Anaplastic thyroid cancer (ATC) is an aggressive endocrine malignancy characterized by rapid progression and limited therapeutic options. Ferritinophagy, a selective autophagic process mediated by NCOA4, regulates intracellular iron homeostasis. Here, we demonstrate that the prolyl isomerase Pin1 drives ATC progression by suppressing NCOA4-dependent ferritinophagy. Mechanistically, Pin1 recognizes phosphorylated NCOA4 through its substrate-binding WW domain. CDK2 phosphorylates NCOA4 at Ser572, creating a binding site for Pin1. This interaction promotes K29/K48-linked polyubiquitination and proteasomal degradation of NCOA4, thereby blocking ferritinophagy, lowering intracellular Fe²⁺ and lipid peroxidation, and ultimately suppressing ferroptosis. Pin1 knockdown or treatment with the pharmacological Pin1 inhibitor KPT-6566 stabilizes NCOA4, enhances ferritinophagy, and triggers ferroptosis, markedly restraining ATC growth both in vitro and in vivo. These findings identify Pin1 as a previously unrecognized suppressor of ferroptosis through NCOA4-dependent ferritinophagy and support Pin1 inhibition as a potential therapeutic strategy for ATC.

Breast cancer is a common and highly malignant, currently, HIST1H4C was found to be associated with several human malignancies. The purpose of this study is to investigate tissue HIST1H4C expression in breast cancer and explore its role in disease progression and its interaction with neoadjuvant therapy efficacy. we analyzed tissue HIST1H4C mRNA expression in BC tissue samples from 105 patients received with neoadjuvant therapy using qPCR between 2019 and 2022. Statistical analysis showed that a high expression of HIST1H4C before neoadjuvant therapy was positively related to good responder (CR + PR), while high expression of HIST1H4C after neoadjuvant therapy was negatively related good responder. And HIST1H4C expression was significantly decreased in patients with good responder. In addition, high HIST1H4C expression was also related to ER negative, PR negative, high KI67 expression, high level of histological grade, large tumor size and more lymph node metastases in Curtis database. Furthermore, high HIST1H4C expression before and after-treatment in our center or in database has a positively correlation with poor prognosis. HIST1H4C is the potential biomarker of neoadjuvant therapy and prognosis for breast cancer.

As an emerging biomarker, tumor mutational burden (TMB) has attracted increasing attention from clinicians in predicting the efficacy of tumor immunotherapy. Currently, TMB is detected primarily by whole-exome sequencing or targeted panel sequencing on high-throughput sequencing platforms. However, the lack of uniformity in detection methods, threshold settings, and reporting formats, as well as the significant differences in TMB values among different cancer types, have hindered the standardized application of this biomarker in clinical practice. This consensus focuses on the definition, standardization of detection, clinical significance, and limitations of TMB, and provides consensus recommendations for the clinical application of TMB in real-world practice in China. This consensus is aimed at helping clinicians and laboratory personnel understand the clinical significance and testing standards of TMB, promoting more accurate interpretation of test results, and improving patient care.

Nuclear protein in testis (NUT) carcinoma (NC) represents a rare, clinically aggressive cancer defined by pathognomonic NUT Midline Carcinoma Family Member 1 (NUTM1) gene fusions, with bromodomain and extraterminal domain (BET) protein 4 (BRD4)-NUTM1 being the predominant oncogenic driver. Since its description in 1991, gradual advances have clarified the pathologic mechanisms of NC and its diagnostic methods; however, NC treatment remains a significant challenge. Moreover, diagnostic and treatment approaches for this cancer require further validation and standardization. These guidelines were developed by the Chinese Alliance of Research for NC (ChARN) based on current evidence in the literature and incorporate consensus-based input from multiple international experts. They provide comprehensive guidance on NC diagnosis and treatment, covering epidemiology, pathogenesis, diagnostic methods, therapeutic strategies, BET-inhibitor toxicity, palliative care, and prognostic assessment during follow-up. They also emphasize the importance of multidisciplinary team collaboration in NC treatment and recommend prioritizing enrollment in prospective clinical trials for patients. Current mainstays of treatment include surgical resection, radiotherapy, and medical treatment (chemotherapy, targeted therapy, and immunotherapy), although no standard treatment protocol exists. Future research directions include improving diagnostic efficiency, exploring new therapeutic strategies (such as highly selective BET inhibitors, BET-inhibitor combinations, and PROTAC technologies), and recommending basket trials as a research approach for patients with NUTM1 gene fusions.

