Solid

固体
  • 文章类型: Journal Article
    背景:腺泡细胞癌(AciCC)是一种罕见的临床实体和唾液腺恶性肿瘤。它与细胞形态学模式的广泛组织学变化有关。
    方法:对2002年至2023年诊断为AciCC的60例进行了不同细胞形态学模式的评估。
    结果:诊断时患者的平均年龄为44.35±16.8岁,范围为15至81岁。女性占58.3%,F:M比为1.4:1。53例(88.3%)发生在腮腺,鼻区2例(3.3%),软板和上唇各一例(1.7%)。其余三个案件的地点没有具体说明。最常见的主诉是与疼痛相关的明确定义的面部肿胀。平均肿瘤大小为3.8±1.9cm。最主要的建筑模式是固体(83.3%),其次是微囊(60%),然后是卵泡(41.7%),乳头状囊性(14.3%),和肾小管囊性(28.6%),在3例(5%)中报告了具有去分化/高级转化的AcyCC。在83.3%的病例中(60人中有50人),我们注意到两种或多种生长模式的混合。其他退行性改变包括突出的淋巴间质,出血,和囊性改变。
    结论:对AcCC的多种细胞形态学模式的认识和识别,特别是在发展中国家的机构中,高度特异性和敏感的免疫组织化学染色或分子诊断的可用性有限,是关键和必要的。
    BACKGROUND: Acinic cell carcinoma (AciCC) is a rare clinical entity and a salivary gland malignancy. It is associated with wide histological variations in the cytomorphological patterns.
    METHODS: Sixty cases diagnosed as AciCC from 2002 to 2023 were assessed for diverse cytomorphological patterns.
    RESULTS: The mean age of patients at the time of diagnosis was 44.35±16.8 years ranging from 15 to 81 years. Females comprised 58.3% for a F: M ratio of 1.4:1. Fifty three cases (88.3%) occurred in the parotid gland, two cases in the nasal region (3.3%), and one case each in the soft plate and upper lip (1.7%). The location of the remaining three cases was not specified. The most common presenting complaint was a well-defined facial swelling associated with pain. The average tumor size was 3.8±1.9 cm. The most predominant architectural pattern was solid (83.3%) followed by microcystic (60%), then follicular (41.7%), papillary cystic (14.3%), and tubulocystic (28.6%), and AciCC with de-differentiation/high-grade transformation was reported in three cases (5%). In 83.3% of the cases (50 out of 60), we noticed a mixture of two or more growth patterns. Other degenerative changes included prominent lymphoid stroma, hemorrhage, and cystic change.
    CONCLUSIONS: Awareness and recognition of diverse cytomorphological patterns of AciCC, especially in institutions of a developing country where there is limited availability of highly specific and sensitive immunohistochemical stains or molecular diagnostics, are crucial and essential.
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  • 文章类型: Journal Article
    本文主要介绍微控制器的软件开发领域,并详细介绍了嵌入式系统和物联网应用程序中现代编程实践和原则的实现。本文介绍了我们如何在微控制器上实现以前未实现的原则和应用的设计模式,以实现高质量的软件设计,它们目前仅用于在物联网参考模型的更高层上开发应用程序。提出了一种用于微控制器的自定义模块化框架,基于应用SOLID原则和适应微控制器应用程序开发需求的设计模式。所实现的框架实现了模块之间的独立通信和硬件组件的灵活集成。它的设计考虑了平台独立性,有助于其在不同开发环境中的广泛适应性和易用性。通过应用这些技术方法,我们可以创建应用程序,这些应用程序不仅在应用程序逻辑方面是可测试和可扩展的,而且还可以轻松适应这些硬件资源的变化。利用这些功能代表了一种创新的微控制器开发方法,从根本上提高了应用程序的长期可持续性和可扩展性。
    This article focuses on the area of software development for microcontrollers and details the implementation of modern programming practices and principles in embedded systems and IoT applications. This article explains how we implemented previously unimplemented principles and applied design patterns for quality software design on microcontrollers, which are currently only used for developing applications on the higher layers of the IoT reference model. A custom modular framework for microcontrollers is presented, based on applying SOLID principles and adapting design patterns specific to the microcontrollers\' application development needs. The implemented framework enables independent communication between modules and flexible integration of hardware components. It is designed with platform independence in mind, contributing to its wide adaptability and ease of use in diverse development environments. By applying these technological approaches, we can create applications that are not only testable and extensible in terms of application logic but also allow for easy adaptation to changes in these hardware resources. Utilizing these capabilities represents an innovative approach to development for microcontrollers that fundamentally improves the long-term sustainability and scalability of applications.
