Ping Liu

Water-Soluble Fluorescent Sensors for Quantification of Trace Cisplatin in Body Fluids from Clinical Cancer Patients

Accurate quantification of cisplatin (cDDP) in body fluids (blood, urine, and ascites) is crucial in monitoring therapeutic processes, assessing drug metabolism, and optimizing treatment schedules for cancer patients. Nonetheless, due to the inherent fluorescence and complexity of the body fluid matrix, along with the low cDDP concentrations in these fluids during treatment, using fluorescent sensors for fluid detection remains a subject of ongoing research. Herein, a series of water-soluble cDDP-activatable fluorescent sensors was rationally constructed by introducing thioether groups to the xanthene skeleton based on the chalcogenophilicity of platinum. These sensors exhibit excellent sensitivity and certain anti-interference capabilities for sensing cDDP in living cells, rat tissues, and zebrafish. Especially, with a simplified sample pretreatment procedure, for the first time,

Comparison of oncological outcomes between radical hysterectomy and radiochemotherapy for International Federation of Gynecology and Obstetrics 2018 stage IIIC1 cervical adenocarcinoma: A retrospective multicenter cohort study

AbstractBackgroundTo compare oncological outcomes of radical hysterectomy (RH) and radiochemotherapy (R‐CT) for stage IIIC1 (FIGO 2018) cervical adenocarcinoma patients.MethodsBased on the Chinese Cervical Cancer Clinical Diagnosis and Treatment Project Database, we retrospectively reviewed 236 cases of FIGO stage IIIC1 cervical adenocarcinoma diagnosed between 2005 and 2019. The 5‐year overall survival (OS) and 5‐year disease‐free survival (DFS) rates were compared between the two treatment groups using multivariate Cox regression models and the log‐rank test, both in the overall study population and after propensity score matching (PSM).ResultsFrom 63 926 patients, we selected 236 cases, including 203 in the RH group and 33 in the R‐CT group. In the overall study population, R‐CT was associated with significantly worse 5‐year OS (51.8% vs. 67.2%, p < 0.05) and 5‐year DFS (43.1% vs. 60.1%, p < 0.05) compared to RH. Multivariate analysis revealed that R‐CT was an independent risk factor for 5‐year DFS (hazard ratio [HR] = 2.226, 95% confidence interval [CI] 1.141–4.343, p < 0.05) but not for 5‐year OS (HR = 1.834, 95% CI: 0.829–4.061, p > 0.05) in FIGO stage IIIC1 cervical adenocarcinoma. After matching (n = 26 in R‐CT group vs. 73 in RH group), the R‐CT group showed significantly lower 5‐year OS (50.3% vs. 77.4%, p < 0.05) and DFS (38.2% vs. 65.0%, p < 0.05) compared to the RH group. In the matched cohort, R‐CT remained an independent risk factor for 5‐year DFS (HR = 2.299, 95% CI: 1.113–4.750, p < 0.05) but not for 5‐year OS (HR = 1.926, 95% CI: 0.792–4.682, p > 0.05).ConclusionAmong patients with stage FIGO 2018 IIIC1 cervical cancer adenocarcinoma, R‐CT was not associated with better oncological outcomes than RH. Radiotherapy should not be the only recommended treatment.

Magnetic resonance imaging for the non-invasive diagnosis in patients with ovarian cancer

Abstract Background: In developed nations, ovarian cancer has resulted in the most fatalities from gynecological cancer. Laparoscopy is primarily utilized as the test to diagnose ovarian cancer. Besides being costly, there are surgical risks associated with laparoscopies. At present, clinical practitioners have access to non-invasive tests for diagnosing ovarian cancer. This study aims to evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) for diagnosing ovarian cancer. Methods: In order to obtain eligible studies, cross-sectional studies or randomized controlled trials are searched in electronic databases. The databases include 5 English databases (PubMed, the Cochrane Library, PsycINFO, EMBASE, and Web of Science) and 3 Chinese databases (China Biomedical Literature Database, China National Knowledge Infrastructure, and WanFang database). The databases are searched from their origin to October 2020. Quality Assessment of Diagnostic Accuracy Studies-2 is used to assess the methodological quality of the selected studies. RevMan 5.3 and SAS NLMIXED software are used to assess the data synthesis, sensitivity analysis, and risk of bias assessment. Results: This study evaluates the pooled diagnostic value of MRI for diagnosing ovarian cancer. Conclusions: This study will summarize previously published evidence of MRI in relation to diagnosing ovarian cancer. Ethics and dissemination: Since this study does not utilize data from patients, this protocol does not require ethical approval. Protocol registration number: DOI 10.17605/OSF.IO/A6SPQ (https://osf.io/a6spq)

