESULTS: The mean white blood cell counts, the mean neutrophil counts, the median monocyte counts, the mean NLR and the median MLR in women with MA were significantly lower than those in normal controls (P < 0.05, respectively).The neutrophil counts had the highest area under the curve (AUC) value of 0.772 (95% confidence interval 0.675-0.869) with a cut-off value of 4.870 × 109 /L, and the sensitivity was 72.46%, the specificity was 69.81%, positive predictive value was 75.76%, and negative predictive value was 66.07%. In addition, the neutrophil counts were also significantly lower in MA groups than those in normal controls at 8-13 week's gestation, and all had the highest AUC values. CONCLUSION: Neutrophil counts may predict MA in the first trimester of pregnancy, which may provide a promising marker to diagnose missed abortion as early as 7 week's gestation.

Negative roles of B7-H3 and B7-H4 in the microenvironment of cervical cancer.

Although persistent human papilloma virus (HPV) infection exerts a crucial influence on cervical carcinogenesis, other factors are also involved in its development, such as intraepithelial lesions and cervical cancer. B7-H3 and B7-H4, which have been reported to be co-regulatory ligands in the B7 family, had been found to be overexpressed in cervical cancer and correlated with adverse clinicopathological features and poor prognosis in our previous studies. In this study, we sought to explore the effects of B7-H3 and B7-H4 on the cervical microenvironment. Among several immune cytokines, interleukin-10 (IL-10) and transforming growth factor (TGF) ß1 stand out as important immunosuppressive factors. Our studies found that IL-10 expression increased with pathological change levels and significantly correlated with cervical cancer differentiation (P < 0.05). TGF-ß1 correlated with lymph node metastasis (LNM) (P < 0.01). Expression of B7-H3 and B7-H4 positively correlated with the expression of IL-10 and TGF-ß1. After co-culture, we found that overexpression of B7-H3 and B7-H4 in cervical cancer cell lines resulted in activation of the cell cycle and decreased apoptosis of U-937 cells. In addition, the contents of IL-10 and TGF-ß1, as well as their protein expression levels, increased in co-culture supernatants in U-937 cells, suggesting regulation by the p-JAK2/STAT3 pathway. The in vivo results demonstrated that with the increasing expression of B7-H3/B7-H4, the expression of IL-10 and TGF-ß1 also increased significantly. Overall, the expression of B7-H3 and B7-H4 favored an immunosuppressive microenvironment by promoting the production of IL-10 and TGF-ß1, thereby resulting in progression of cervical carcinogenesis.

A comparison of the prognosis between adenocarcinoma and squamous cell carcinoma in stage IB-IIA cervical cancer.

OBJECTIVE: To explore differences in prognosis between adenocarcinoma (AC) and squamous cell carcinoma (SCC) and to explore feasibility of ovarian preservation in stage IB-IIA cervical cancer (CC). MATERIALS AND METHODS: Medical records of 810 patients (682 SCC + 128 AC) with stage IB-IIA CC were reviewed. Clinical and pathological characters of the two groups were compared using the chi-squared test. Kaplan-Meier survival analysis was used in univariate analysis of prognostic factors. Multivariate analysis of prognostic factors was conducted by the Cox hazards regression model. RESULTS: The incidence of LVSI (lymphovascular space invasion) and poor cell differentiation in SCC patients was higher than that in AC patients (23.90% vs. 8.59%, P < 0.05; and 54.25% vs. 28.91%, P < 0.05). Results of univariate analysis showed that cell differentiation, clinical stage, lymph node metastasis (LNM), ovarian metastasis (OM), parametrial involvement (PI), LVSI, depth of stromal invasion, and tumor size were related to the prognosis of patients with stage IB-IIA CC (P < 0.05). Results of multivariate analysis showed that cell differentiation, clinical stage, and LNM were independent prognostic factors for patients with stage IB-IIA CC. There was no difference in 5-year survival rate between SCC patients and AC patients (87.3% vs. 82.4%; P > 0.05). In AC patients, there was no difference in the 5-year survival rate between patients with ovarian retention and patients with bilateral ovariectomy (75% vs. 86.6%; P > 0.05). CONCLUSIONS: In stage IB-IIA CC, there is no difference in prognosis between AC and SCC. The ovaries of stage IB-IIA1 AC patients under age 45 might be preserved.

[Clinical features and prognosis of cervical adenocarcinoma and adenosquamous carcinoma: an analysis of 237 cases].

