Technology in Cancer Research & Treatment最新文献

Background: Breast cancer is a prevalent public health concern affecting numerous women globally and is associated with palmitoylation, a post-translational protein modification. Despite increasing focus on palmitoylation, its specific implications for breast cancer prognosis remain unclear. The work aimed to identify prognostic factors linked to palmitoylation in breast cancer and assess its effectiveness in predicting responses to chemotherapy and immunotherapy.

Methods: We utilized the "limma" package to analyze the differential expression of palmitoylation-related genes between breast cancer and normal tissues. Hub genes were identified using the "WGCNA" package. Using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis, we identified a prognostic feature associated with palmitoylation and developed a prognostic nomogram with the "regplot" package. The predictive values of the model for chemotherapy and immunotherapy responses were assessed using immunophenoscore (IPS) and the "pRophetic" package.

Results: We identified 211 differentially expressed genes related to palmitoylation, among which 44 demonstrated prognostic potential. Subsequently, a predictive model comprising eleven palmitoylation-related genes was developed. Patients were classified into high-risk and low-risk groups based on the median risk score. The findings revealed that individuals in the high-risk group exhibited lower survival rates, while those in the low-risk group showed increased immune cell infiltration and improved responses to chemotherapy and immunotherapy. Moreover, the BC-Palmitoylation Tool website was established.

Conclusion: This study developed the first machine learning-based predictive model for palmitoylation-related genes and created a corresponding website, providing clinicians with a valuable tool to improve patient outcomes.

The programmed cell death protein 1 (PD-1, CD279) is an important therapeutic target in many oncological diseases. This checkpoint protein inhibits T lymphocytes from attacking other cells in the body and thus blocking it improves the clearance of tumor cells by the immune system. While there are already multiple FDA-approved anti-PD-1 antibodies, including nivolumab (Opdivo^® from Bristol-Myers Squibb) and pembrolizumab (Keytruda^® from Merck), there are ongoing efforts to discover new and improved checkpoint inhibitor therapeutics. In this study, we present multiple anti-PD-1 antibody fragments that were derived computationally using protein diffusion and evaluated through our scalable, in silico pipeline. Here we present nine synthetic Fv structures that are suitable for further empirical testing of their anti-PD-1 activity due to desirable predicted binding performance.

Purpose: This study aims to investigate the influence of the magnetic field on treatment plan quality using typical phantom test cases, which encompass a circle target test case, AAPM TG119 test cases (prostate, head-and-neck, C-shape, multi-target test cases), and a lung test case.

Materials and methods: For the typical phantom test cases, two plans were formulated. The first plan underwent optimization in the presence of a 1.5 Tesla magnetic field (1.5 T plan). The second plan was re-optimized without a magnetic field (0 T plan), utilizing the same optimization conditions as the first plan. The two plans were compared based on various parameters, including con-formity index (CI), homogeneity index (HI), fit index (FI) and dose coverage of the planning target volume (PTV), dose delivered to organs at risk (OARs) and normal tissue (NT), monitor unit (MU). A plan-quality metric (PQM) scoring procedure was employed. For the 1.5 T plans, dose verifications were performed using an MR-compatible ArcCHECK phantom.

Results: A smaller dose influence of the magnetic field was found for the circle target, prostate, head-and-neck, and C-shape test cases, compared with the multi-target and lung test cases. In the multi-target test case, the significant dose influence was on the inferior PTV, followed by the superior PTV. There was a relatively large dose influence on the PTV and OARs for lung test case. No statistically significant differences in PQM and MUs were observed. For the 1.5 T plans, gamma passing rates were all higher than 95% with criteria of 2 mm/3% and 2 mm/2%.

Conclusion: The presence of a 1.5 T magnetic field had a relatively large impact on dose parameters in the multi-target and lung test cases compared with other test cases. However, there were no significant influences on the plan-quality metric, MU and dose accuracy for all test cases.

Objective: To investigate the effect of various frequencies of bolus use on the superficial dose of volumetric modulated arc therapy after modified radical mastectomy for breast cancer.

Methods: Based on the computed tomography images of a female anthropomorphic breast phantom, a 0.5 cm silicone-based 3D-printed bolus was created. Nine points evenly distributed on the breast skin were selected for assessing the skin dose, and a volume of subcutaneous lymphatic drainage of the breast (noted as ROI2-3) was delineated for assessing the chest wall dose. The treatment plans with and without bolus (plan_wb and plan_nb) were separately designed using the prescription of 50 Gy in 25 fractions following the standard dose constraints of the adjacent organ at risk. To characterize the accuracy of treatment planning system (TPS) dose calculations, the doses of the nine points were measured five times by thermoluminescence dosimeters (TLDs) and then were compared with the TPS calculated dose.