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  • 文章类型: Journal Article
    据报道,非主要或甚至最小的微乳头状和/或固体(MP/S)亚型对手术切除的肺腺癌(ADC)产生不利的预后影响。目前,缺乏证据证明高级病理亚型,包括MP/S组件,影响手术切除的肺ADC伴毛玻璃混浊(GGO)患者的预后。在这次调查中,我们探讨了GGO肺ADC中最少MP/S成分的预后意义。
    在2014年1月至2016年12月期间,对1,004例连续患者进行了回顾性队列研究,这些患者接受了病理分期(p期)I型肺ADC的治疗性切除,并在计算机断层扫描(CT)扫描上进行了GGO。将肿瘤分为MP/S阳性(MP/S+)组和MP/S阴性(MP/S-)组。当MP/S亚型占整个肿瘤的≥1%时,定义MP/S肿瘤。使用Kaplan-Meier分析评估MP/S亚型的预后影响,Cox比例风险模型和受限立方脊柱(RCS)模型。
    共发现86例(8.6%)MP/S+肿瘤和918例(91.4%)MP/S-肿瘤。MP/S+肿瘤的实体肿瘤直径和病理浸润性肿瘤大小均显著大于MP/S-肿瘤(13.0vs.4.0mm,P<0.001,18.0vs.10.0mm,分别为P<0.001)。经过7.3年的平均随访,MP/S成分的存在与RFS减少显著相关(5年RFS,MP/S+88.3%vs.MP/S-97.4%;P<0.001;HR=1.02)。在MP/S-(5年RFS,MP/S-Lep+98.0%vs.MP/S-Lep-95.3%;P=0.01;HR=0.89)和MP/S+亚组(5年RFS,MP/S+Lep+93.4%vs.MP/S+Lep-83.2%;P=0.10;HR=0.84)。根据多变量分析,MP/S+组分≥5%是唯一独立影响RFS的肿瘤相关因素[风险比(HR)=1.77;95%置信区间(CI):1.07-2.94]。如RCS模型所示,MP/S亚型的比例对RFS有逐渐的负面影响。
    I期GGO特征肺ADC中MP/S模式的存在具有重要的预后价值,可能对定制的术后治疗和监测策略有影响。特别是当比例超过整个肿瘤的5%时。
    UNASSIGNED: Non-predominant or even minimal micropapillary and/or solid (MP/S) subtypes have been reported to exert an unfavorable prognostic influence on surgically resected lung adenocarcinoma (ADC). Currently, there is a lack of evidence to demonstrate that high-grade pathological subtypes, including MP/S components, impact the prognosis of patients with surgically resected lung ADCs with ground-glass opacity (GGO). In this investigation, we explored the prognostic implications of minimal MP/S components in lung ADCs with GGO.
    UNASSIGNED: A retrospective cohort study was conducted on 1,004 consecutive patients undergoing curative resection for pathologic stage (p-stage) I lung ADCs featuring GGO on computed tomography (CT) scans between January 2014 and December 2016. Tumors were categorized into MP/S positive (MP/S+) group and MP/S negative (MP/S-) group. MP/S+ tumors were defined when MP/S subtypes constituted ≥1% of the entire tumor. The prognostic impact of MP/S subtypes was evaluated using Kaplan-Meier analysis, Cox proportional hazard model and restricted cubic spine (RCS) model.
