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Pulmonary artery choriocarcinoma mimicking pulmonary thromboembolism: a case report. 肺动脉绒毛膜癌模拟肺血栓栓塞:1例报告。
IF 1.5 4区 医学 Q4 ONCOLOGY Pub Date : 2024-12-31 Epub Date: 2024-12-27 DOI: 10.21037/tcr-2024-2461
Shifang Yang, Zhidan Tan, Manzhi Zhao, Xinglin Gao, Hiren J Mehta, Kim Styrvoky, Bryan S Benn, Sylvia S Yong, Bin Li

Background: Primary choriocarcinoma of the pulmonary artery is an exceedingly rare malignant neoplasm, which is often misdiagnosed due to its nonspecific clinical presentation. While this condition is characterized by the presence of trophoblastic cells, typically associated with gestational trophoblastic diseases, we encountered a case occurring in an extragenital location. The rarity of such tumors makes it challenging for clinicians to consider them in differential diagnosis, especially when the initial symptoms mimic more common conditions such as pulmonary thromboembolism (PTE).

Case description: We present a clinical case of a 32-year-old female with suspected PTE, attributed to severe cough, hemoptysis, chest pain, oral contraceptive use, and a pulmonary artery filling defect observed on computed tomography pulmonary angiography (CTPA). The patient was treated with standard anticoagulation therapy; however, there was no improvement in the clinical condition. A biopsy was subsequently performed, leading to the histopathologic diagnosis of primary pulmonary artery choriocarcinoma with the presence of malignant trophoblastic cells within the pulmonary artery. The patient underwent chemotherapy and achieved complete remission within a 1-year follow-up period, as confirmed by β-human chorionic gonadotropin (β-HCG) tests and imaging examinations showing marked improvement.

Conclusions: This case underscores the importance of early recognition and accurate diagnosis of primary pulmonary artery choriocarcinoma, a condition that can be easily overlooked due to its rarity and deceptive clinical presentation. Timely diagnosis is crucial for the initiation of appropriate treatment, such as chemotherapy, which in this instance, contributed to the patient's survival. This report highlights the need for heightened clinical suspicion and the use of invasive diagnostic procedures in cases where the clinical picture is atypical and does not respond to standard therapeutic interventions.

背景:原发性肺动脉绒毛膜癌是一种非常罕见的恶性肿瘤,由于其非特异性临床表现而经常被误诊。虽然这种情况的特点是滋养细胞的存在,通常与妊娠滋养细胞疾病有关,但我们遇到了一个发生在生殖器外部位的病例。这类肿瘤的罕见性使得临床医生很难在鉴别诊断中考虑到它们,特别是当最初的症状与肺血栓栓塞(PTE)等更常见的疾病相似时。病例描述:我们报告一个32岁女性疑似PTE的临床病例,由于严重咳嗽,咯血,胸痛,口服避孕药,并在肺血管造影(CTPA)上观察到肺动脉充盈缺陷。患者接受标准抗凝治疗;然而,临床情况没有改善。随后进行活检,组织病理学诊断为原发性肺动脉绒毛膜癌,肺动脉内存在恶性滋养细胞。患者接受化疗,随访1年完全缓解,经β-人绒毛膜促性腺激素(β-HCG)检测及影像学检查均有明显改善。结论:该病例强调了早期识别和准确诊断原发性肺动脉绒毛膜癌的重要性,由于其罕见和临床表现不真实,这种疾病很容易被忽视。及时诊断对于开始适当的治疗至关重要,例如化疗,在这种情况下,化疗有助于患者的生存。本报告强调,在临床表现不典型且对标准治疗干预无效的病例中,需要加强临床怀疑和使用侵入性诊断程序。
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引用次数: 0
Targeting the EZH2-SLFN11 pathway-a lesson in developing molecularly-informed treatments for recurrent small cell lung cancer. 靶向EZH2-SLFN11通路——开发复发性小细胞肺癌分子治疗的经验教训
IF 1.5 4区 医学 Q4 ONCOLOGY Pub Date : 2024-12-31 Epub Date: 2024-12-25 DOI: 10.21037/tcr-24-1755
Fangdi Sun, Millie S Das
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引用次数: 0
FOXF2 may inhibit esophageal squamous cell carcinoma growth and metastasis by regulating the EZR-ERBB2 axis. FOXF2可能通过调控EZR-ERBB2轴抑制食管鳞状细胞癌的生长和转移。
IF 1.5 4区 医学 Q4 ONCOLOGY Pub Date : 2024-12-31 Epub Date: 2024-12-27 DOI: 10.21037/tcr-2024-2365
Zhen-Yu Hu, Wei-Hao Deng, Wei-Jie Cai, Xian-Yu Qin, Hao-Sheng Zheng, Jian Tan, Xiao-Long Jiang, Yu-Zhen Zheng, Hong-Ying Liao

Background: FOXF2, a member of the transcription factor FOX family proteins, plays a key role in tumorigenesis and tumor aggressiveness. However, the potential molecular mechanism of FOXF2 in esophageal squamous cell carcinoma (ESCC) remains largely unknown. Exploring its role and mechanism in ESCC progression may help identify new diagnostic markers and therapeutic targets. The aim of this study is to investigate the potential functions of the FOXF2 gene within the context of ESCC and to elucidate the underlying molecular pathways involved.