Anti‐oncogenic PTEN induces ovarian cancer cell senescence by targeting P21

AbstractDeletion and mutation of phosphatase and tensin homolog deleted on chromosome10 (PTEN) are closely associated with the occurrence of tumors. Tumor suppressor gene PTEN mutation plays an important role in the pathogenesis of ovarian cancer. However, it has been unclear whether it can regulate the senescence of ovarian cancer cells. We speculated that PTEN might inhibit the occurrence and development of ovarian cancer by promoting the expression of P21. We found that the expression of TRIM39 in human ovarian cancer was significantly diminished. In SKOV3 cells treated with naringin, the expression of TRIM39, which binds P21 and inhibits P21 degradation, was significantly elevated. Real‐time polymerase chain reaction (PCR), Western blot, and immunofluorescence were used to detected the expression of PTEN, p21, and TRIM39, β‐galactosidase Staining was used to detect cell senescence, Ki67 staining was used to observe cell proliferation, Trim39 interference or overexpression assay was used to detect its function. We speculated that PTEN might promote SKOV3 cell senescence by increasing TRIM39 expression and decreasing P21 degradation. Furthermore, by interfering with TRIM39 in SKOV3 cells, we found that the expression of P21 was downregulated, and the number of senescent SKOV3 cells decreased. With overexpression of TRIM39 in SKOV3 cells, the expression of P21 was upregulated, and the number of senescent SKOV3 cells increased. When naringin, a PTEN agonist, was added to SKOV3 cells in which TRIM39 protein was interfered with, the expression of P21 was significantly lower than that in the control group, and the number of senescent ovarian cancer cells was significantly diminished. Our results indicated that PTEN maintained the stability of P21 and decreased the degradation of P21 by increasing TRIM39 expression, thus promoting the senescence of SKOV3 cells, and PTEN maintained the stability of p21 and promoted the aging of SKOV3 cells might be a novel therapeutic target for ovarian cancer.

Comparison between laparoscopic and abdominal radical hysterectomy for stage IB1 and tumor size <2 cm cervical cancer with visible or invisible tumors: a multicentre retrospective study

To compare 5-year disease-free survival (DFS) and overall survival (OS) rates of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for stage IB1 and tumor size <2 cm with visible or invisible tumors. We retrospectively compared the oncological outcomes of 1,484 cervical cancer patients with IB1 and tumor size <2 cm on final pathology, who received ARH (n=899) or LRH (n=585) between January 2004 and December 2016. Patients were divided into visible tumor subgroup (ARH: n=668, LRH: n=444) and invisible tumor subgroup (ARH: n=231, LRH: n=141) according to tumor type. LRH and ARH showed similar 5-year DFS and OS rates (93.3% vs. 93.1%, p=0.997; 96.2% vs. 97.5%, p=0.351) in total study population. LRH was not associated with worse 5-year DFS rate (hazard ratio [HR]=0.96; 95% confidence interval [CI]=0.58-1.58; p=0.871) or OS rate (HR=1.37; 95% CI=0.65-2.89; p=0.409) by multivariable analysis. In the visible tumor subgroups, LRH and ARH showed similar 5-year DFS and OS rates (91.9% vs. 91.9%, p=0.933; 95.0% vs. 96.9%, p=0.276), and LRH was not associated with worse 5-year DFS or OS rate (p=0.804, p=0.324). In the invisible tumor subgroups, LRH and ARH also showed similar 5-year DFS and OS rates (97.3% vs. 97.1%, p=0.815; 100% vs. 99.5%, p=0.449), and LRH was not associated with worse 5-year DFS rate (p=0.723). Among patients with stage IB1 and tumor size <2 cm, whether the tumor is visible or not, the oncological outcomes of LRH and ARH among cervical cancer patients are comparable. This suggests that LRH may be suitable for stage IB1 and tumor size <2 cm with visible or invisible tumors. International Clinical Trials Registry Platform Identifier: CHiCTR180017778.

