Discover. Oncology最新文献

Background: Immune checkpoint blockade (ICB) therapy, including antibodies targeting the programmed cell death protein 1 (PD-1) pathway, has significantly prolonged the overall survival (OS) in patients with advanced cervical cancer (CC). ICB treatment affects both target cells and various components released by immune cells, which can be observed in peripheral blood. However, there has been limited research on the dynamics of peripheral blood immunophenotyping and its association with OS in CC patients receiving ICB therapy.

Methods: Patients with persistent, recurrent, or metastatic CC treated with ICB were enrolled between December 2019 and September 2022. The dynamic changes in peripheral blood immune cells, immunoglobulins, and complement components were analyzed at baseline (within 30 days prior to the first ICB cycle) and after the second cycle of ICB treatment (4-6 weeks after the first ICB treatment). Associations of the baseline levels of peripheral blood immune cells, immunoglobulins, complement components with OS were analyzed using multivariable Cox regression analysis.

Results: In this retrospective cohort study, 119 patients who received at least two cycles of ICB were included. Data on peripheral blood immune cells, immunoglobulins, and complement components were available for 70 of these patients. The percentages of suppressor T (Ts) cells and natural killer (NK) cells in peripheral blood increased significantly post-ICB treatment, whereas the Th/Ts ratio and IgM levels decreased. The percentages of cytotoxic T (Tc) cells, Ts cells, the Th/Ts ratio, and levels of IgM, IgA, C3, and C4 were significantly associated with the OS of patients. Furthermore, multivariable Cox regression analysis found that a high level of IgA was associated with poor OS of the patients (HR = 2.918; 95% CI, 1.081-7.877, P = 0.035).

Conclusion: Our study demonstrated the potential proliferation of peripheral blood anti-tumor T cells in some CC patients undergoing ICB therapy. The observed associations between peripheral blood immunophenotyping and OS suggest that these biomarkers might have potential as prognostic tools.

Lung cancer is one of the deadliest malignancies worldwide, with distant metastasis being a major cause of death. However, the specific mechanisms of lung cancer metastasis remain unclear. NcRNAs, a widely present type of non-coding RNAs in the body, constitute about 98% of the human genome, lacking protein-coding capacity but involved in various cellular processes such as proliferation, apoptosis, invasion, and migration. Studies have shown that ncRNAs play a crucial role in the metastasis of lung cancer, although research in this area is limited. This review summarizes the biological origins and functions of ncRNAs, their specific roles and mechanisms in lung cancer metastasis, and discusses their potential for early screening and therapeutic applications in lung cancer. Furthermore, it outlines the challenges in translating basic advancements of ncRNAs in lung cancer metastasis into clinical practice.

Background: Liver cancer is a common second primary cancer in gastric cancer patients, but whether a gastric cancer diagnosis contributes to the development of second primary liver cancer remains contentious. This study aims to utilize Mendelian randomization (MR) analysis to investigate the potential causal relationship between gastric cancer and second primary liver cancer from a genetic perspective.

Methods: We extracted single nucleotide polymorphism for gastric cancer and liver cancer in the East Asian population from the Genome-Wide Association Studies database as instrumental variables and employed univariate and multivariate MR analysis to evaluate the causal relationship between gastric cancer and liver cancer. The robustness of the findings was ensured through heterogeneity and sensitivity analyses.

Results: Univariate MR analysis revealed that genetic susceptibility to gastric cancer in the East Asian population was significantly associated with an increased risk of liver cancer [Inverse-variance weighted (IVW): OR = 1.252, 95% CI 1.076-1.457, P = 0.004]. Multivariate MR analysis indicated that after adjusting for confounding factors, the significant positive causal relationship between gastric cancer and liver cancer remained robust (all P < 0.05). Furthermore, no causal relationship was observed between liver cancer diagnosis and the development of gastric cancer in the East Asian population (IVW: OR = 1.111, 95% CI 0.936-1.318, P = 0.228).

Conclusion: Genetic prediction results suggest that gastric cancer survivors might face an increased risk of developing second primary liver cancer, implying the potential value of routine liver cancer screening for gastric cancer survivors.

Purpose: In this work, we propose to develop a 3D U-Net-based deep learning model that accurately predicts the dose distribution for breast cancer radiotherapy.

Methods: This study included 176 breast cancer patients, divided into training, validating and testing sets. A deep learning model based on the 3D U-Net architecture was developed to predict dose distribution, which employed a double encoder combination attention (DECA) module, a cross stage partial + Resnet + Attention (CRA) module, a difficulty perception and a critical regions loss. The performance and generalization ability of this model were evaluated by the voxel mean absolute error (MAE), several clinically relevant dosimetric indexes and 3D gamma passing rates.

Results: Our model accurately predicted the 3D dose distributions with each dosage level mirroring the clinical reality in shape. The generated dose-volume histogram (DVH) matched with the ground truth curve. The total dose error of our model was below 1.16 Gy, complying with clinical usage standards. When compared to other exceptional models, our model optimally predicted eight out of nine regions, and the prediction errors for the first planning target volume (PTV1) and PTV2 were merely 1.03 Gy and 0.74 Gy. Moreover, the mean 3%/3 mm 3D gamma passing rates for PTV1, PTV2, Heart and Lung L achieved 91.8%, 96.4%, 91.5%, and 93.2%, respectively, surpassing the other models and meeting clinical standards.

Conclusions: This study developed a new deep learning model based on 3D U-Net that can accurately predict dose distributions for breast cancer radiotherapy, which can improve the quality and planning efficiency.

Background: Immunotherapy is an effective treatment for BRAF V600E-mutant colorectal cancer, but currently, only a few benefit from it. Therefore, exploring new immunotherapy strategies is essential.