Purpose: This study aimed to develop and evaluate a deep learning model that directly analyzes three-dimensional automated breast ultrasound videos (DL-3DABUV) to assist breast cancer diagnosis, and to examine the optimal reading mode for clinical implementation.Methods: This retrospective study included 547 patients (285 benign, 262 malignant), who were randomly assigned to a training set (n=437) and a test set (n=110). The DL-3DABUV model, built using ResNet50 and multi-instance learning, was trained by directly analyzing videos without image selection or manual annotation. Six radiologists (three experienced and three novice) evaluated the test set under three modes: independent-reading (without DL-3DABUV), second-reading (without prior knowledge of DL-3DABUV results), and concurrent-reading (after viewing DL-3DABUV results). The diagnostic performance of DL-3DABUV, experienced radiologists, and novice radiologists was compared. Reading times across the three modes were also assessed.Results: Compared to experienced radiologists in independent reading, DL-3DABUV showed no significant differences in area under the receiver operating characteristic curve (AUC) (0.82 vs. 0.83), sensitivity (82.1% vs. 81.6%), or specificity (81.5% vs. 88.3%) (all P>0.05). DL-3DABUV exhibited higher AUC and specificity than novice radiologists in independent-reading (0.82 vs. 0.68, P<0.001; 81.5% vs. 57.4%, P<0.001). However, novice performance reached parity with DL-3DABUV in both second-reading and concurrent-reading. No significant differences in diagnostic performance were observed between second-reading and concurrent-reading. Concurrent reading significantly reduced reading time by 33.6 seconds compared with second-reading (P<0.001).Conclusion: DL-3DABUV achieves diagnostic performance comparable to experienced radiologists and enhances diagnostic accuracy for novices. Concurrent reading provides a more efficient workflow by reducing reading time while maintaining diagnostic performance.

Abstract Background The aim of this study was to conduct an in silico analysis of a novel compound heterozygous variant in breast cancer susceptibility gene 2 (BRCA2) to clarify its structure–function relationship and elucidate the molecular mechanisms underlying triple-negative breast cancer (TNBC). Methods A tumor biopsy sample was obtained from a 42-year-old Chinese woman during surgery, and a maxBRCA™ test was conducted using the patient’s whole blood. We obtained an experimentally determined 3D structure (1mje.pdb) of the BRCA2 protein from the Protein Data Bank (PDB) as a relatively reliable reference. Subsequently, the wild-type and mutant structures were predicted using SWISS-MODEL and AlphaFold, and the accuracy of these predictions was assessed through the SAVES online server. Furthermore, we utilized a high ambiguity-driven protein–protein docking (HADDOCK) algorithm and protein–ligand interaction profiler (PLIP) to predict the pathogenicity of the mutations and elucidate pathogenic mechanisms that potentially underlies TNBC. Results Histological examination revealed that the tumor biopsy sample exhibited classical pathological characteristics of TNBC. Furthermore, the maxBRCA™ test revealed two compound heterozygous BRCA2 gene mutations (c.7670 C > T.pA2557V and c.8356G > A.pA2786T). Through performing in silico structural analyses and constructing of 3D models of the mutants, we established that the mutant amino acids valine and threonine were located in the helical domain and oligonucleotide binding 1 (OB1), regions that interact with DSS1. Conclusion Our analysis revealed that substituting valine and threonine in the helical domain region alters the structure and function of BRCA2 proteins. This mutation potentially affects the binding of proteins and DNA fragments and disrupts interactions between the helical domain region and OB1 with DSS1, potentially leading to the development of TNBC. Our findings suggest that the identified compound heterozygous mutation contributes to the clinical presentation of TNBC, providing new insights into the pathogenesis of TNBC and the influence of compound heterozygous mutations in BRCA2.

Purpose breast cancer is a common and highly malignant, currently, HIST1H4C was found to be associated with several human malignancies. The purpose of this study is to investigate tissue HIST1H4C expression in breast cancer and explore its role in disease progression and its interaction with neoadjuvant therapy efficacy. Methods we analyzed tissue HIST1H4C mRNA expression in BC tissue samples from 105 patients received with neoadjuvant therapy using qPCR between 2019–2022. Results Statistical analysis showed that a high expression of HIST1H4C before neoadjuvant therapy was positively related to good responder (CR + PR), while high expression of HIST1H4C after neoadjuvant therapy was negatively related good responder. And HIST1H4C expression was significantly decreased in patients with good responder. In addition, high HIST1H4C expression was also related to ER negative, PR negative, high KI67 expression, high level of histological grade, large tumor size and more lymph node metastases in Curtis database. Furthermore, high HIST1H4C expression before and after-treatment in our center or in database has a positively correlation with poor prognosis. Conclusions HIST1H4C is the potential biomarker of neoadjuvant therapy and prognosis for breast cancer.