    UNASSIGNED: A total of 86 (8.6%) cases with MP/S+ tumors and 918 (91.4%) cases with MP/S- tumors were identified. The solid component tumor diameter and pathological invasive tumor size of MP/S+ tumors were both significantly larger than that of MP/S- tumors (13.0 vs. 4.0 mm, P<0.001, and 18.0 vs. 10.0 mm, P<0.001, respectively). After a median follow-up of 7.3 years, the presence of MP/S components was significantly associated with decreased RFS (5-year RFS, MP/S+ 88.3% vs. MP/S- 97.4%; P<0.001; HR =1.02). The presence of a histologic lepidic (Lep) component demonstrated a prognostic advantage in both MP/S- (5-year RFS, MP/S-Lep+ 98.0% vs. MP/S-Lep- 95.3%; P=0.01; HR =0.89) and MP/S+ subgroups (5-year RFS, MP/S+Lep+ 93.4% vs. MP/S+Lep- 83.2%; P=0.10; HR =0.84). MP/S+ components ≥5% were the only tumor-related factor that independently affected RFS [hazard ratio (HR) =1.77; 95% confidence interval (CI): 1.07-2.94] according to multivariate analysis. There was a progressively negative impact of the proportion of MP/S subtypes on RFS as illustrated by RCS model.
    UNASSIGNED: The presence of MP/S patterns in stage I GGO-featured lung ADCs exhibit significant prognostic value and may have implications for tailored postoperative treatment and surveillance strategies, especially when the proportion exceeds 5% of the entire tumor.
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  • 文章类型: Journal Article
    背景:小尺寸(≤2cm)肺腺癌中微乳头状和实体亚型成分的鉴定在确定最佳手术程序中起着至关重要的作用。本研究旨在提出一种利用术前可用指标的直接预测方法。
    方法:自2019年1月至2022年7月,在宣武医院胸外科接受根治性切除术的小肺腺癌患者341例,对首都医科大学进行回顾性分析。根据固体或微乳头状成分是否≥5%(S/MP5和S/MP5-)将患者分为两组。单因素分析和多因素logistic回归分析用于确定S/MP5+的独立预测因子。然后构造一个列线图以直观地显示结果。最后,描绘了具有1000个自举重新采样的校准曲线和接收器工作特征(ROC)曲线以评估其性能。
    结果:根据术后病理结果,79例(23.2%)患者为S/MP5+,262例(76.8%)患者为S/MP5-。基于多变量分析,最大直径(p=0.010),合并肿瘤比率(CTR)(p<0.001)和全身免疫炎症指数(SII)(p<0.001)被确定为三个独立的危险因素,并纳入列线图。校准曲线显示S/MP5+的预测概率和实际概率之间的良好一致性。此外,该模型显示出一定的歧视,ROC曲线下面积为0.893。
    结论:基于SII构建的模型是预测小型肺腺癌术前高级别亚型成分的实用工具,有助于确定最佳手术方式。
    BACKGROUND: Identification of micropapillary and solid subtypes components in small-sized (≤ 2 cm) lung adenocarcinoma plays a crucial role in determining optimal surgical procedures. This study aims to propose a straightforward prediction method utilizing preoperative available indicators.
    METHODS: From January 2019 to July 2022, 341 consecutive patients with small-sized lung adenocarcinoma who underwent curative resection in thoracic surgery department of Xuanwu Hospital, Capital Medical University were retrospectively analyzed. The patients were divided into two groups based on whether solid or micropapillary components ≥ 5% or not (S/MP5+ and S/MP5-). Univariate analysis and multivariate logistic regression analysis were utilized to identify independent predictors of S/MP5+. Then a nomogram was constructed to intuitively show the results. Finally, the calibration curve with a 1000 bootstrap resampling and the receiver operating characteristic (ROC) curve were depicted to evaluate its performance.
    RESULTS: According to postoperative pathological results, 79 (23.2%) patients were confirmed as S/MP5+ while 262 (76.8%) patients were S/MP5-. Based on multivariate analysis, maximum diameter (p = 0.010), consolidation tumor ratio (CTR) (p < 0.001) and systemic immune-inflammation index (SII) (p < 0.001) were identified as three independent risk factors and incorporated into the nomogram. The calibration curve showed good concordance between the predicted and actual probability of S/MP5+. Besides, the model showed certain discrimination, with an area under ROC curve of 0.893.
    CONCLUSIONS: The model constructed based on SII is a practical tool to predict high-grade subtypes components of small-sized lung adenocarcinoma preoperatively and contribute to determine the optimal surgical approach.