OBJECTIVE: To analyze the clinical features and prognosis of cervical adenocarcinoma (AC) and adenosquamous carcinoma of cervix (ASC). METHODS: The clinical data of 237 patients, including 201 cases of AC and 36 cases of ASC (FIGO stage ⅠB1-ⅡA), who underwent surgery in Qilu Hospital between September 2007 and September 2016 were reviewed. Clinical features of two groups were compared, and Kaplan-Meier survival analysis was performed to evaluate the prognosis. RESULTS: A larger proportion of ASC patients had lymphovascular space invasion compared with AC patients (P<0.01), but no significant differences were observed in the age, FIGO stage, size of tumor, depth of stromal invasion, parametrial invasion, lymphatic metastasis and risk grade between two groups (all P>0.05). The 5-year overall survival rates of AC and ASC groups were 79.4% and 78.3%, and the 5-year recurrence-free survival rates were 77.4% and 73.0%. Among patients received concurrent chemoradiotherapy, the 5-year overall survival rates were 71.0% and 61.4%, and the 5-year recurrence-free survival rates were 68.8% abd 61.1%, respectively. No significant differences were observed in 5-year overall survival rates and recurrence-free survival rates between AC and ASC patients (all P>0.05). CONCLUSIONS: Lymphovascular space invasion was more likely to occur in patients with ASC, but there was no significant difference in the prognosis between AC and ASC patients.

Is it necessary to perform routine appendectomy for mucinous ovarian neoplasms? A retrospective study and meta-analysis.

OBJECTIVES: To evaluate whether routine appendectomy is necessary in all patients with mucinous borderline ovarian tumor (mBOT) or mucinous ovarian cancer (MOC) who undergo gynecologic surgery. METHODS: The database of Qilu Hospital was searched for women who underwent appendectomy in a primary surgery for an ovarian tumor between June 2005 and June 2015 and whose final diagnosis was mBOT, MOC or primary appendiceal tumor. A retrospective review was performed, as well as a meta-analysis of the literature to further validate the findings. RESULTS: Seventy-one patients, 29 with mBOT and 42 with malignant mucinous tumors (including 40 with primary MOC and 2 with appendiceal mucinous adenocarcinoma), underwent appendectomy at the time of primary surgery. Among those with mBOT, two (6.9%) appendices were grossly abnormal and pathologically diagnosed with appendiceal implantation by mBOT. In the 42 patients with malignant disease, five (12%) appendices had a grossly abnormal appearance, one (2.4%) was diagnosed with an appendiceal metastasis from MOC and two (4.7%) were primary appendiceal adenocarcinoma. For grossly normal appendices, only one (2.4%) was confirmed to have microscopic metastasis from MOC. The meta-analysis included a total of 914 mBOT and MOC cases with appendectomies, including our current cases. The estimated rate of overall appendiceal pathology is 4.97%, and the pooled odds ratio (OR) showed statistical differences between MOC and mBOT (MOC vs. mBOT, OR=2.15, P<0.05). The estimated malignant pathology rate in macroscopically normal vs. abnormal appendices is 1.4% and 59%, respectively, with an estimated OR up to 97.5 (95% CI 28.1-338.5, P<0.05). CONCLUSION: There is not sufficient evidence to support a routine appendectomy for patients with a grossly normal appendix in mBOT and MOC. A careful intra-operative exploration of the appendix is crucial, but appendectomy is only warranted when the appendix is abnormal.

Characterization of hsa_circ_0004277 as a New Biomarker for Acute Myeloid Leukemia via Circular RNA Profile and Bioinformatics Analysis.

Circular RNAs (circRNAs) represent a widespread class of non-coding RNAs, which drew little attention in the past. Recently, limited data showed their promising future to act as biomarkers in human cancer, but the characteristics and functions remain largely unknown in hematopoietic malignancies, especially in leukemia. In this study, with the help of circRNA microarray, we demonstrated the expression profile of circRNAs in acute myeloid leukemia (AML) patients, and identified a large number of circRNAs possibly expressed in a leukemia specific manner. We also described a circRNA signature related to AML risk-status based on the bioinformatics prediction. In particular, a downregulated circRNA, hsa_circ_0004277, was characterized and functionally evaluated in a cohort of 115 human samples, thus offering a potential diagnostic marker and treatment target in AML. Interestingly, we found chemotherapy could significantly restore the expression of hsa_circ_0004277, indicating the increasing level of hsa_circ_0004277 was associated with successful treatment. Furthermore, a detailed circRNA-miRNA-mRNA interaction network was presented for hsa_circ_0004277, allowing us to better understand its underlying mechanisms for function in AML.

Significance of the Factors Associated With Parametrial Involvement in Stage IB to IIA Cervical Cancer.

OBJECTIVE: The aim was to explore the factors associated with parametrial involvement (PI) in patients with stage IB to IIA cervical cancer. MATERIALS AND METHODS: Medical records of 507 patients were reviewed. Nine factors were analyzed by univariate analysis using χ test and multivariate analysis using logistic regression analysis to screen for factors associated with PI. RESULTS: There were 46 patients with PI. Result of univariate analysis suggested depth of stromal invasion, lymphovascular space invasion (LVSI), and lymph node metastasis, and uterine involvement was associated with PI (P < 0.05 for all). The multivariate analysis model included factors that could be diagnosed by a cone biopsy, and the result suggested nonsquamous histological type and LVSI was the independent factor of PI. The incidence of PI in the patients with no LVSI and squamous cancer was 6.97%. When the patients with inner 1/3 stromal invasion were stratified into those with squamous cancer and no LVSI, the incidence of PI was 1.17%. The incidence of PI in the patients with LVSI and nonsquamous cancer was 33.33%. CONCLUSIONS: The patients with inner 1/3 stromal invasion, no LVSI, and squamous histological type may be considered for less radical surgery. The patients with nonsquamous histological type and LVSI may be considered for radical hysterectomy including a complete resection of parametrium.