Results: Compared with Plan_nb (144.46 ± 10.32 cGy), the breast skin dose for plan_wb (208.75 ± 4.55 cGy) was significantly increased (t = -18.56, P < 0.001). The deviation of skin dose was smaller for Plan_wb, and the uniformity was significantly improved. The calculated value of TPS was in good agreement with the measured value of TLD, and the maximum deviation was within 5%. Skin and ROI2-3 doses were significantly increased with increasing frequencies of bolus applications. The mean dose of the breast skin and ROI2-3 for 15 and 23 times bolus applications were 45.33 Gy, 50.88 Gy and 50.36 Gy, 52.39 Gy, respectively.

Conclusion: 3D printing bolus can improve the radiation dose and the accuracy of the planned dose. Setting Plan_wb to 15 times for T1-3N+ breast cancer patients and 23 times for T4N+ breast cancer patients can meet the clinical need. Quantitative analysis of the bolus application frequency for different tumor stages can provide a reference for clinical practice.

Background: Gastric intestinal metaplasia(GIM) is an independent risk factor for GC, however, its pathogenesis is still unclear. Ferroptosis is a new type of programmed cell death, which may be involved in the process of GIM. The purpose of this study was to analyze the expression of ferroptosis-related genes (FRGs) in GIM tissues and to explore the relationship between ferroptosis and GIM.

Method: The results of GIM tissue full transcriptome sequencing were downloaded from Gene Expression Omnibus(GEO) database. R software (V4.2.0) and R packages were used for screening and enrichment analysis of differentially expressed genes(DEGs). The key genes were screened by least absolute shrinkage and selection operator(LASSO) and support vector machine-recursive feature elimination(SVM-RFE) algorithm. Receiver operating characteristic(ROC) curve was used to evaluate the diagnostic efficacy of key genes in GIM. Clinical samples were used to further validate hub genes.

Results: A total of 12 differentially expressed ferroptosis-related genes (DEFRGs) were identified. Using two machine learning algorithms, GOT1, ALDH3A2, ACSF2 and SESN2 were identified as key genes. The area under ROC curve (AUC) of GOT1, ALDH3A2, ACSF2 and SESN2 in the training set were 0.906, 0.955, 0.899 and 0.962 respectively, and the AUC in the verification set were 0.776, 0.676, 0.773 and 0.880, respectively. Clinical samples verified the differential expression of GOT1, ACSF2, and SESN2 in GIM.

Conclusion: We found that there was a significant correlation between ferroptosis and GIM. GOT1, ACSF2 and SESN2 can be used as diagnostic markers to effectively identify GIM.

There are no standard third-line or beyond treatments for patients with driver mutation-positive advanced lung adenocarcinoma (LUAD). Anlotinib was approved as a third-line multitarget drug in China in 2018. Limited data are available regarding the efficacy and safety of anlotinib compared with chemotherapy. To investigate the efficacy and safety of anlotinib compared with traditional chemotherapy in patients with epidermal growth factor receptor (EGFR)-positive advanced LUAD. We conducted a retrospective study of 83 EGFR mutation-positive patients with advanced LUAD between 2011 and 2022. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints, whereas the objective response rate (ORR) and disease control rate (DCR) were the secondary endpoints. Anlotinib-related adverse events (AEs) were recorded to evaluate the safety of anlotinib. 39 patients with LUAD received anlotinib and 44 patients with LUAD received chemotherapy were enrolled in the study. Patients treated with anlotinib exhibited longer PFS (11.2 vs 4.5 months, P < .01) and OS (18.8 vs 15.8 months, P < .05) than patients treated with chemotherapy. There were no significant differences in ORR (7.9% vs 20.5%, P = .129) or DCR (100% vs 93.2%, P = .120) between the two groups. Anlotinib-related AEs grading 3-4 level were observed in 2 (5.1%) patients, no anlotinib-related death was recorded. Cox regression analyses of PFS and OS showed that brain metastases and age < 30 years at diagnosis had negative effects on clinical outcomes. Anlotinib is effective and safe in patients with EGFR-positive advanced LUAD. Patients without brain metastases had better clinical outcomes.