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  • 文章类型: Journal Article
    由于低剂量螺旋计算机断层扫描的采用增加,越来越多的早期肺癌被诊断为恶性肺结节。但最大尺寸≤3cm的纯实体T1肺癌并不总是处于早期阶段,尽管它的尺寸很小。这种类型的癌症可以是高度侵袭性的,并且与病理相关,转移,术后复发,甚至死亡。然而,在临床上很容易误诊或延误诊断,从而对人类健康构成严重威胁。据报道,T1肺癌中淋巴结或胸腔外转移的百分比>20%。因此,了解和确定纯实体T1肺癌的侵袭性特征对于预防至关重要,诊断,和治疗策略,有利于改善预后。随着肺癌筛查的广泛开展,这些高侵袭性纯实体T1肺癌将成为未来主要的晚期肺癌。然而,关于如何识别这些“早期”侵袭性肺癌的精准医学信息有限。为临床医生提供新的见解,以早期识别和干预高侵袭性纯实体T1肺癌,本文综述了其临床特点,成像,病理学,基因改变,免疫微环境,多组学,以及当前的诊断和预测技术。
    A growing number of early-stage lung cancers presenting as malignant pulmonary nodules have been diagnosed because of the increased adoption of low-dose spiral computed tomography. But pure solid T1 lung cancer with ≤3 cm in the greatest dimension is not always at an early stage, despite its small size. This type of cancer can be highly aggressive and is associated with pathological involvement, metastasis, postoperative relapse, and even death. However, it is easily misdiagnosed or delay diagnosed in clinics and thus poses a serious threat to human health. The percentage of nodal or extrathoracic metastases has been reported to be >20% in T1 lung cancer. As such, understanding and identifying the aggressive characteristics of pure solid T1 lung cancer is crucial for prevention, diagnosis, and therapeutic strategies, and beneficial to improving the prognosis. With the widespread of lung cancer screening, these highly invasive pure solid T1 lung cancer will become the main advanced lung cancer in future. However, there is limited information regarding precision medicine on how to identify these \"early-stage\" aggressive lung cancers. To provide clinicians with new insights into early recognition and intervention of the highly invasive pure solid T1 lung cancer, this review summarizes its clinical characteristics, imaging, pathology, gene alterations, immune microenvironment, multi-omics, and current techniques for diagnosis and prediction.
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  • 文章类型: Published Erratum
    [这更正了文章DOI:10.3389/fonc.2021.792062。].
    [This corrects the article DOI: 10.3389/fonc.2021.792062.].
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  • 文章类型: Journal Article
    简介:牙源性肿瘤包括一组异质性病变,范围从错构瘤性病变到恶性肿瘤。组织学表现的显着变化可能会误导其准确的诊断和分类。成釉细胞瘤通常很容易理解并且易于诊断,但是自从Broca在1867年对牙源性肿瘤进行分类以来,分类系统一直在变化。多年来,它已被世界卫生组织修改,有许多补充和遗漏。这种动态变化是基于分子和遗传研究的结果和结论,最后一次修改是在2017年。病例报告:我们介绍了2例32岁和60岁女性报告面部肿胀,显示存在明显的组织病理学发现,并被诊断为成釉细胞瘤伴有牙样或腺样成釉细胞瘤。文献检索显示缺乏不同形式的成釉细胞瘤,这些成釉细胞瘤显示形成导管样结构和牙质。结论:由于缺乏相关研究和对患者的随访,生物学行为仍未被探索,因此强调此类病例很有趣。了解新实体的发病机制和组织病理学特征将有助于及时诊断,治疗计划和扩大病变范围。
    在线版本包含补充材料,可在10.1007/s12070-023-03534-6获得。
    Introduction: Odontogenic tumors encompass a heterogeneous group of lesions that range from hamartomatous lesions to malignancy. Considerable variation in histologic presentation can mislead their accurate diagnosis and categorization. Ameloblastoma is generally well understood and is easy to diagnose but there has been a constant change in the classification systems ever since Broca classified odontogenic tumors in the year 1867. Over the years, it has been modified by the World Health Organization with many additions and omissions. This dynamic change is based on the result and conclusions of molecular and genetic studies with the last modification in 2017. Case Report: We present two cases of females aged 32 and 60 years who reported with facial swellings, revealed the presence of distinct histopathological findings and were diagnosed as ameloblastoma with dentinoid or adenoid ameloblastoma. Literature search revealed dearth of distinct forms of ameloblastoma that show the formation of duct like structures and dentinoid. Conclusion: It is interesting to highlight such cases as the biological behavior is still unexplored due to paucity of relevant studies and follow up of patients. Understanding the pathogenesis and the histopathological characteristics of the newer entities will enable the prompt diagnosis, treatment plan and expanding the spectrum of the lesions.
