Alarmin S100A8 imparts chemoresistance of esophageal cancer by reprogramming cancer-associated fibroblasts.

Chemotherapy remains the first-line treatment for advanced esophageal cancer. However, durable benefits are achieved by only a limited subset of individuals due to the elusive chemoresistance. Here, we utilize patient-derived xenografts (PDXs) from esophageal squamous-cell carcinoma to investigate chemoresistance mechanisms in preclinical settings. We observe that activated cancer-associated fibroblasts (CAFs) are enriched in the tumor microenvironment of PDXs resistant to chemotherapy. Mechanistically, we reveal that cancer-cell-derived S100A8 triggers the intracellular RhoA-ROCK-MLC2-MRTF-A pathway by binding to the CD147 receptor of CAFs, inducing CAF polarization and leading to chemoresistance. Therapeutically, we demonstrate that blocking the S100A8-CD147 pathway can improve chemotherapy efficiency. Prognostically, we found the S100A8 levels in peripheral blood can serve as an indicator of chemotherapy responsiveness. Collectively, our study offers a comprehensive understanding of the molecular mechanisms underlying chemoresistance in esophageal cancer and highlights the potential value of S100A8 in the clinical management of esophageal cancer.

Prediction of Postoperative Pathologic Risk Factors in Cervical Cancer Patients Treated with Radical Hysterectomy by Machine Learning.

Pretherapeutic serological parameters play a predictive role in pathologic risk factors (PRF), which correlate with treatment and prognosis in cervical cancer (CC). However, the method of pre-operative prediction to PRF is limited and the clinical availability of machine learning methods remains unknown in CC. Overall, 1260 early-stage CC patients treated with radical hysterectomy (RH) were randomly split into training and test cohorts. Six machine learning classifiers, including Gradient Boosting Machine, Support Vector Machine with Gaussian kernel, Random Forest, Conditional Random Forest, Naive Bayes, and Elastic Net, were used to derive diagnostic information from nine clinical factors and 75 parameters readily available from pretreatment peripheral blood tests. The best results were obtained by RF in deep stromal infiltration prediction with an accuracy of 70.8% and AUC of 0.767. The highest accuracy and AUC for predicting lymphatic metastasis with Cforest were 64.3% and 0.620, respectively. The highest accuracy of prediction for lymphavascular space invasion with EN was 59.7% and the AUC was 0.628. Blood markers, including D-dimer and uric acid, were associated with PRF. Machine learning methods can provide critical diagnostic prediction on PRF in CC before surgical intervention. The use of predictive algorithms may facilitate individualized treatment options through diagnostic stratification.

Mental distress, quality of life and physical symptoms in Chinese women with ovarian cancer receiving olaparib treatment during the COVID-19 pandemic.

Objectives: Women with ovarian cancer (OC) have experienced unprecedented challenges since the novel coronavirus disease-2019 (COVID-19) outbreak in China. We aim to evaluate the experience of psychological status, physical symptoms and quality of life (QoL) and investigate the impact of COVID-19 pandemic on OC patients receiving olaparib. Methods: The survey was conducted online from April 22 to May 12 in 2020. Demographic and clinical questions were listed to collect general information. The degree of insomnia, depression, anxiety, stress symptoms and QoL were assessed by the Chinese versions of the Insomnia Severity Index, the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, the Impact of Event Scale-Revised, and the General Functional Assessment of Cancer Therapy, respectively. Multivariate logistic regression analysis was conducted to analyze the risk factors for mental distress and QoL. Results: A total of 56 respondents coming from 15 various provinces in China participated in the survey. The prevalence of insomnia, depressive, anxiety, stress symptoms and reduced QoL were 37.5, 51.8, 37.5, 30.4, and 51.8%, respectively. Unfavorable disease status, shorter period of olaparib administration, adverse events of olaparib and delay in cancer care were correlated with mental health problems. Reduced QoL was also significantly associated with psychological distress. Conclusions: This study emphasized that mental health problems and reduced QoL should gain more attention in women with OC who are receiving oral olaparib at home. Appropriate psychological healthcare strategies are necessary for OC patients during the COVID-19 pandemic.

Construction of the cervical cancer common terminology for promoting semantic interoperability and utilization of Chinese clinical data.

BACKGROUND: We aimed to build a common terminology in the domain of cervical cancer, named Cervical Cancer Common Terminology (CCCT), that will facilitate clinical data exchange, ensure quality of data and support large scale data analysis. METHODS: The standard concepts and relations of CCCT were collected from ICD-10-CM Chinese Version, ICD-9-PC Chinese Version, officially issued commonly used Chinese clinical terms, Chinese guidelines for diagnosis and treatment of cervical cancer and Chinese medical book Lin Qiaozhi Gynecologic Oncology. 2062 cervical cancer electronic medical records (EMRs) from 16 hospitals, belong to different regions and hospital tiers, were collected for terminology enrichment and building common terms and relations. Concepts hierarchies, terms and relationships were built using Protégé. The performance of natural language processing results was evaluated by average precision, recall, and F1-score. The usability of CCCT were evaluated by terminology coverage. RESULTS: A total of 880 standard concepts, 1182 common terms, 16 relations and 6 attributes were defined in CCCT, which organized in 6 levels and 11 classes. Initial evaluation of the natural language processing results demonstrated average precision, recall, and F1-score percentages of 96%, 72.6%, and 88.5%. The average terminology coverage for three classes of terms, clinical manifestation, treatment, and pathology, were 87.22%, 92.63%, and 89.85%, respectively. Flexible Chinese expressions exist between regions, traditions, cultures, and language habits within the country, linguistic variations in different settings and diverse translation of introduced western language terms are the main reasons of uncovered terms. CONCLUSIONS: Our study demonstrated the initial results of CCCT construction. This study is an ongoing work, with the update of medical knowledge, more standard clinical concepts will be added in, and with more EMRs to be collected and analyzed, the term coverage will be continuing improved. In the future, CCCT will effectively support clinical data analysis in large scale.