Methods: Using the GoMiner database, GeneCard database, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and the COMPARTMENTS subcellular localization database, we identified the most likely downstream molecule of the FOXF2 gene, EZR; the subcellular locations of FOXF2 and EZR; the possible biological pathways [Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG)]; and the protein interactions networks of the EZR gene enriched from the OMICS datasets via Metascape. We also used The Cancer Genome Atlas database to analyze the correlation between EZR and ERBB signaling pathway. In addition, we verified the RNA and protein expression of the target genes using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Furthermore, we employed Western blot analysis and plasmid transfection and lentiviral infection techniques to gene edit FOXF2 and EZR in different EC cells to obtain stable overexpression or knockdown of the cell lines. This was followed by ex vivo and in vivo experiments including migration assay, cell scratch assay, clone formation assay, and a xenotransplantation mouse model to validate the functional phenotype of the gene-edited cells.

Results: We found that knockdown of FOXF2 expression significantly enhanced the growth, invasion, and metastasis of ESCC cells both in vitro and in vivo. Moreover, we demonstrated that FOXF2 was predominantly expressed in the nucleus and directly interacted with EZR, thereby inhibiting EZR transcriptional expression, resulting in suppressed ERBB2 signal function, ultimately halting ESCC growth and metastasis.

Conclusions: Taken together, these results reveal the tumor-suppressive functions of FOXF2 in inhibiting EZR-mediated ERBB2 activation, suggesting that FOXF2 could serve as a potential novel predicting prognostic biomarker for ESCC.