Comparison between robot-assisted radical hysterectomy and abdominal radical hysterectomy for cervical cancer: A multicentre retrospective study

To compare 3-year overall survival (OS) and disease-free survival (DFS) rates of robot-assisted radical hysterectomy (RRH) and abdominal radical hysterectomy (ARH) for cervical cancer. We retrospectively compared the oncological outcomes of 10,314 cervical cancer patients who received RRH (n = 1048) or ARH (n = 9266) and whose stages were IA1 with lymphovascular space invasion (LVSI)-IIA2. Kaplan-Meier survival analysis and log-rank tests were used to compare the 3-year OS and DFS rates between the RRH and ARH groups. Cox proportional hazards model and propensity score matching was used to estimate the surgical approach-specific survival. RRH and ARH showed similar 3-year OS and DFS rates (93.5% vs. 94.1%, p = 0.486; 90.0% vs. 90.4%, p = 0.302). RRH was not associated with a lower 3-year OS rate by the multivariable analysis (HR 1.23, 95% CI 0.89-1.70, p = 0.206), but it was associated with a lower 3-year DFS rate (HR 1.20, 95% CI 1.09-1.52, p = 0.035). After propensity score matching, patients who underwent RRH had decreased 3-year OS and DFS rates compared to those who underwent ARH (94.4% vs. 97.8%, p = 0.002; 91.1% vs. 95.4%, p = 0.001), and RRH was associated with lower 3-year OS and DFS rates. Among patients with stage IB1 and tumor size <2 cm, RRH was not associated with decreased 3-year OS and DFS rates (HR1.688, 95% CI 0.423-6.734, p = 0.458; HR1.267, 95%CI 0.518-3.098, p = 0.604). Overall, RRH was associated with worse 3-year oncological outcomes than ARH in patients with FIGO stage IA1 with LVSI- IIA2 cervical cancer. However, RRH showed similar 3-year oncological outcomes with ARH among those with stage IB1 and tumor size <2 cm.

Risk factors for and delayed recognition of genitourinary fistula following radical hysterectomy for cervical cancer: a population-based analysis

This study aimed to identify the risk factors for genitourinary fistulas and delayed fistula recognition after radical hysterectomy for cervical cancer. This study was a retrospective analysis of data collected in the Major Surgical complications of Cervical Cancer in China (MSCCCC) database from 2004-2016. Data on sociodemographic characteristics, clinical characteristics, and hospital characteristics were extracted. Differences in the odds of genitourinary fistula development were investigated with multivariate logistic regression analyses, and differences in the time to recognition of genitourinary fistula were assessed by Kruskal-Wallis test. In this study, 23,404 patients met the inclusion criteria. Surgery in a cancer center, a women's and children's hospital, a facility in a first-tier city, or southwest region, stage IIA, type C1 hysterectomy, laparoscopic surgery and ureteral injury were associated with a higher risk of ureterovaginal fistula (UVF) (p<0.050). Surgery in southwest region, bladder injury and laparoscopic surgery were associated with greater odds of vesicovaginal fistula (VVF) (p<0.050). Surgery at cancer centers and high-volume hospitals was associated with an increase in the median time to UVF recognition (p=0.016; p=0.005). International Federation of Gynecology and Obstetrics (FIGO) stage IIA1-IIB was associated with delayed recognition of VVF (p=0.040). Intraoperative urinary tract injury and surgical approach were associated with differences in the development of UVFs and VVFs. Patients who underwent surgery in cancer centers and high-volume hospitals were more likely to experience delayed recognition of UVF. Patients with FIGO stage IIA1-IIB disease were more likely to experience delayed recognition of VVF.