A Preoperative Nomogram for Predicting Chemoresistance to Neoadjuvant Chemotherapy in Patients with Locally Advanced Cervical Squamous Carcinoma Treated with Radical Hysterectomy.

PURPOSE: This study aimed to investigate the factors associated with chemoresistance to neoadjuvant chemotherapy (NACT) followed by radical hysterectomy (RH) and construct a nomogram to predict the chemoresistance in patients with locally advanced cervical squamous carcinoma (LACSC). MATERIALS AND METHODS: This retrospective study included 516 patients with International Federation of Gynecology and Obstetrics (2003) stage IB2 and IIA2 cervical cancer treated with NACT and RH between 2007 and 2017. Clinicopathologic data were collected, and patients were assigned to training (n=381) and validation (n=135) sets. Univariate and multivariate analyses were performed to analyze factors associated with chemoresistance to NACT. A nomogram was built using the multivariate logistic regression analysis results. We evaluated the discriminative ability and accuracy of the model using a concordance index and a calibration curve. The predictive probability of chemoresistance to NACT was defined as > 34%. RESULTS: Multivariate analysis confirmed menopausal status, clinical tumor diameter, serum squamous cell carcinoma antigen level, and parametrial invasion on magnetic resonance imaging before treatment as independent prognostic factors associated with chemoresistance to NACT. The concordance indices of the nomogram for training and validation sets were 0.861 (95% confidence interval [CI], 0.822 to 0.900) and 0.807 (95% CI, 0.807 to 0.888), respectively. Calibration plots revealed a good fit between the modelpredicted probabilities and actual probabilities (Hosmer-Lemeshow test, p=0.597). Furthermore, grouping based on the nomogram was associated with progression-free survival. CONCLUSION: We developed a nomogram for predicting chemoresistance in LACSC patients treated with RH. This nomogram can help physicians make clinical decisions regarding primary management and postoperative follow-up of the patients.

Characteristics and treatment results of recurrence in adult-type granulosa cell tumor of ovary.

BACKGROUND: The aim of this study was to explore the clinicopathological characteristics of recurrent adult-type granulosa cell tumor of the ovary (AGCOT) and evaluated the treatment results to define the prognostic parameters for survival after recurrence. RESULTS: A retrospective review of 40 patients with recurrent AGCOT, who were treated in the Cancer Hospital at the Chinese Academy of Medical Sciences from 2000 to 2015 was conducted. The impact of clinical and pathological characteristics, progression-free survival (PFS), and post-recurrence therapeutic approaches on prognosis were analyzed. Among the 40 recurrent patients, there were 10 cases where the relapse was uncontrolled, 24 cases had second relapses, and 6 cases without further relapses at the time of our follow-up. The median PFS was 61 months (range, 7-408 months), and the median time interval between the first and the second relapses (R-PFS) was 25 months (range, 0-94 months). The median time interval between the first relapse and death (R-OS) was 90 months (range, 2-216 months). PFS ≥ 61 months (P = 0.004) and post-recurrence therapeutic approach (P < 0.001) were independent risk factors for repeated recurrences. The age at recurrence (P = 0.031) and post-recurrence therapeutic approach (P = 0.001) were independent risk factors for death after recurrence. CONCLUSION: Among patients with recurrent AGCOT, those with long PFS had good prognoses. Maximal cytoreductive effort should be made after recurrence. Complete resection and postoperative adjuvant chemotherapy may improve the prognosis of patients with recurrent AGCOT.

Separate lateral parametrial lymph node dissection improves detection rate of parametrial lymph node metastasis in early-stage cervical cancer: 10-year clinical evaluation in a single center in China.

OBJECTIVE: To investigate the clinical significance of separate lateral parametrial lymph node dissection (LPLND) in improving parametrial lymph node (PLN) and its metastasis detection rate during radical hysterectomy for early-stage cervical cancer. METHODS: From July 2007 to August 2017, 2,695 patients with cervical cancer in stage IB1-IIA2 underwent radical hysterectomy were included. Of these patients, 368 underwent separate dissection of PLNs using the LPLND method, and 2,327 patients underwent conventional radical hysterectomy (CRH). We compared the surgical parameters, PLN detection rate and PLN metastasis rate between the two groups. RESULTS: Compared with CRH group, the rate of laparoscopic surgery was higher (60.3% vs. 15.9%, P<0.001), and the blood transfusion rate was lower (19.0%vs. 29.0%, P<0.001) in the LPLND group. PLNs were detected in 356 cases (96.7%) in the LPLND group, and 270 cases (11.6%) in the CRH group (P<0.001), respectively. The number of PLNs detected in the LPLND group was higher than that in the CRH group (median 3vs. 1, P<0.001). The PLN metastases were detected in 25 cases (6.8%) in the LPLND group, and 18 cases (0.8%) in the CRH group (P<0.001), respectively. In multivariable analysis, LPLND is an independent factor not only for PLN detection [odds ratio (OR)=228.999, 95% confidence interval (95% CI): 124.661-420.664; P<0.001], but also for PLN metastasis identification (OR=10.867, 95% CI: 5.381-21.946; P<0.001). CONCLUSIONS: LPLND is feasible and safe. The surgical method significantly improves the detection rate of PLN and avoids omission of PLN metastasis during radical hysterectomy for early-stage cervical cancer.