The fusion genes NRG1 and NRG2, members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, NRG1 retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of NRG1 gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting NRG1 and NRG2 gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying NRG1-positive patients. Currently, there are no approved targeted drugs for NRG1 and NRG2. Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

To elucidate the role of microRNA-1284 (miR-1284) in the onset of thyroid cancer (TC) and its underlying mechanism. Differential expressions of miR-1284 in TC and thyroid tissues were detected. Regulatory effects of miR-1284 on proliferative, migratory, apoptotic potentials and cell cycle progression were assessed. In addition, miR-1284 levels in TC tissues and peripheral blood of TC patients were determined as well. Through collecting culture medium and exosomes of PTC cells, changes in miR-1284 levels were examined. MiR-1284 was downregulated in TC than normal thyroid tissues. Overexpression of miR-1284 attenuated proliferative and migratory potentials, but induced apoptosis in TPC-1 and FTC-133 cells. Moreover, overexpression of miR-1284 upregulated E-cadherin and downregulated N-cadherin in papillary TC (PTC) cells. MiR-1284 was downregulated in TC tissues, while its level in the peripheral blood of TC patients was upregulated. Besides, miR-1284 was upregulated in the culture medium and exosomes of PTC cells, which was reversed by Brefeldin A treatment. Overexpression of miR-1284 suppresses proliferative and migratory potentials and induces apoptosis in TC. Upregulated miR-1284 in the peripheral blood of TC patients may be derived from exosomes secreted by PTC cells.

Internationally, the outbreak of coronavirus disease 2019 (COVID-19) has become the most serious public health emergency.With the adjustment of the prevention and control policies, China downgraded the management of COVID-19 from Class A to Class B, causing new challenges in the clinical management of patients with breast cancer.It is necessary to formulate clinical strategies for timely and reasonable anti-tumor treatment after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.By combing the relevant evidence and summarizing the anti-tumor treatment experience for breast cancer patients with SARS-CoV-2 infection in various regions, the expert panel of the Breast Cancer Professional Committee of the Chinese Society of Clinical Oncology (CSCO-BC) discussed and voted on hot and difficult issues of this situation timely.Based on the vote results, combined with domestic and foreign guidelines and consensus, the key points of treatment and management of breast cancer patients who were infected with COVID-19 have been established to provide suggestions and recommendations for clinical practice, such as restart time of anti-tumor treatment, application of anti-tumor drugs and other considerations.In the formulation of this key point, we mainly focus on mild to moderate and asymptomatic infection patients who account for the largest proportion of COVID-19 patients, and propose diagnosis and treatment recommendations for breast cancer patients with different infections and after SARS-CoV-2 infection, aiming to provide a reference for clinical diagnosis and treatment.

目的 探讨模拟门诊教学模式在医学生皮肤见习课中培养学生人文素质的重要性及实际应用效果.方法 选取参与2019年3—5月临床见习的本科生86人,按班级分为对照组(n=42)和试验组(n=44),对照组仅给予常规的见习教学,试验组除了给予常规的见习教学外,额外应用模拟门诊的教学模式,以培养学生的人文素养.分别于见习课前、学期末,通过教师点评、学生自评及同学互评三种评分方式,评价学生接诊患者的能力,以评定学生的人文素质水平.随后,通过理论课考核成绩、问卷调查等方式,获知学生对教师及教学方法的满意度.结果 见习课前,两组学生接诊患者能力的评分比较差异无统计学意义(P>0.05);见习课后,相比对照组,试验组学生获得更高的教师评分、学生自评及同学互评分,差异有统计学意义(P<0.001),且试验组学生的评分优于见习前,差异有统计学意义(P<0.001),对照组学生的评分则未见显著性提升,差异无统计学意义(P>0.05);学期末的理论考试成绩,两组对比差异无统计学意义(P>0.05),但试验组的课堂活跃度、学生对教师、教学方式的满意度均高于对照组,差异有统计学意义(P<0.001).结论 医学生的培养是一项长期、缓慢、耗时耗力的工程,学生人文素质的培养至关重要,仅给予理论教学是远远不够的.模拟门诊教学模式是一项很好的尝试,在实践中促进学生学习的主观能动性,利于培养提升医学生的人文素质.

[This corrects the article DOI: 10.3389/fonc.2019.00569.].

Objectives—To investigate the clinical characteristics, managements, outcome, and evaluate the risk factors of Multisystem (MS) Langerhans Cell Histiocytosis (LCH) with diverse skin lesions as the first sign in four young infants. Methods—Their clinical features, disease progression, therapy, and outcomes were reviewed and analyzed retrospectively. Results—The average onset age of skin lesions was about 2 months. Cases 1 and 2 had risk organs involved (RO+) and a lack of bone lesions, and progression could not be reversed by systemic chemotherapy. They both died eventually. Cases 3 and 4 (RO–) had bone involvement and were given systemic chemotherapy for a prolonged duration. Unluckily, Case 3 had a recurrence 2 years later, while Case 4’s recurrence happened nearly one year later, and diabetes insipidus one and a half years later. They both survived and are still in remission. Conclusion—MS-LCH infants with a low age of the first presentation in the skin are prone to dissemination, while RO+ is associated with high mortality. In addition, bone involvement may be a protective factor. Immunohistochemical examination of skin tissue facilitates correct early diagnosis, and adequate follow-up is necessary.

