Hanzi Xu

Predictive role of ARID1A and B2M mutations and the antigen presentation pathway in the efficacy of definitive chemoradiotherapy for cervical cancer

Abstract Background and purpose Definitive chemoradiotherapy (dCRT) is the standard treatment for locally advanced cervical cancer (LACC), yet patients experience considerable variability in disease-free survival (DFS). This study aimed to identify molecular biomarkers associated with response to dCRT in cervical cancer. Materials and methods: We retrospectively analyzed targeted next-generation sequencing data from tumor biopsy samples of 31 patients diagnosed with FIGO stage IIB–IVA LACC. Genetic alterations in cancer-related genes and pathways were assessed to determine associations with DFS. Immune cell infiltration and gene expression were analyzed using data from The Cancer Genome Atlas. Results Genetic alterations were frequently detected in PIK3CA (45.2%), EP300 (25.8%), RB1 (19.4%), FBXW7 (19.4%), and FAT1 (16.1%). Multivariate analysis identified mutations in ARID1A and B2M as independent predictors of poor DFS. Alterations in the antigen processing and presentation pathway were also associated with reduced survival rates. Patients with ARID1A and B2M mutations exhibited decreased immune cell infiltration and impaired antigen presentation, indicating a compromised immune response. Conclusion ARID1A and B2M mutations may serve as potential biomarkers for predicting treatment outcomes in cervical cancer patients undergoing dCRT. Testing for these mutations could help identify patients at higher risk of poor outcomes, guiding personalized treatment strategies to improve survival rates.

Plasma circRNA microarray profiling identifies novel circRNA biomarkers for the diagnosis of ovarian cancer

Abstract Background Circular RNA (circRNA), a class of RNA with a covalent closed circular structure that widely existed in serum and plasma, has been considered an ideal liquid biopsy marker in many diseases. In this study, we employed microarray and qRT-PCR to evaluate the potential circulating circRNAs with diagnostic efficacy in ovarian cancer. Methods We used microarray to explore the circRNA expression profile in ovarian cancer patients’ plasma and quantitative real-time (qRT)-PCR approach to assessing the candidate circRNA’s expression. Then the receiver operating characteristic (ROC) curve was employed to analyze the diagnostic values of candidate circRNAs. The diagnostic model circCOMBO was a combination of hsa_circ_0003972 and hsa_circ_0007288 built by binary logistic regression. Then bioinformatic tools were used to predict their potential mechanisms. Results Hsa_circ_0003972 and hsa_circ_0007288 were downregulated in ovarian cancer patients’ plasma, tissues, and cell lines, comparing with the controls. Hsa_circ_0003972 and hsa_circ_0007288 exhibited diagnostic values with the Area Under Curve (AUC) of 0.724 and 0.790, respectively. circCOMBO showed a better diagnostic utility (AUC: 0.781), while the combination of circCOMBO and carbohydrate antigen 125 (CA125) showed the highest diagnostic value (AUC: 0.923). Furthermore, the higher expression level of hsa_circ_0007288 in both plasma and ovarian cancer tissues was associated with lower lymph node metastasis potential in ovarian cancer. Conclusions Our results revealed that hsa_circ_0003972 and hsa_circ_0007288 may serve as novel circulating biomarkers for ovarian cancer diagnosis.

3D-US and CBCT Dual-guided Radiotherapy for Postoperative Uterine Malignancy: A Primary Workflow Set-up

Introduction: The consistency of clinical target volume is essential to guiding radiotherapy with precision for postoperative uterine malignancy patients. By introducing a three-dimensional ultrasound system (3D-US) into image-guided radiation therapy (IGRT), this study was designed to investigate the initial workflow set-up, the therapeutic potential, and the adverse events of 3D-US and cone-beam computed tomography (CBCT) dual-guided radiotherapy in postoperative uterine malignancy treatment. Methods: From April 2021 to December 2021, postoperative uterine malignancy patients were instructed to follow the previously standard protocol of daily radiation treatment, particularly a 3D-US (Clarity system) guiding was involved before CBCT. Soft-tissue-based displacements resulting from the additional US-IGRT were acquired in the LT (left)/RT (right), ANT (anterior)/POST (posterior), and SUP (superior)/INF(inferior) directions of the patient before fractional treatment. Displacement distributions before and after treatment either from 3D-US or from CBCT were also estimated and compared subsequently, and the urinary and rectal toxicity was further evaluated. Results: All the patients completed radiation treatment as planned. The assessment of 170 scans resulted in a mean displacement of (0.17 ± 0.24) cm, (0.19 ± 0.23) cm, (0.22 ± 0.26) cm for bladder in LT/RT, ANT/POST, and SUP/INF directions. A mean deviation of (0.26 ± 0.22) cm, (0.58 ± 0.5) cm, and (0.3 ± 0.23) cm was also observed for the bladder centroid between the CBCT and computed tomography -simulation images in three directions. Paired comparison between these two guidance shows that the variations from 3D-US are much smaller than those from CBCT in three directions, especially in ANT/POST and SUP/INF directions with significance ( P = 0.000, 0.001, respectively). During treatment, and 0, 3, 6, 9, and 12 months after treatment, there was no severe urinary and rectal toxicity happened. Conclusion: A primary workflow of 3D-US and CBCT dual-guided radiotherapy has been established, which showed great therapeutic potential with mild to moderate urinary and rectal toxicity for postoperative uterine malignancy patients. But the clinical outcomes of this non-invasive technique need to be investigated further.