    UNASSIGNED: The online version contains supplementary material available at 10.1007/s12070-023-03534-6.
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  • 文章类型: Journal Article
    在胰腺内可以发现一些实质性病变,主要来自外分泌和内分泌胰腺组织。在所有胰腺恶性肿瘤中,最常见的亚型是胰腺导管腺癌(PDAC),胰腺癌和PDAC可以互换使用。但是,除了PDAC,以及其他最常见和众所周知的实体病变,要么与良性疾病有关,比如胰腺炎,或者不是那么良性,如胰腺神经内分泌肿瘤(pNENs),有实质性胰腺病变被认为是罕见的,因为它们的发病率低。这些病变可能源自外分泌/内分泌以外的分化细胞系,例如来自神经鞘的胰腺神经鞘瘤或来自间充质细胞的孤立性纤维瘤。这些罕见的实体胰腺病变可能表现出良性至高度侵袭性恶性范围的行为。这篇综述包括胰腺内副脾的病例,胰腺结核,实性浆液性囊腺瘤,实性假乳头状瘤,胰腺神经鞘瘤,纯粹的导管内神经内分泌肿瘤,胰腺纤维孤立性肿瘤,腺泡细胞癌,具有破骨细胞样巨细胞的未分化癌,腺鳞癌,胰腺的胶体癌,原发性胰腺平滑肌肉瘤,原发性和继发性胰腺淋巴瘤和胰腺内转移。因此,重要的是要确定正确的诊断,以确保最佳的病人管理。因为它们的稀有性,他们的存在不太为人所知,当描绘时,在大多数情况下,顺便说一句,正确的诊断仍然具有挑战性。然而,在横截面成像模式上存在一些典型的成像特征,考虑到临床和生物学背景,大大有助于实现正确的诊断。
    Several solid lesions can be found within the pancreas mainly arising from the exocrine and endocrine pancreatic tissue. Among all pancreatic malignancies, the most common subtype is pancreatic ductal adenocarcinoma (PDAC), to a point that pancreatic cancer and PDAC are used interchangeably. But, in addition to PDAC, and to the other most common and well-known solid lesions, either related to benign conditions, such as pancreatitis, or not so benign, such as pancreatic neuroendocrine neoplasms (pNENs), there are solid pancreatic lesions considered rare due to their low incidence. These lesions may originate from a cell line with a differentiation other than exocrine/endocrine, such as from the nerve sheath as for pancreatic schwannoma or from mesenchymal cells as for solitary fibrous tumour. These rare solid pancreatic lesions may show a behaviour that ranges in a benign to highly aggressive malignant spectrum. This review includes cases of an intrapancreatic accessory spleen, pancreatic tuberculosis, solid serous cystadenoma, solid pseudopapillary tumour, pancreatic schwannoma, purely intraductal neuroendocrine tumour, pancreatic fibrous solitary tumour, acinar cell carcinoma, undifferentiated carcinoma with osteoclastic-like giant cells, adenosquamous carcinoma, colloid carcinoma of the pancreas, primary leiomyosarcoma of the pancreas, primary and secondary pancreatic lymphoma and metastases within the pancreas. Therefore, it is important to determine the correct diagnosis to ensure optimal patient management. Because of their rarity, their existence is less well known and, when depicted, in most cases incidentally, the correct diagnosis remains challenging. However, there are some typical imaging features present on cross-sectional imaging modalities that, taken into account with the clinical and biological context, contribute substantially to achieve the correct diagnosis.