Since the end of February 2022, China has experienced a new wave of coronavirus disease 2019 (COVID-19) outbreaks caused by the Omicron variant. These outbreaks frequently occur at multiple sites, involving many provinces and cities. Prevention and control work is facing more challenges only after the Wuhan epidemic. As a general principle, the priority of treatment should be determined according to the biological features, clinical stages, and treatment stages of different breast cancer (BC) subtypes, and individualized diagnosis and treatment recommendations should be given. These patients belong to a high-priority population, for whom receiving treatment in a hospital is urgently required. In addition, treatment should also be prioritized for patients experiencing new tumor-related symptoms or serious adverse events. If the disease condition is stable, the frequency of follow-up re-examinations can be reduced according to the epidemic control situation. Online diagnosis and treatment are recommended to maintain doctor-patient communication. However, special attention should still be paid to treatment-associated safety issues, and safety monitoring measures should be adopted. For low-priority patients with stable disease, elective follow-up visits may be arranged after risk-benefit assessment based on the severity of the local COVID-19 epidemic and the risk of infection. Based on the above principle, we once again present our opinions on the top ten hot issues concerning the clinical diagnosis and treatment of BC during the COVID-19 epidemic in China.

Background: Melanoma is the most lethal skin tumor. PARP1 plays an oncogenic role in tumors, but the mechanism of PARP1 in melanoma remains unclear. Explicating the functional mechanism of PARP1 might highlight new targets for improving the survival rate of melanoma patients. Methods: First, the expression level of PARP1 and its correlation with prognosis of melanoma were examined by the TCGA dataset, GEO12391 dataset, and western blot. Then, the differentially expressed genes (DEGs) after PARP1 intervention were screened by microarray slides. Also, Gene Set Enrichment Analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of DEGs were performed. At the same time, these DEGs were further compared with PARP1-related DEGs in GEO59455, and correlation analysis was performed on the intersection genes to screen PARP1 target genes. Finally, the relationship between PARP1 and its target gene was examined by western blot analysis and reverse transcription-quantitative (RT-q) PCR. CCK8 assay was used to determine the biological role of PARP1 and its target gene in melanoma. The data that support the findings of this study come from the open databases, which are acknowledged at the end of the manuscript. Results: We demonstrated that PARP1 was overexpressed in melanoma and melanoma cell lines, and upregulated expression of PARP1 was associated with higher pathological stages and unfavorable prognosis of melanoma. Five genes, including NFATc2, ITGAX, CYP26B1, SYT17, and VGF, were screened as PARP1 target genes, and NFATc2 was confirmed to be regulated by PARP1. Further CCK8 assay showed that downregulation of PARP1 or NFATc2 expression could inhibit melanoma proliferation. Conclusions: Taken together, this study demonstrated that PARP1 was a prognostic marker and contributed to melanoma proliferation through the regulation of NFATc2.

Gene fusions can drive tumor development for multiple types of cancer. Currently, many drugs targeting gene fusions are being approved for clinical application. At present, tyrosine receptor kinase (TRK) inhibitors targeting neurotrophic tyrosine receptor kinase (NTRK) gene fusions are among the first "tumor agnostic" drugs approved for pan-cancer use. Representative TRK inhibitors, including larotrectinib and entrectinib, have shown high efficacy for many types of cancer. At the same time, several second-generation drugs designed to overcome first-generation drug resistance are undergoing clinical development. Due to the rarity of NTRK gene fusions in common cancer types and technical issues regarding the complexity of fusion patterns, effectively screening patients for TRK inhibitor treatment in routine clinical practice is challenging. Different detection methods including immunohistochemistry, fluorescence in situ hybridization, reverse transcription-polymerase chain reaction, and (DNA and/or RNA-based) next-generation sequencing have pros and cons. As such, recommending suitable tests for individual patients and ensuring the quality of tests is essential. Moreover, at present, there is a lack of systematic review for the clinical efficacy and development status of first- and second-generation TRK inhibitors. To resolve the above issues, our expert group has reached a consensus regarding the diagnosis and treatment of NTRK gene fusion solid tumors, aiming to standardize clinical practice with the goal of benefiting patients with NTRK gene fusions treated with TRK inhibitors.