背景:FOXF2是转录因子FOX家族蛋白的一员,在肿瘤发生和肿瘤侵袭性中起关键作用。然而,FOXF2在食管鳞状细胞癌(ESCC)中的潜在分子机制在很大程度上仍然未知。探索其在ESCC进展中的作用和机制可能有助于确定新的诊断标志物和治疗靶点。本研究的目的是研究FOXF2基因在ESCC中的潜在功能,并阐明所涉及的潜在分子途径。方法:利用GoMiner数据库、GeneCard数据库、Search Tool for Retrieval of Interacting Genes/Proteins (STRING)数据库和COMPARTMENTS亚细胞定位数据库,鉴定出FOXF2基因最可能的下游分子EZR;FOXF2和EZR的亚细胞位置;可能的生物学途径[基因本体(GO)和京都基因与基因组百科全书(KEGG)];以及通过metscape从组学数据集中富集的EZR基因的蛋白质相互作用网络。我们还利用The Cancer Genome Atlas数据库分析了EZR与ERBB信号通路的相关性。此外,我们使用实时定量逆转录聚合酶链反应(qRT-PCR)验证了目标基因的RNA和蛋白质表达。此外,我们利用Western blot分析、质粒转染和慢病毒感染技术对不同EC细胞中的FOXF2和EZR进行基因编辑,获得稳定的过表达或低表达细胞系。随后进行离体和体内实验,包括迁移实验、细胞划痕实验、克隆形成实验和异种移植小鼠模型,以验证基因编辑细胞的功能表型。结果:我们发现FOXF2表达的下调在体外和体内均能显著促进ESCC细胞的生长、侵袭和转移。此外,我们发现FOXF2主要在细胞核中表达,并直接与EZR相互作用,从而抑制EZR的转录表达,从而抑制ERBB2信号功能,最终阻止ESCC的生长和转移。综上所述,这些结果揭示了FOXF2在抑制ezr介导的ERBB2激活方面的肿瘤抑制功能,提示FOXF2可能作为一种潜在的预测ESCC预后的新型生物标志物。
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引用次数: 0
Diagnostic accuracy of folate receptor-positive circulating tumor cells in differentiating between benign and malignant pulmonary nodules. 叶酸受体阳性循环肿瘤细胞鉴别肺良恶性结节的诊断准确性。
IF 1.5 4区 医学 Q4 ONCOLOGY Pub Date : 2024-12-31 Epub Date: 2024-12-27 DOI: 10.21037/tcr-2024-2493
Guo-Feng Wu, Rong-Chao Chen, Jing Luo, Ming-Tai Li, Pei Yu, Pan-Xiao Shen, Jia-Ying Luo, Yin-Yin Qin
<p><strong>Background: </strong>Currently, traditional blood biomarkers such as neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCA) etc. are mostly elevated in the late stage of tumour, and patients have already lost the chance of tumour eradication when the relevant indexes are found to be elevated. Therefore, there is a need for blood biomarkers with higher sensitivity, better specificity, and better accessibility. Folate receptor-positive circulating tumor cells (FR<sup>+</sup>CTCs) may have diagnostic value in lung cancer. Nevertheless, there is a scarcity of research exploring the efficacy of FR<sup>+</sup>CTCs in screening pulmonary nodules for lung cancer. The aims of this study were to differentiate between lung cancer and benign pulmonary nodules using FR<sup>+</sup>CTCs in conjunction with blood markers and to develop a composite diagnostic model for pulmonary nodules.</p><p><strong>Methods: </strong>Based on the inclusion and exclusion guidelines, we retrospectively analysed 1,135 patients with pulmonary nodules who underwent tissue biopsy or surgical resection after FR<sup>+</sup>CTC testing, assessed the histopathological findings by a specialised pathologist, and collected and compared demographic characteristics, blood markers, imaging and pathological parameters in malignant and benign patients. The random forest model was used to screen for indicators and to establish a composite index of blood biomarkers. The performance of single factors or the integrated model were estimated by applying receiver operating characteristic (ROC) analysis.</p><p><strong>Results: </strong>A total of 612 patients were included in the lung cancer group, predominantly presenting with stage I adenocarcinomas (n=458). The median age was 54 years, and 43.1% of the patients were male. In comparison, 523 patients were included in the benign pulmonary nodules group, with a median age of 53 years and 46.8% male. No significant differences were identified between the two groups with regard to gender or age (P>0.05). The level of FR<sup>+</sup>CTCs in the lung cancer group was significantly higher than that in the benign nodule group (P<0.001). The white blood cell (WBC) and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) levels were significantly higher in the lung cancer group than in the benign nodule group (P<0.001 and P=0.01, respectively). FR<sup>+</sup>CTC level was associated with the pathological subtype (P=0.02), WBC (P<0.001), and lactate dehydrogenase (LDH) level (P=0.01). In both groups, the FR<sup>+</sup>CTC level was higher in the single-nodule group than in the multiple-nodule group (P=0.002 and P=0.040, respectively). The diagnostic sensitivity and specificity of FR<sup>+</sup>CTCs for lung cancer at a cutoff of 8.7 FU/3 mL was 61.9% and 75.0%, respectively. Increasing the cutoff to 1.5 times (13.1 FU/3 mL) and 2 times (17.4 FU/3 mL) improved the specificity to 90.8% and 95.6%, respectively. T
背景:目前,传统的血液生物标志物如神经元特异性烯化酶(NSE)、癌胚抗原(CEA)、鳞状细胞癌抗原(SCCA)等多在肿瘤晚期升高,当发现相关指标升高时,患者已经失去了肿瘤根除的机会。因此,需要具有更高灵敏度、更好特异性和更好可及性的血液生物标志物。叶酸受体阳性循环肿瘤细胞(FR+ ctc)可能对肺癌有诊断价值。然而,关于FR+ ctc筛查肺癌肺结节的有效性的研究还很缺乏。本研究的目的是利用FR+ ctc结合血液标志物来区分肺癌和良性肺结节,并建立肺结节的复合诊断模型。方法:根据纳入和排除指南,我们回顾性分析了1135例在FR+CTC检测后接受组织活检或手术切除的肺结节患者,由专业病理学家评估组织病理学结果,并收集和比较恶性和良性患者的人口统计学特征、血液标志物、影像学和病理参数。采用随机森林模型筛选指标,建立血液生物标志物综合指数。采用受试者工作特征(receiver operating characteristic, ROC)分析评价单因素或综合模型的疗效。结果:肺癌组共纳入612例患者,主要表现为I期腺癌(n=458)。中位年龄54岁,男性占43.1%。良性肺结节组523例,中位年龄53岁,男性46.8%。两组在性别和年龄方面无显著差异(P < 0.05)。肺癌组FR+CTC水平明显高于良性结节组(P+CTC水平与病理亚型相关(P=0.02),单结节组WBC (P+CTC水平分别高于多结节组(P=0.002和P=0.040)。在8.7 FU/3 mL的临界值下,FR+ ctc对肺癌的诊断敏感性和特异性分别为61.9%和75.0%。将临界值提高到1.5倍(13.1 FU/3 mL)和2倍(17.4 FU/3 mL),特异性分别提高到90.8%和95.6%。FR+ ctc联合WBC、降钙素原、LDH的曲线下面积为0.976[95%可信区间(CI): 0.910-1.000],敏感性为100.0%,特异性为85.7%。结论:FR+CTC被证明是一种可行的血液生物标志物,有助于肺癌的早期检测。基于FR+CTC的联合模型在肺结节患者中显示出比任何单一生物标志物更高的准确性。
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引用次数: 0
KIF18A and CDK1 as combined therapeutic targets in cervical and endometrial carcinomas: based on bioinformatics analysis and in vitro experiments. KIF18A和CDK1联合治疗宫颈癌和子宫内膜癌:基于生物信息学分析和体外实验
IF 1.5 4区 医学 Q4 ONCOLOGY Pub Date : 2024-12-31 Epub Date: 2024-12-18 DOI: 10.21037/tcr-24-1831
Mengjie Wang, David Lukanovic, Fabio Barra, Aoli Lei

