A new 4-gene-based prognostic model accurately predicts breast cancer prognosis and immunotherapy response by integrating WGCNA and bioinformatics analysis.

Background: Breast cancer (BRCA) is a common malignancy in women, and its resistance to immunotherapy is a major challenge. Abnormal expression of genes is important in the occurrence and development of BRCA and may also affect the prognosis of patients. Although many BRCA prognosis model scores have been developed, they are only applicable to a limited number of disease subtypes. Our goal is to develop a new prognostic score that is more accurate and applicable to a wider range of BRCA patients. Methods: BRCA patient data from The Cancer Genome Atlas database was used to identify breast cancer-related genes (BRGs). Differential expression analysis of BRGs was performed using the 'limma' package in R. Prognostic BRGs were identified using co-expression and univariate Cox analysis. A predictive model of four BRGs was established using Cox regression and the LASSO algorithm. Model performance was evaluated using K-M survival and receiver operating characteristic curve analysis. The predictive ability of the signature in immune microenvironment and immunotherapy was investigated. In vitro experiments validated POLQ function. Results: Our study identified a four-BRG prognostic signature that outperformed conventional clinicopathological characteristics in predicting survival outcomes in BRCA patients. The signature effectively stratified BRCA patients into high- and low-risk groups and showed potential in predicting the response to immunotherapy. Notably, significant differences were observed in immune cell abundance between the two groups. In vitro experiments demonstrated that POLQ knockdown significantly reduced the viability, proliferation, and invasion capacity of MDA-MB-231 or HCC1806 cells. Conclusion: Our 4-BRG signature has the potential as an independent biomarker for predicting prognosis and treatment response in BRCA patients, complementing existing clinicopathological characteristics.

Theoretical substantiation of biological efficacy enhancement for ß-delayed particle decay (9)C beam: A Monte Carlo study in combination with analysis with the local effect model approach.

PURPOSE: To improve the efficacy of heavy ion therapy, ß-delayed particle decay (9)C beam as a double irradiation source for cancer therapy has been proposed. The authors' previous experiment showed that relative biological effectiveness (RBE) values at the depths around the Bragg peak of a (9)C beam were enhanced and compared to its stable counterpart (12)C beam. The purpose of this study was to explore the nature of the biological efficacy enhancement theoretically. METHODS: A Monte Carlo simulation study was conducted in this study. First a simplified cell model was established so as to form a tumor tissue. Subsequently, the tumor tissue was imported into the Monte Carlo simulation software package gate and then the tumor cells were virtually irradiated with comparable (9)C and (12)C beams, respectively, in the simulations. The transportation and particle deposition data of the (9)C and (12)C beams, derived from the gate simulations, were analyzed with the authors' local effect model implementation so as to deduce cell survival fractions. RESULTS: The particles emitted from the decay process of deposited (9)C particles around a cell nucleus increased the dose delivered to the nucleus and elicited clustered damages around the secondary particles' trajectories. Therefore, compared to the (12)C beam, the RBE value of the (9)C beam increased at the depths around their Bragg peaks. CONCLUSIONS: Collectively, the increased local doses and clustered damages due to the decayed particles emitted from deposited (9)C particles led to the RBE enhancement in contrast with the (12)C beam. Thus, the enhanced RBE effect of a (9)C beam for a simplified tumor model was shown theoretically in this study.

Respiratory motion management using audio-visual biofeedback for respiratory-gated radiotherapy of synchrotron-based pulsed heavy-ion beam delivery.

PURPOSE: To efficiently deliver respiratory-gated radiation during synchrotron-based pulsed heavy-ion radiotherapy, a novel respiratory guidance method combining a personalized audio-visual biofeedback (BFB) system, breath hold (BH), and synchrotron-based gating was designed to help patients synchronize their respiratory patterns with synchrotron pulses and to overcome typical limitations such as low efficiency, residual motion, and discomfort. METHODS: In-house software was developed to acquire body surface marker positions and display BFB, gating signals, and real-time beam profiles on a LED screen. Patients were prompted to perform short BHs or short deep breath holds (SDBH) with the aid of BFB following a personalized standard BH/SDBH (stBH/stSDBH) guiding curve or their own representative BH/SDBH (reBH/reSDBH) guiding curve. A practical simulation was performed for a group of 15 volunteers to evaluate the feasibility and effectiveness of this method. Effective dose rates (EDRs), mean absolute errors between the guiding curves and the measured curves, and mean absolute deviations of the measured curves were obtained within 10%-50% duty cycles (DCs) that were synchronized with the synchrotron's flat-top phase. RESULTS: All maneuvers for an individual volunteer took approximately half an hour, and no one experienced discomfort during the maneuvers. Using the respiratory guidance methods, the magnitude of residual motion was almost ten times less than during nongated irradiation, and increases in the average effective dose rate by factors of 2.39-4.65, 2.39-4.59, 1.73-3.50, and 1.73-3.55 for the stBH, reBH, stSDBH, and reSDBH guiding maneuvers, respectively, were observed in contrast with conventional free breathing-based gated irradiation, depending on the respiratory-gated duty cycle settings. CONCLUSIONS: The proposed respiratory guidance method with personalized BFB was confirmed to be feasible in a group of volunteers. Increased effective dose rate and improved overall treatment precision were observed compared to conventional free breathing-based, respiratory-gated irradiation. Because breathing guidance curves could be established based on the respective average respiratory period and amplitude for each patient, it may be easier for patients to cooperate using this technique.