Liver cancer a leading cause of cancer-related deaths worldwide, yet understanding of its development mechanism remains limited, and treatment barriers present substantial challenges. Owing to the heterogeneity of tumors, traditional 2D culture models are inadequate for capturing the complexity and diversity of tumor biology and understanding of the disease. Organoids have garnered considerable attention because of their ability to self-renew and develop functional structures in vitro that closely resemble those of human organs. This review explores the history of liver organoids, their cellular origins, techniques of constructing tumor microenvironments that recapitulate liver cancer organoids, and the biological and clinical applications of liver and liver cancer organoids and explores the current challenges related to liver cancer organoid applications and potentially valuable solutions, with the aim of facilitating the construction of in vitro clinical models of liver cancer therapeutic research.

Objectives: We retrospectively analyzed the next-generation sequencing (NGS) results from diagnosed NSCLC patients to identify and compare genomic alterations of NSCLC between Moroccan patients and the Cancer Genome Atlas (TCGA). We also aimed to investigate the distribution and frequency of concurrent genomic alterations.

Methods: From December 2022 to December 2023, a retrospective study of 76 formalin-fixed paraffin-embedded (FFPE) samples have been profiled using the Oncomine™ Precision Assay on the Ion Torrent™ Genexus™ Integrated Sequencer across the panel of 50 key genes that are applicable for the selection of targeted therapy.

Results: Seventy of the 76 FFPE sequenced samples carried at least one genetic alteration in the tested genes. The study identified 234 genetic alterations in 18 genes. Targetable genetic alterations in EGFR, KRAS, MET, BRAF, ALK, RET and ROS1 were identified in 84.3% of tumors. EGFR and KRAS mutations were frequently reported, occurring in 24.3% and 22.9% of cases, respectively. The untargetable genetic alterations were found in 74.3% of the specimens in FGFR3, TP53, ERBB2, PIK3CA, CDKN2A, PDL1, FGFR1, PTEN, CHEK2 and ERBB3. There were additional uncommon/rare mutations in EGFR, BRAF, RET and ROS1. Comparing the prevalence of selected mutated genes in the NSCLC patients from the TCGA database identified substantial differences in EGFR (24.3%, vs14.97%), KRAS (22.9%, vs 25.99%), and TP53 (34.3%, vs 50.94%). ALK, ROS1, and RET gene rearrangements were detected in 4.3% of the 70 tumors tested. The ALK/RET/MET/ROS1/EML4 fusions were detected in 11.4% of samples. Co-alterations occurred in 67.1% of specimens. Co-occurring driver gene mutations were observed in 44.3%. TP53 mutations co-occurred driver gene mutations in 30% of tumors. Three cases (4.3%) harbored concurrent FGFR3, TP53, and PIK3CA alterations.

Conclusion: Our results regarding the proportion of samples with actionable mutations demonstrate the value of NGS testing for NSCLC patients in a real-world clinical diagnostic setting.

To investigate the differences in serum tryptophan, lysine, and phenylalanine levels in breast cancer patients, the correlation between the three amino acids with the chemotherapy regimen, and their significance in the clinical diagnosis and treatment of breast cancer.Clinical data were collected from the Department of Breast Surgery at Yunnan Cancer Hospital, encompassing 216 cases from July to December 2020, including 91 healthy individuals, 38 with benign tumors, and 87 with cancer. Amino acid levels were measured using liquid chromatography-tandem mass spectrometry. Statistical analyses, such as the Kruskal-Wallis H-test and Wilcoxon test, were conducted to compare the levels of these amino acids across the healthy group, benign tumor group, and breast cancer group. The χ2 test and Fisher's exact probability method were employed to assess the relationship between amino acid levels and breast cancer stage, grade, and chemotherapy regimen.The results indicated that there were significant differences in serum lysine (H = 36.13, P < .001) and phenylalanine (H = 34.03, P < .001) levels among the three groups. However, tryptophan levels did not show statistically significant variances. Specifically, lysine and phenylalanine levels were significantly different when comparing the healthy group with the breast cancer group and the benign tumor group with the breast cancer group. These differences were not significant when comparing the healthy group with the benign tumor group. Furthermore, there were no statistically significant distinctions observed in lysine (F = 0.836, P > .05) and phenylalanine (F = 1.466, P > .05) levels across different conventional chemotherapy regimens among the breast cancer cases studied.Serum lysine and phenylalanine levels might serve as potential biomarkers for breast cancer, and the choice of chemotherapy regimen is unlikely to impact significant changes in these amino acid levels.