Development of a deep learning‐based nomogram for predicting lymph node metastasis in cervical cancer: A multicenter study

Laparoscopic versus open radical hysterectomy in FIGO 2018 early‐stage cervical adenocarcinoma: Long‐term survival outcomes after propensity score matching

AbstractObjectiveTo compare the long‐term survival outcomes of laparoscopic radical hysterectomy (LRH) and open radical hysterectomy (ORH) in International Federation of Gynecology and Obstetrics (FIGO) 2018 early‐stage cervical adenocarcinoma.MethodsBased on the clinical diagnosis and treatment for cervical cancer in mainland China (Four C) database, the medical records of 1098 patients with FIGO 2018 early‐stage cervical adenocarcinoma were retrospectively reviewed. Long‐term and short‐term survival outcomes of the two groups were compared using a multivariate Cox regression model and the log‐rank method in the whole study population and after propensity score matching.ResultsThere was no difference in disease‐free survival (hazard ratio [HR] 0.921, 95% confidence interval [CI]: 0.532–1.595, p = 0.770) and overall survival (HR 1.168, 95% CI: 0.526–2.592, p = 0.702) between LRH (n = 468) and ORH (n = 468) in the risk‐adjusted analysis. LRH resulted in significantly lower estimated blood loss (342.7 vs. 157.5 mL, p &lt; 0.001) and shorter postoperative anal exhaust time (2.8 vs. 2.5 days, p &lt; 0.001) in risk‐adjusted analysis. The overall rates of intraoperative complications (2.4% vs. 4.3%, p = 0.100) and postoperative complications (7.5% vs. 6.2%, p = 0.437) showed no significant difference between the two groups. However, the LRH group had a significantly higher incidence of ureter injury (0.4% vs. 2.4%, p = 0.012) and great vessel injury (0.0% vs. 0.9%, p = 0.045) compared to the other group. No statistical variation in the site of recurrence was observed between the two groups (p = 0.613).ConclusionsLRH has comparable survival outcomes with ORH and was associated with earlier recovery in FIGO 2018 early‐stage adenocarcinoma of the uterine cervix. However, the LRH group had higher risk of ureter injury and great vessel injury.

Identification of ferroptosis-related molecular subtypes and a methylation-related ferroptosis gene prognostic signature in cervical squamous cell carcinoma

We aimed to investigate the molecular characteristics of cervical squamous cell carcinoma (CESC) by analyzing ferroptosis-related gene (FRG) expression data to predict prognosis. Gene expression and clinicopathological data of patients with CESC were collected from the Cancer Genome Atlas and the Genotype-Tissue Expression databases. Using Cox regression analysis, we identified 21 FRGs associated with prognosis. Cluster analysis categorized patients into subgroups based on these genes and compared their clinicopathological, biological, and immune infiltration features. FRG methylation levels were examined, and a risk model based on such FRG methylation levels was constructed using LASSO and Cox regression analyses. The model's predictive capacity was validated, and the relationships between the risk score and immune infiltration, tumor microenvironment, and drug sensitivity were explored. FRG methylation in CESC tissues was validated by immunohistochemistry. We identified 21 FRGs associated with CESC prognosis. Patients were stratified into two subtypes based on these genes, they showed differences in prognosis, immune cell types, and immune checkpoint expression. A three-gene risk score (including AQP3, MGST1, and TFRC) was generated, and the low-risk group showed better overall survival. The high-risk and low-risk groups differed in terms of immune infiltration, gene mutations, and drug sensitivity. Experimental validation confirmed the upregulation of AQP3 and TFRC, whereas MGST1 expression was not significantly altered in CESC tissues compared with that in normal cervical tissues. This study highlights the potential role of FRG methylation in predicting CESC prognosis and provides a personalized assessment of immune responses in patients with CESC.

Rationality of FIGO 2018 IIIC restaging of cervical cancer according to local tumor size: A cohort study