Background: Chromosomal instability (CIN) has been identified as a factor that increases the susceptibility of tumor cells to kinesin family member 18A (KIF18A) inhibitors. Limited research exists on genes that are associated with sensitization to KIF18A inhibitors (KIF18Ais). Our study aimed to identify a gene linked to heightened sensitivity to KIF18Ais in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) and uterine corpus endometrial carcinoma (UCEC).

Methods: The Cancer Genome Atlas (TCGA) and X2K Appyter databases were used to analyze potential kinases associated with KIF18A-related genes in CESC and UCEC. In vitro assessments, such as Cell Counting Kit-8 (CCK-8), transwell, and terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assays, were performed to evaluate the combined effects of KIF18A and cyclin-dependent kinase 1 inhibitors (CDK1is) in CESC and UCEC cell lines.

Results: Our findings indicated that the combination of KIF18A with kinases may potentially augment the efficacy of KIF18Ais, given its close involvement in cell cycle and chromosome segregation. Through bioinformatics analysis, we observed a significant up-regulation of CDK1 expression in CESC and UCEC, which exhibited a strong correlation with KIF18A expression. Our hypothesis regarding the potential of CDK1 as a combination therapeutic target for KIF18A was supported by our cell experiments, which demonstrated that inhibition of CDK1 notably increased the sensitivity of CESC and UCEC cells to KIF18Ais. The combined use of CDK1is and KIF18Ais exhibited a synergistic effect in inhibiting cell migration and inducing apoptosis in CESC and UCEC cells.

Conclusions: This study provides evidence that targeting both KIF18A and CDK1 exerts synergistic anti-tumor effects in CESC and UCEC via inhibiting cell proliferation and migration and inducing apoptosis, suggesting a promising therapeutic strategy for these cancers.

背景:染色体不稳定性(CIN)已被确定为增加肿瘤细胞对激酶家族成员18A (KIF18A)抑制剂易感性的一个因素。关于与KIF18A抑制剂(KIF18Ais)致敏相关的基因的研究有限。我们的研究旨在鉴定一个与宫颈鳞状细胞癌、宫颈内膜癌(CESC)和子宫内膜癌(UCEC)中KIF18Ais敏感性增高相关的基因。方法:利用肿瘤基因组图谱(TCGA)和X2K Appyter数据库分析CESC和UCEC中kif18a相关基因的潜在激酶。体外评估,如细胞计数试剂盒-8 (CCK-8)、transwell和末端脱氧核苷酸转移酶介导的缺口末端标记(TUNEL)检测,用于评估KIF18A和细胞周期蛋白依赖性激酶1抑制剂(CDK1is)在CESC和UCEC细胞系中的联合作用。结果:我们的研究结果表明,鉴于KIF18A与细胞周期和染色体分离密切相关,KIF18A与激酶的结合可能潜在地增强KIF18Ais的功效。通过生物信息学分析,我们发现CDK1在CESC和UCEC中表达显著上调,且与KIF18A表达有很强的相关性。我们的细胞实验支持了我们关于CDK1可能作为KIF18A联合治疗靶点的假设,实验表明,抑制CDK1显著增加了CESC和UCEC细胞对KIF18Ais的敏感性。CDK1is和KIF18Ais联合使用在CESC和UCEC细胞中显示出抑制细胞迁移和诱导细胞凋亡的协同作用。结论:本研究提供证据表明,靶向KIF18A和CDK1可通过抑制细胞增殖和迁移以及诱导细胞凋亡,在CESC和UCEC中发挥协同抗肿瘤作用,为CESC和UCEC提供了一种有前景的治疗策略。
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引用次数: 0
Multi-slice computed tomography radiomics combined with serum alpha-L-fucosidase: a potential biomarker for precise identification of pleomorphic adenoma and Warthin tumor. 多层计算机断层扫描放射组学联合血清α - l -聚焦酶:一种精确识别多形性腺瘤和沃辛瘤的潜在生物标志物。
IF 1.5 4区 医学 Q4 ONCOLOGY Pub Date : 2024-12-31 Epub Date: 2024-12-27 DOI: 10.21037/tcr-24-871
Qinghan Yan, Lingzi Liao, Xin Wang, Xianlin Zeng, Leyang Zhang, Dengqi He

Background: The rising incidence of parotid gland tumors, with a focus on pleomorphic adenomas (PMA) and Warthin tumors (WT), necessitates accurate preoperative distinction due to their treatment variability and PMA's malignant potential. Traditional imaging, while valuable, has limited accuracy. This study employs multi-slice computed tomography (MSCT) radiomics coupled with serum alpha-L-fucosidase (AFU) levels to develop a diagnostic model aimed at elevating clinical discernment and precision therapy delivery.