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  • 文章类型: Multicenter Study
    腺样囊性癌(AdCC)是一种罕见的浸润性乳腺癌,预后良好。然而,有些案件具有侵略性。该研究旨在确定预后的临床病理预测因子。临床,放射学,记录了来自11个机构的76例AdCC病例的病理变量。以下组织学特征由每个机构的乳腺病理学家评估,包括诺丁汉等级(NG),各种生长模式的百分比(固体,cribriform,小梁管状),玄武岩成分的百分比,肿瘤边界(推挤,渗透),神经周浸润,淋巴管浸润,坏死,和离最近的边距的距离。评估了各种分级系统,包括NG,唾液腺型分级系统,和新的评分系统。新的分级系统纳入了增长模式(%固体,百分比筛形),基底细胞形态百分比,和有丝分裂计数使用Youden指数标准。所有变量均与无复发生存率相关。19名(25%)妇女出现局部和/或远处复发。在20例(26.3%)病例中发现了基底细胞形态(≥25%的肿瘤),在22例(28.9%)病例中发现了实体生长模式(使用≥60%的截止值)。在单变量分析中,以下变量与更差的无复发生存率显着相关:稳固的生长模式,玄武岩形态,淋巴管浸润,坏死,神经周浸润,和pN阶段。在包括基底细胞形态的多变量分析中,pN阶段,淋巴管浸润,和神经周浸润,基底动脉形态有统计学意义,风险比为3.872(95%CI,1.077;13.924;P=.038)。NG和新的分级系统都与无复发生存率相关。然而,在NG系统中,2级的风险与3级相似,在新的分级系统中,2级的风险与1级相似.对于固体生长模式和基底细胞形态,使用具有1个截止值的2层系统比具有2个截止值的3层系统更好。Basaloid形态和固体生长模式对AdCC具有预后价值,2层分级系统比3层系统表现更好。
    Adenoid cystic carcinoma (AdCC) is an uncommon type of invasive breast carcinoma with a favorable prognosis. However, some cases are aggressive. The study aims to define the clinicopathologic predictors of outcome. Clinical, radiological, and pathologic variables were recorded for 76 AdCC cases from 11 institutions. The following histologic characteristics were evaluated by the breast pathologist in each respective institution, including Nottingham grade (NG), percentages of various growth patterns (solid, cribriform, trabecular-tubular), percentage of basaloid component, tumor borders (pushing, infiltrative), perineural invasion, lymphovascular invasion, necrosis, and distance from the closest margin. Various grading systems were evaluated, including NG, salivary gland-type grading systems, and a new proposed grading system. The new grading system incorporated the growth pattern (percent solid, percent cribriform), percent basaloid morphology, and mitotic count using the Youden index criterion. All variables were correlated with recurrence-free survival. Nineteen (25%) women developed local and/or distant recurrence. Basaloid morphology (≥25% of the tumor) was identified in 20 (26.3%) cases and a solid growth pattern (using ≥60% cutoff) in 22 (28.9%) cases. In the univariate analysis, the following variables were significantly correlated with worse recurrence-free survival: solid growth pattern, basaloid morphology, lymphovascular invasion, necrosis, perineural invasion, and pN-stage. In the multivariate analysis including basaloid morphology, pN-stage, lymphovascular invasion, and perineural invasion, basaloid morphology was statistically significant, with a hazard ratio of 3.872 (95% CI, 1.077; 13.924; P =.038). The NG and the new grading system both correlated with recurrence-free survival. However, grade 2 had a similar risk as grade 3 in the NG system and a similar risk as grade 1 in the new grading system. For solid growth patterns and basaloid morphology, using a 2-tier system with 1 cutoff was better than a 3-tier system with 2 cutoffs. Basaloid morphology and solid growth pattern have prognostic values for AdCC, with a 2-tier grading system performing better than a 3-tier system.
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  • 文章类型: Journal Article
    未经证实:据报道,实性显性腺癌(SPA)是肺腺癌(LUAD)中预后差、化疗和靶向治疗反应不理想的一种亚型。然而,潜在的机制在很大程度上仍然未知,免疫治疗对SPA的适用性尚未得到研究.