AbstractIntroductionFIGO 2018 IIIC remains controversial for the heterogeneity of its prognoses. To ensure a better management of cervical cancer patients in Stage IIIC, a revision of the FIGO IIIC version classification is required according to local tumor size.Material and methodsWe retrospectively enrolled cervical cancer patients of FIGO 2018 Stages I–IIIC who had undergone radical surgery or chemoradiotherapy. Based on the tumor factors from the Tumor Node Metastasis staging system, IIIC cases were divided into IIIC‐T1, IIIC‐T2a, IIIC‐T2b, and IIIC‐(T3a+T3b). Oncologcial outcomes of all stages were compared.ResultsA total of 63 926 cervical cancer cases were identified, among which 9452 fulfilled the inclusion criteria and were included in this study. Kaplan–Meier pairwise analysis showed that: the oncology outcomes of I and IIA were significantly better than of IIB, IIIA+IIIB, and IIIC; the oncology outcome of IIIC‐(T1‐T2b) was significantly better than of IIIA+IIIB and IIIC‐(T3a+T3b); no significant difference was noted between IIB and IIIC‐(T1‐T2b), or IIIC‐(T3a+T3b) and IIIA+IIIB. Multivariate analysis indicated that, compared with IIIC‐T1, Stages T2a, T2b, IIIA+IIIB and IIIC‐(T3a+T3b) were associated with a higher risk of death and recurrence/death. There was no significant difference in the risk of death or recurrence/death between patients with IIIC‐(T1‐T2b) and IIB. Also, compared with IIB, IIIC‐(T3a+T3b) was associated with a higher risk of death and recurrence/death. No significant differences in the risk of death and recurrence/death were noted between IIIC‐(T3a+T3b) and IIIA+IIIB.ConclusionsIn terms of oncology outcomes of the study, FIGO 2018 Stage IIIC of cervical cancer is unreasonable. Stages IIIC‐T1, T2a, and T2b may be integrated as IIC, and it might be unnecessary for T3a/T3b cases to be subdivided by lymph node status.

Which factors predict parametrial involvement in stage IB cervical cancer? A Chinese multicentre study

To explore the clinicopathological risk factors influencing parametrial involvement (PI) in stage IB cervical cancer patients and compare the oncological outcomes between Q-M type B radical hysterectomy (RH) group and Q-M type C RH group. Univariate and multivariate analyses were performed to explore the clinicopathological factors related to PI. Overall survival (OS) and disease-free survival (DFS) in patients with stage IB cervical cancer who underwent Q-M type B or Q-M type C RH under different circumstances of PI were also compared before and after propensity score matching (1:1 matching). A total of 6358 patients were enrolled in this study. Depth of stromal invasion>1/2 (HR: 3.139, 95% CI: 1.550-6.360; P = 0.001), vaginal margin (+) (HR: 4.271, 95% CI: 1.368-13.156; P = 0.011), lymphovascular space invasion (LVSI) (+) (HR: 2.238, 95% CI: 1.353-3.701; P = 0.002) and lymph node metastases (HR: 5.173, 95% CI: 3.091-8.658; P < 0.001) were associated with PI. Among the 6273 patients with negative PI, those in the Q-M type B RH group had a higher 5-year OS and DFS than those in the Q-M type C RH group before and after 1:1 matching. Among the 85 patients with positive PI, Q-M type C RH showed no survival benefits before and after 1:1 matching. Stage IB cervical cancer patients with no lymph node metastasis, LVSI(-) and depth of stromal invasion ≤1/2 may be considered for Q-M type B radical hysterectomy.

Postoperative management of FIGO 2018 stage IIA1 cervical squamous cell carcinoma with only one intermediate‐risk factor: Is radiotherapy needed?

AbstractObjectiveTo investigate whether postoperative radiotherapy is required for FIGO 2018 stage IIA1 cervical squamous cell carcinoma patients with only one intermediate‐risk factor.MethodsThis was a multicenter retrospective study. The selected patients were classified into no postoperative adjuvant therapy and postoperative radiotherapy groups. The 5‐year overall survival (OS) and disease‐free survival (DFS) rates were compared.ResultsIn total, 159 patients with no postoperative adjuvant therapy and 179 patients with postoperative radiotherapy were included, with the former group showing a lower OS but no difference in DFS. No postoperative adjuvant therapy was an independent risk factor for patient mortality. Patients were also stratified by tumor diameter: 56 patients had a tumor diameter ≤2 cm, comprising 32 patients with postoperative radiotherapy and 24 patients without (no between‐group difference was found); 272 patients had a tumor diameter &gt;2 cm, comprising 122 patients with postoperative radiotherapy and 150 patients without, with the former group showing a higher OS, and no postoperative adjuvant therapy was an independent risk factor for patient mortality.ConclusionFor FIGO 2018 stage IIA1 cervical squamous cell carcinoma patients with only one intermediate‐risk factor and a tumor diameter &gt;2 cm, postoperative radiotherapy is likely beneficial to improve prognosis.