Methods: Ninety-one patients were randomly assigned to one of two cohorts: training or validation, at a ratio of 7:3 (64 vs. 27). The region of interest (ROI) on each tumor from the collected MSCT images was delineated to extract radiomics features. In the training cohort, the least absolute shrinkage and selection operator (LASSO) regression and 5-fold cross-validation were adopted to screen the extracted features and calculate Rad-score. Four diagnostic models were developed after univariate and multivariate logistic regression analysis of Rad-score and clinical factors. The performance of four models was then evaluated in the validation cohort by the comparison of receiver operating characteristic (ROC) curve and calibration curve to select the best one. Finally, the clinical application value of the best model was assessed via the nomogram and decision curve analysis (DCA) curve.

Results: Multivariate logistic regression analysis revealed serum AFU, Rad-score and gender as independent diagnostic factors for PMA and WT distinguishment. The nomogram combining the three factors had an area under the curve (AUC) of 0.934 [95% confidence interval (CI): 0.863-1.000] and 0.987 (95% CI: 0.956-1.000) in the training and validation cohorts, respectively, with great goodness-of-fit and clinical value.

Conclusions: The optimized nomogram combining MSCT radiomics and AFU improved the accuracy of distinguishing PMA from WT, suggesting its potential for developing new biomarkers.

背景:腮腺肿瘤的发病率不断上升,尤其是多形性腺瘤(PMA)和Warthin肿瘤(WT),由于其治疗的可变性和PMA的恶性潜能,需要在术前准确区分。传统成像虽然有价值,但精度有限。本研究采用多层计算机断层扫描(MSCT)放射组学结合血清α - l -聚焦酶(AFU)水平来开发一种诊断模型,旨在提高临床识别和精确治疗。方法:91名患者被随机分配到两个队列中的一个:训练或验证,比例为7:3(64对27)。从收集的MSCT图像中勾画每个肿瘤的感兴趣区域(ROI)以提取放射组学特征。在训练队列中,采用最小绝对收缩和选择算子(LASSO)回归和5倍交叉验证对提取的特征进行筛选并计算Rad-score。通过对rad评分和临床因素进行单因素和多因素logistic回归分析,建立4种诊断模型。然后在验证队列中通过比较受试者工作特征曲线(ROC)和校准曲线来评价4种模型的性能,以选择最佳模型。最后通过nomogram和decision curve analysis (DCA)曲线评价最佳模型的临床应用价值。结果:多因素logistic回归分析显示,血清AFU、rad评分和性别是PMA和WT区分的独立诊断因素。三因素组合的拟形图在训练组和验证组的曲线下面积(AUC)分别为0.934[95%可信区间(CI) 0.863 ~ 1.000]和0.987 (95% CI: 0.956 ~ 1.000),具有很好的拟合优度和临床价值。结论:优化后的nomogram结合MSCT放射组学和AFU提高了PMA与WT区分的准确性,提示其具有开发新的生物标志物的潜力。
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引用次数: 0
Prediction values of different lymph nodes staging systems for survival of children with Wilms tumor. 不同淋巴结分期系统对儿童肾母细胞瘤生存的预测价值。
IF 1.5 4区 医学 Q4 ONCOLOGY Pub Date : 2024-12-31 Epub Date: 2024-12-26 DOI: 10.21037/tcr-24-959
Songqiang Chen, Zhisheng Wan, Shaohua Hu, Weizhen Bu, Yiqun Lu, Zhenli Zhao

Background: Wilms tumor is one of the most common pediatric kidney cancers with poor prognosis. This study aims to explore the predictive values of lymph nodes (LNs), positive lymph node density (LND) and log odds of positive lymph nodes (LODDS) for the 5-year mortality of children with Wilms tumor.

Methods: The cohort study collected the data of 874 participants with Wilms tumor in the Surveillance, Epidemiology, and End Results (SEER) database. The univariate COX proportional risk model was used to explore the possible covariates. The univariate and multivariable COX proportional risk model were employed for exploring the correlations of LNs, LND, and LODDS with the 5-year mortality of Wilms tumor patients. The predictive values of LNs, LND, and LODDS for the 5-year mortality of children with Wilms tumor were evaluated via concordance and 95% confidence interval (CI).

Results: The follow-up time was 5 years, and 804 participants survived in the end. The results delineated that LND >0 [hazard ratio (HR) =1.92, 95% CI: 1.01-3.67] as well as LND ≥0.93 (HR =4.87, 95% CI: 2.42-9.81) were correlated with increased risk of 5-year mortality while LODDS ≥-0.34 (HR =4.09, 95% CI: 2.18-7.65) was linked with elevated risk of 5-year mortality. The concordance of LNs for predicting the 5-year mortality of Wilms tumor patients was 0.623 (95% CI: 0.566-0.681). The concordances of LND, and LODDS for predicting the 5-year mortality of Wilms tumor patients were 0.623 (95% CI: 0.566-0.681) and 0.616 (95% CI: 0.562-0.669).