    UNASSIGNED:我们对1078例未经治疗的LUAD患者进行了多组学分析,基因组,转录组,以及来自公共和内部队列的蛋白质组数据,以确定SPA的不良预后和差异治疗反应的潜在机制,并研究SPA的免疫治疗潜力。在我们中心接受新辅助免疫疗法的LUAD患者队列中进一步证实了免疫疗法对SPA的适用性。
    未经证实:随着其侵袭性的临床病理行为,SPA具有显著较高的肿瘤突变负荷(TMB)和改变的通路数量,降低TTF-1和Napsin-A的表达,与非实体优势腺癌(非SPA)相比,更高的增殖评分和更强的免疫抗性微环境,考虑到其预后较差。此外,SPA具有显著较低的治疗靶向驱动突变频率和较高的EGFR/TP53共突变频率,这与对EGFR酪氨酸激酶抑制剂的抗性有关。表明靶向治疗的可能性较低。同时,SPA富集了与化疗反应不良相关的分子特征(较高的化学持久性特征评分,较低的化疗反应特征评分,缺氧微环境,TP53突变的频率更高)。相反,muti-omics谱分析显示,SPA具有更强的免疫原性,并富集了免疫治疗的阳性生物标志物(更高的TMB和T细胞受体多样性;更高的PD-L1表达和更多的免疫细胞浸润;更高的基因突变频率预测有效的免疫治疗,和免疫疗法相关基因标签的表达升高)。此外,在接受新辅助免疫疗法的LUAD患者队列中,SPA的病理消退率高于非SPA,有主要病理反应的患者在SPA中富集,证实SPA更容易对免疫疗法有反应。
    UNASSIGNED:与非SPA相比,SPA富集了与不良预后相关的分子特征,化疗和靶向治疗反应不理想,对免疫疗法反应良好,表明更适合免疫疗法,而不适合化疗和靶向治疗。
    Solid predominant adenocarcinoma (SPA) has been reported to be a subtype with poor prognosis and unsatisfactory response to chemotherapy and targeted therapy in lung adenocarcinoma (LUAD). However, the underlying mechanisms remain largely unknown and the suitability of immunotherapy for SPA has not been investigated.
    We conducted a multi-omics analysis of 1078 untreated LUAD patients with clinicopathologic, genomic, transcriptomic, and proteomic data from both public and internal cohorts to determine the underlying mechanisms of poor prognosis and differential therapeutic responses of SPA and to investigate the potential of immunotherapy for SPA. The suitability of immunotherapy for SPA was further confirmed in a cohort of LUAD patients who received neoadjuvant immunotherapy in our center.
    Along with its aggressive clinicopathologic behaviors, SPA had significantly higher tumor mutation burden (TMB) and number of pathways altered, lower TTF-1 and Napsin-A expression, higher proliferation score and a more immunoresistant microenvironment than non-solid predominant adenocarcinoma (Non-SPA), accounting for its worse prognosis. Additionally, SPA had significantly lower frequency of therapeutically targetable driver mutations and higher frequency of EGFR/TP53 co-mutation which was related to resistance to EGFR tyrosine kinase inhibitors, indicating a lower potential for targeted therapy. Meanwhile, SPA was enriched for molecular features associated with poor response to chemotherapy (higher chemoresistence signature score, lower chemotherapy response signature score, hypoxic microenvironment, and higher frequency of TP53 mutation). Instead, muti-omics profiling revealed that SPA had stronger immunogenicity and was enriched for positive biomarkers for immunotherapy (higher TMB and T cell receptor diversity; higher PD-L1 expression and more immune cell infiltration; higher frequency of gene mutations predicting efficacious immunotherapy, and elevated expression of immunotherapy-related gene signatures). Furthermore, in the cohort of LUAD patients who received neoadjuvant immunotherapy, SPA had higher pathological regression rates than Non-SPA and patients with major pathological response were enriched in SPA, confirming that SPA was more prone to respond to immunotherapy.
    Compared with Non-SPA, SPA was enriched for molecular features associated with poor prognosis, unsatisfactory response to chemotherapy and targeted therapy, and good response to immunotherapy, indicating more suitability for immunotherapy while less suitability for chemotherapy and targeted therapy.
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