Lijuan Zou

Prognostic values of tumor size and location in early stage endometrial cancer patients who received radiotherapy

To investigate the correlation between tumor size, tumor location, and prognosis in patients with early-stage endometrial cancer (EC) receiving adjuvant radiotherapy. Data of patients who had been treated for stage I-II EC from March 1999 to September 2017 in 13 tertiary hospitals in China was screened. Cox regression analysis was performed to investigate associations between tumor size, tumor location, and other clinical or pathological factors with cancer-specific survival (CSS) and distant metastasis failure-free survival (DMFS). The relationship between tumor size as a continuous variable and prognosis was demonstrated by restricted cubic splines. Prognostic models were constructed as nomograms and evaluated by Harrell's C-index, calibration curves and receiver operating characteristic (ROC) curves. The study cohort comprised 805 patients with a median follow-up of 61 months and a median tumor size of 3.0 cm (range 0.2-15.0 cm). Lower uterine segment involvement (LUSI) was found in 243 patients (30.2%). Tumor size and LUSI were identified to be independent prognostic factors for CSS. Further, tumor size was an independent predictor of DMFS. A broadly positive relationship between poor survival and tumor size as a continuous variable was visualized in terms of hazard ratios. Nomograms constructed and evaluated for CSS and DMFS had satisfactory calibration curves and C-indexes of 0.847 and 0.716, respectively. The area under the ROC curves for 3- and 5-year ROC ranged from 0.718 to 0.890. Tumor size and LUSI are independent prognostic factors in early-stage EC patients who have received radiotherapy. Integrating these variables into prognostic models would improve predictive ability.

Dynamic analysis of circulating tumor DNA to predict prognosis and monitor therapeutic response in metastatic relapsed cervical cancer

AbstractLimited and inefficient treatment options exist for metastatic relapsed cervical cancer (MRCC), and there are currently no reliable indicators to guide therapeutic selection. We performed deep sequencing analyses targeting 322 cancer‐related genes in plasma cell‐free DNA and matched white blood cells in 173 serial blood samples from 82 locally advanced CC (LACC) or MRCC patients and when possible during treatment. We identified five notable nonsynonymous mutant genes (PIK3CA, BRAF, GNA11, FBXW7 and CDH1) in the MRCC samples as the metastatic relapse significantly mutated (MSG) genes and found that MRCC patients with any detectable MSG mutations had significantly shorter progression‐free survival (PFS) (P = .005) and overall survival (OS) (P = .007) times than those without detectable MSG mutations. Additionally, analyses of matched prechemotherapy and postchemotherapy plasma revealed that a reduction in the number of MSG mutations after chemotherapy was significantly associated with partial remission (PR) and stable disease (SD) (P = .007). Among the patients included in the longitudinal tracking ctDNA analysis, an increase in MSG mutations was observed earlier in response to disease progression than radiological imaging. Our results outline the mutation profiles of MRCC. We show how longitudinal monitoring with ctDNA in liquid biopsy samples provides both predictive and prognostic information during treatment.

Sensitization of cervical cancer cells to radiation by the cyclin-dependent kinase inhibitor dinaciclib

Dinaciclib is a selective cyclin-dependent kinase inhibitor, but its radiosensitizing effect remains unclear. The aim of this study is to investigate the radiosensitizing effect of Dinaciclib on cervical cancer cells. Two cervical cancer cell lines, Hela and Siha, were selected, and the IC50 was determined by CCK8. The radiosensitizing effect of Dinaciclib was verified by plate cloning assay, and the G2/M phase arrest and apoptosis of IR cells were verified by flow cytometry. Immunofluorescence assay was used to verify the formation of γH2AX foci following DNA damage. Western blot was performed to detect cell cycle, apoptosis, autophagy, and DNA damage-related pathways. Dinaciclib increased the cell sensitivity to IR. IR induced G2/M phase arrest and apoptosis, and Dinaciclib enhanced this effect. Further, Dinaciclib delayed DNA repair, including non-homologous end joining repair and homologous recombination repair, and reduced the expression of DNA repair proteins Ku80 (SiHa cells), Ku70, and RAD51, as well as the expression of apoptotic marker Bcl-2. The expression of autophagy marker Beclin1 induced tumor cell death and increased the formation of DNA damage marker γH2AX foci. Dinaciclib improves the sensitivity of cervical cancer cells to IR by inducing cell cycle arrest, delaying DNA repair, and increasing apoptosis. However, further research is needed to unravel the complexity of DNA repair pathways.

The Exploration of Personalized ctDNA Based MRD in the Clinical Significance of Cervical Cancer

This study plans to enroll 80 patients with locally advanced cervical cancer (stage IB-ⅣA) confirmed by histology or cytology (according to the 2018 FIGO staging standard), who are expected to receive surgical resection or curative radiotherapy and chemotherapy. Collect baseline tumor tissue samples from patients during the treatment period, as well as peripheral blood samples (20 ml/time) from multiple treatment timepoints. Mutations in tumor tissue were detected by the 1021 genes panel, then personalized MRD monitoring probes were customized for patients, allowing for multi node peripheral blood sample ctDNA detection of enrolled patients. The clinical significance of ctDNA in prognostic stratification, recurrence monitoring, and efficacy prediction in surgical/non-surgical cervical cancer patients was explored. And compare the consistency and differences between ctDNA detection technology, imaging, and blood tumor markers in monitoring tumor disease progression, and evaluate the correlation between ctDNA status after curative treatment and patient PFS and RFS.