Conclusions: The predictive value of LODDS for the 5-year mortality of children with Wilms tumor was similar with LNs and LND. The findings might provide a new tool for helping the clinicians identify those with poor prognosis, and timely treatments should be offered to these patients.

背景:肾母细胞瘤是最常见的儿童肾癌之一,预后较差。本研究旨在探讨淋巴结(LNs)、阳性淋巴结密度(LND)和阳性淋巴结对数赔率(LODDS)对儿童Wilms肿瘤5年死亡率的预测价值。方法:队列研究从监测、流行病学和最终结果(SEER)数据库中收集了874名Wilms肿瘤患者的数据。采用单因素COX比例风险模型探讨可能的协变量。采用单因素和多因素COX比例风险模型探讨ln、LND、LODDS与Wilms肿瘤患者5年死亡率的相关性。通过一致性和95%置信区间(CI)评估LNs、LND和LODDS对Wilms肿瘤儿童5年死亡率的预测价值。结果:随访5年,804例患者最终存活。结果显示,LND >[危险比(HR) =1.92, 95% CI: 1.01-3.67]和LND≥0.93 (HR =4.87, 95% CI: 2.42-9.81)与5年死亡率风险升高相关,而LODDS≥-0.34 (HR =4.09, 95% CI: 2.18-7.65)与5年死亡率风险升高相关。预测Wilms肿瘤患者5年死亡率的LNs一致性为0.623 (95% CI: 0.566-0.681)。LND和LODDS预测Wilms肿瘤患者5年死亡率的一致性分别为0.623 (95% CI: 0.566-0.681)和0.616 (95% CI: 0.562-0.669)。结论:LODDS对Wilms肿瘤患儿5年死亡率的预测价值与LNs和LND相似。研究结果可能为临床医生鉴别预后不良的患者提供新的工具,并为这些患者提供及时的治疗。
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引用次数: 0
Construction of a cuproptosis-tricarboxylic acid cycle-associated lncRNA model to predict the prognosis of non-small cell lung cancer. 构建铜绿-三羧酸循环相关lncRNA模型预测非小细胞肺癌预后
IF 1.5 4区 医学 Q4 ONCOLOGY Pub Date : 2024-12-31 Epub Date: 2024-12-27 DOI: 10.21037/tcr-24-660
Xiang Li, Yunlong Zhao, Shengjie Wei, Yuqing Dai, Chun Yi

Background: In cuproptosis, excess copper ions induce cell death via fatty acylation in the tricarboxylic acid (TCA) cycle. However, the effects of cuproptosis-TCA-related long non-coding RNAs (lncRNAs) on the clinical prognosis of non-small cell lung cancer (NSCLC) and the associated tumor microenvironment remain unclear. The purpose of this study is to use cuproptosis-TCA related lncRNAs to predict the prognosis of NSCLC.

Methods: Molecular signature databases and cuproptosis-related publications were made use of identifying cuproptosis-TCA-related genes. They were identified based on Pearson correlation analysis. The prognostic features associated with these lncRNAs were evaluated using the absolute contraction and selection operator and a receiver operating characteristic curve analysis. Additionally, downstream functional enrichment and immunoinfiltration were analyzed to examine the immunotherapeutic responses of patients with NSCLC.

Results: Eleven cuproptosis-TCA-associated lncRNAs were identified. A high-risk group was compared with a low-risk group based on risk scores, and the high-risk group had a significantly lower overall survival (OS). We established a prognostic risk profile, and based on these characteristics and clinical staging, a nomogram was constructed. An analysis of functional enrichment revealed the involvement of pathways associated with cellular and humoral immunity and fatty acylation. Risk scores differed significantly based on immune cells and pathways (antigen-presenting cell co-stimulation). Moreover, TP53, TTN, and MUC16 mutation status were strongly associated with risk scores, with patients identified as having a higher risk of NSCLC being more responsive to immunotherapy.

Conclusions: Eleven cuproptosis-TCA-associated lncRNAs can be used to predict the prognosis of NSCLC patients, thereby providing a new theoretical basis for immunotherapy.