The existence of Th22, pure Th17 and Th1 cells in CIN and Cervical Cancer along with their frequency variation in different stages of cervical cancer.

BACKGROUND: Recently, it is found that T-helper (Th) 22 cells are involved in different types of autoimmune and tumor diseases. But, till now, no study has been carried out to understand the involvement of these cells in cervical cancer (CC). METHODS: Flow cytometry was used to determine the expression of interferon gamma (IFN-γ), Interleukin-22 (IL-22), IL-17 in the peripheral blood of healthy controls (HC), CIN and cervical cancer patients. From peripheral blood mononuclear cells (PBMCs), mRNA expression levels of Aryl hydrocarbon receptor (AHR), RAR-related orphan receptor C (RORC), TNF-α and IL-6 were respectively determined. Using the method of ELISA, plasma concentrations of IL-22, IL-17 and TNF-α were examined. RESULTS: Th22 and Th17 cells were elevated in CC and CIN patients. Th1 cells and the plasma concentrations of IL-22 in CC patients were significantly increased compared with HC. In CC patients, an increased prevalence of Th22 cells was associated with lymph node metastases. There was a positive correlation between Th22 and Th17 cells, but an approximately negative correlation between Th22 and Th1 cells in CC patients. The mRNA expression of RORC, TNF-α and IL-6 was significantly high in CC patients. CONCLUSIONS: Our results indicate that there is a higher circulatory frequency of Th22, Th17 and Th1 cells in CC which may conjointly participate in the pathogenesis and growth of CC.

Changes of Th17/Tc17 and Th17/Treg cells in endometrial carcinoma.

OBJECTIVES: T helper 17 (Th17), T cytotoxic 17 (Tc17) and regulatory T (Treg) cells are important factors in the pathogenesis of inflammatory and autoimmune diseases. However, information concerning the roles of these cells in antitumor immunity or endometrial tumorigenesis remains limited. In this study, we aimed to describe the distribution of Th17, Tc17 and Treg cells in endometrial carcinoma patients, and elucidate the probable role of these effector T cells. METHODS: We assessed the expression of interleukin (IL)-17 and Foxp3 in the peripheral blood of endometrial carcinoma patients and healthy controls by flow cytometry to determine the relative numbers of Th17, Tc17 and Treg cells. Th17 cells and Tc17 cells were counted as percentages of the total number of CD3(+) T cells; Treg cells were counted as a percentage of the total number of CD4(+) T cells. We also evaluated Th17 and Tc17 cells in tumor tissue by immunohistochemical staining. IL-17 and IL-10, dominant products of these three cell types, were detected by using enzyme-linked immunosorbent assays. RESULTS: The frequencies of Th17, Tc17 and Treg cells, as well as the serum level of IL-10, were significantly elevated in endometrial carcinoma patients compared to healthy controls. The Th17/Tc17 and Th17/Treg ratios were also observed to change significantly. However, there was no significant difference on the IL-17 levels in the serum. Additionally, immunohistochemistry performed on tumor tissues indicated that the amounts of Th17 and Tc17 increased in the cancer patients. CONCLUSIONS: Our data suggests a probable involvement of Th17, Tc17 and Treg cells in the pathogenesis of endometrial carcinoma. Restoring the balance of these cells may help with the research and development of immunotherapies for endometrial carcinoma.

The top 100 most cited articles on fertility-sparing treatments for cervical cancer: A bibliometric analysis.

Background: The primary objective of this paper was to assess and analyze the top 100 most cited articles currently cited in studies of fertility-sparing treatments for cervical cancer. Methods: Searching the Web of Science Core Collection database for the top 100 most cited articles on fertility-sparing treatments for cervical cancer, different aspects of the articles were analyzed, including countries, journals, institutions, authors, keywords and topics. Results: The search was conducted up to August 2023, and the number of citations for the top 100 articles ranged from 19 to 212. These articles originated from 28 different countries, with Professor Plante, M. from Canada and Professor Sonoda, Y. from the USA having the highest number of articles, both with 10. Professor Plante, M. was the first author of 9 articles and corresponding author of 9 articles. The Memorial Sloan Kettering Cancer Center in the USA published the most articles (21) and received a total of 258 citations. Gynecologic Oncology published 37 of the top 100 articles, with 524 citations and an average of 14.16 citations per article. Conclusions: The study concludes that the USA has made the most significant contributions to this field based on the number of articles, authors, and institutions. Additionally, keyword clustering and burst analysis revealed the research hotspots and future trends in this area.