Methods: We obtained RNA sequencing data and clinical information of colorectal cancer patients from the TCGA and GEO databases. The impact of the BRAF V600E mutation on tumor microenvironment characteristics, gene expression, and signaling pathways was evaluated using bioinformatics approaches. Weighted gene co-expression network analysis (WGCNA) were used to identify core genes associated with T cell dysfunction. Consensus clustering was applied for subtype construction. Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest (RF) algorithms were employed to filter potential immunotherapy targets.

Results: We found that BRAF V600E mutation has a complex impact on the immune profile of colorectal cancer. It increases immune cell infiltration and activates immune-related signaling pathways, yet it also severely restricts T cell function. We subsequently identified 39 core genes associated with T cell dysfunction and constructed subtypes of BRAF V600E colorectal cancer based on their expression profiles. Significant heterogeneity was observed between these subtypes in immune signaling pathway activity, immune infiltration patterns, immune phenotype scores, and mechanisms of resistance to immunotherapy. Ultimately, using machine learning algorithms and bioinformatics validation, we identified IDO1 as a potential immunotherapy targets for BRAF V600E-mutant colorectal cancer.

Conclusion: This study constructed novel T cell dysfunction molecular subtypes for BRAF V600E-mutant colorectal cancer and identified IDO1 as a potential immunotherapy target, providing a new strategy for immunotherapy.

Capicua transcriptional repressor (CIC)-rearranged sarcoma (CRS) is a rare and highly aggressive malignant soft tissue small round cell sarcoma. Most CRS tumors occur in the soft tissues of the limbs and trunk and cases in the thyroid gland are extremely rare, with no extant reports in an adult thyroid. This report aims to familiarize clinicians and pathologists with CRS in the thyroid gland, thereby helping them identify new cases, and provide pathological evidence for comprehensive diagnosis and treatment. A 30-year-old woman presented with an asymptomatic right thyroid mass of 5 months. Neck ultrasonography revealed a hypoechoic hypervascular nodule with a maximum diameter of 5 cm. The noncalcified nodule was classified as Ti-RADS 4a. Besides thyroid dysfunction, her thyroglobulin and anti-thyroid peroxidase antibody concentrations were 35.83 IU/mL and > 1,000.00 IU/mL, respectively. CRS was diagnosed based on the histomorphology, immunohistochemistry, and molecular genetics results. The patient opted for further treatment at Zhejiang Cancer Hospital. Ten months after surgical removal, positron emission tomography/computed tomography revealed tumor metastasis to the cervical lymph nodes and lungs. In February 2023, the patient underwent postoperative adjuvant radiotherapy for the tumor bed and cervical lymph nodes and received doses of PGTVtb 6,000 cGy/30F/DT and PTV 5,400 cGy/30F/DT. The patient last visited the clinic in May 2024 due to fever, fatigue, diarrhea, and other symptoms. CRS in solid organs is extremely rare; however, when the morphology shows multinodular, small, round cells with mild-to-moderate atypia, vacuolated nuclei, and prominent nucleoli, it should be considered as a potential differential diagnosis.

This research explored the role of microRNA (miRNA)-21 in prostate cancer (PCa) cells, as well as its regulation of the JAK/STAT pathway in PCa cells. Quantitative real-time PCR was employed to examine miRNA-21 expression in PCa cells. Cell viability and proliferation were detected by MTT and colony formation assays. Cell migration was measured by wound healing and transwell assays. The janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway-related protein expression was detected using western blot. The results indicated that miRNA-21 was significantly up-regulated in PCa cells, and inhibition of miRNA-21 suppressed the viability, proliferation and migration of PCa cells. Besides, inhibition of miRNA-21 lessened the levels of JAK/STAT pathway-related proteins in both PCa cells. Additionally, Ruxolitinib treatment (an inhibitor of the JAK/STAT pathway) could reverse the elevated cell viability and proliferation in miRNA-21 mimics-transfected PCa cells. Taken together, our study demonstrates that miRNA-21 promotes the migration and proliferation of PCa cells via activating the JAK /STAT pathway.

Colorectal cancer (CRC) was the third most common cause of mortality associated with cancer globally. miR-124-3p has been widely acknowledged for its pivotal role as a tumor suppressor in various malignancies. In this study, we aimed to investigate the specific functions and underlying mechanisms of miR-124-3p in CRC cell proliferation, migration and invasion. A comprehensive set of assays, including CCK-8, colony formation, wound healing assays, flow cytometry, RT-qPCR and Western blotting, were conducted to assess the impact of miR-124-3p expression on CRC cell growth. Our investigations into miR-124-3p and its potential target gene ITGB1 were facilitated through bioinformatics analysis and dual-luciferase reporter assays. To further solidify our findings, rescue experiments were executed to validate the role of miR-124-3p in regulating the proliferation, migration, and apoptosis of CRC cells, genes involving Wnt/β-catenin signaling pathway were also detected. Our study revealed that the overexpression of miR-124-3p significantly suppressed both the proliferation and migratory capabilities of CRC cells, while its downregulation had the opposite effect. Notably, ITGB1 was identified as a putative target gene of miR-124-3p, exhibiting an inverse correlation with the expression levels of miR-124-3p. Moreover, the overexpression of ITGB1 was able to abrogate the inhibitory effects exerted by miR-124-3p overexpression on CRC cell proliferation, migration, and Wnt1/β-catenin protein levels. Our results reveal that miR-124-3p targets ITGB1 to regulate CRC cell proliferation and migration may be associated with the Wnt/β-catenin signaling pathway. These findings provide that a miR-124-3p/ITGB1 axis may be a potential target for the treatment of CRC.