背景:在铜中毒中,过量的铜离子通过三羧酸(TCA)循环中的脂肪酰化诱导细胞死亡。然而,cuprotositca相关长链非编码rna (lncRNAs)对非小细胞肺癌(NSCLC)临床预后及相关肿瘤微环境的影响尚不清楚。本研究旨在利用cuprotosis - tca相关lncrna预测NSCLC的预后。方法:利用分子特征数据库和铜腐病相关文献,鉴定铜腐病- tca相关基因。根据Pearson相关分析对其进行识别。与这些lncrna相关的预后特征使用绝对收缩和选择算子和接受者工作特征曲线分析进行评估。此外,通过分析下游功能富集和免疫浸润来检测非小细胞肺癌患者的免疫治疗反应。结果:共鉴定出11个cuprotosis - tca相关的lncrna。根据风险评分将高风险组与低风险组进行比较,高风险组的总生存期(OS)明显较低。我们建立了预后风险概况,并基于这些特征和临床分期,构建了nomogram。功能富集分析揭示了与细胞和体液免疫以及脂肪酰化相关的途径的参与。根据免疫细胞和途径(抗原提呈细胞共刺激),风险评分有显著差异。此外,TP53、TTN和MUC16突变状态与风险评分密切相关,被确定为NSCLC风险较高的患者对免疫治疗更有反应。结论:11个cuprotosis - tca相关lncrna可用于预测NSCLC患者的预后,从而为免疫治疗提供新的理论依据。
{"title":"Construction of a cuproptosis-tricarboxylic acid cycle-associated lncRNA model to predict the prognosis of non-small cell lung cancer.","authors":"Xiang Li, Yunlong Zhao, Shengjie Wei, Yuqing Dai, Chun Yi","doi":"10.21037/tcr-24-660","DOIUrl":"https://doi.org/10.21037/tcr-24-660","url":null,"abstract":"<p><strong>Background: </strong>In cuproptosis, excess copper ions induce cell death via fatty acylation in the tricarboxylic acid (TCA) cycle. However, the effects of cuproptosis-TCA-related long non-coding RNAs (lncRNAs) on the clinical prognosis of non-small cell lung cancer (NSCLC) and the associated tumor microenvironment remain unclear. The purpose of this study is to use cuproptosis-TCA related lncRNAs to predict the prognosis of NSCLC.</p><p><strong>Methods: </strong>Molecular signature databases and cuproptosis-related publications were made use of identifying cuproptosis-TCA-related genes. They were identified based on Pearson correlation analysis. The prognostic features associated with these lncRNAs were evaluated using the absolute contraction and selection operator and a receiver operating characteristic curve analysis. Additionally, downstream functional enrichment and immunoinfiltration were analyzed to examine the immunotherapeutic responses of patients with NSCLC.</p><p><strong>Results: </strong>Eleven cuproptosis-TCA-associated lncRNAs were identified. A high-risk group was compared with a low-risk group based on risk scores, and the high-risk group had a significantly lower overall survival (OS). We established a prognostic risk profile, and based on these characteristics and clinical staging, a nomogram was constructed. An analysis of functional enrichment revealed the involvement of pathways associated with cellular and humoral immunity and fatty acylation. Risk scores differed significantly based on immune cells and pathways (antigen-presenting cell co-stimulation). Moreover, TP53, TTN, and MUC16 mutation status were strongly associated with risk scores, with patients identified as having a higher risk of NSCLC being more responsive to immunotherapy.</p><p><strong>Conclusions: </strong>Eleven cuproptosis-TCA-associated lncRNAs can be used to predict the prognosis of NSCLC patients, thereby providing a new theoretical basis for immunotherapy.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 12","pages":"6807-6824"},"PeriodicalIF":1.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genomic landscape of medulloblastoma subtypes in an Asian cohort. 亚洲队列中成神经管细胞瘤亚型的基因组景观。
IF 1.5 4区 医学 Q4 ONCOLOGY Pub Date : 2024-12-31 Epub Date: 2024-12-18 DOI: 10.21037/tcr-24-1350
Dongming Han, Xin Jin, Jiankang Li

Background: Medulloblastoma (MB) is a highly malignant childhood brain tumor. Previous research on the genetic underpinnings of MB subtypes has predominantly focused on European and American cohorts. Given the notable genetic differences between Asian and other populations, a subtype-specific study on an Asian cohort is essential to provide comprehensive insights into MB within this demographic. The aim of this study is to investigate the genomic landscape of MB subtypes in an Asian cohort to better understand the genetic variations and potential implications for clinical practice.

Methods: We conducted a study on an Asian cohort comprising 113 MB patients. Genomic sequencing was performed using MGISEQ-2000 platform. We analyzed the participants' characteristics and compared them with previous studies. All germline variants of the ten susceptibility genes of interest (APC, BRCA2, PTCH1, PTCH2, ELP1, SUFU, CTNNB1, SMARCA4, GPR161, and TP53) were annotated and validated.

Results: Our study identified 14 valid germline variants that met our criteria, with these variants being detected in the genes APC, BRCA2, PTCH1, PTCH2, ELP1, and SUFU. Of these, six variants were classified as pathogenic in ClinVar: two in PTCH2 (c.C1573T), one in ELP1 (c.C583T), and three in PTCH1 (c.G1370T, c.C2066T, c.C529T). The remaining eight variants were of uncertain significance, including those in SUFU (c.T833C), ELP1 (c.T2A), BRCA2 (c.G7488C), and APC (c.C3247A, c.A1G, c.A8042G, c.A3056G, c.G822C). Our findings highlight a subtype-based germline variant landscape specific to the Asian cohort and reinforce the connection between SUFU, PTCH1, and the SHH subtype of MB. Additionally, the identification of ELP1-related cases supports the newest findings in this area and provides typical copy number variation (CNV) results for future investigation.

Conclusions: This study provides valuable insights into the genetic landscape of MB in an Asian cohort, emphasizing the importance of population-specific research. The subtype-specific germline variant landscape identified in this study contributes to the understanding of MB and its genetic underpinnings in Asian populations, potentially guiding future research and therapeutic strategies.

背景:髓母细胞瘤是一种高度恶性的儿童脑肿瘤。先前对MB亚型遗传基础的研究主要集中在欧洲和美国的队列中。鉴于亚洲人和其他人群之间存在显著的遗传差异,对亚洲人群进行亚型特异性研究对于全面了解该人群中的MB至关重要。本研究的目的是研究亚洲队列中MB亚型的基因组景观,以更好地了解遗传变异及其对临床实践的潜在影响。方法:我们对113名MB患者进行了一项亚洲队列研究。使用MGISEQ-2000平台进行基因组测序。我们分析了参与者的特征,并与之前的研究进行了比较。对10个感兴趣的易感基因(APC、BRCA2、PTCH1、PTCH2、ELP1、SUFU、CTNNB1、SMARCA4、GPR161和TP53)的所有种系变异进行了注释和验证。结果:我们的研究确定了14个符合我们标准的有效种系变异,这些变异在APC、BRCA2、PTCH1、PTCH2、ELP1和SUFU基因中被检测到。其中,6个变异在ClinVar中被分类为致病性:2个在PTCH2中(c.C1573T), 1个在ELP1中(c.C583T), 3个在PTCH1中(c.G1370T, c.C2066T, c.C529T)。其余8个变异的意义不确定,包括SUFU (c.T833C)、ELP1 (c.T2A)、BRCA2 (c.G7488C)和APC (c.C3247A、c.A1G、c.A8042G、c.A3056G、c.G822C)。我们的研究结果强调了亚洲人群特有的基于亚型的种系变异景观,并加强了SUFU、PTCH1和MB的SHH亚型之间的联系。此外,elp1相关病例的鉴定支持了该领域的最新发现,并为未来的研究提供了典型的拷贝数变异(CNV)结果。结论:本研究为亚洲队列中MB的遗传景观提供了有价值的见解,强调了人群特异性研究的重要性。本研究确定的亚型特异性种系变异景观有助于了解MB及其在亚洲人群中的遗传基础,可能指导未来的研究和治疗策略。
{"title":"Genomic landscape of medulloblastoma subtypes in an Asian cohort.","authors":"Dongming Han, Xin Jin, Jiankang Li","doi":"10.21037/tcr-24-1350","DOIUrl":"https://doi.org/10.21037/tcr-24-1350","url":null,"abstract":"<p><strong>Background: </strong>Medulloblastoma (MB) is a highly malignant childhood brain tumor. Previous research on the genetic underpinnings of MB subtypes has predominantly focused on European and American cohorts. Given the notable genetic differences between Asian and other populations, a subtype-specific study on an Asian cohort is essential to provide comprehensive insights into MB within this demographic. The aim of this study is to investigate the genomic landscape of MB subtypes in an Asian cohort to better understand the genetic variations and potential implications for clinical practice.</p><p><strong>Methods: </strong>We conducted a study on an Asian cohort comprising 113 MB patients. Genomic sequencing was performed using MGISEQ-2000 platform. We analyzed the participants' characteristics and compared them with previous studies. All germline variants of the ten susceptibility genes of interest (<i>APC, BRCA2, PTCH1, PTCH2, ELP1, SUFU, CTNNB1, SMARCA4, GPR161</i>, and <i>TP53</i>) were annotated and validated.</p><p><strong>Results: </strong>Our study identified 14 valid germline variants that met our criteria, with these variants being detected in the genes <i>APC, BRCA2, PTCH1, PTCH2, ELP1</i>, and <i>SUFU</i>. Of these, six variants were classified as pathogenic in ClinVar: two in <i>PTCH2</i> (c.C1573T), one in <i>ELP1</i> (c.C583T), and three in <i>PTCH1</i> (c.G1370T, c.C2066T, c.C529T). The remaining eight variants were of uncertain significance, including those in <i>SUFU</i> (c.T833C), <i>ELP1</i> (c.T2A), <i>BRCA2</i> (c.G7488C), and <i>APC</i> (c.C3247A, c.A1G, c.A8042G, c.A3056G, c.G822C). Our findings highlight a subtype-based germline variant landscape specific to the Asian cohort and reinforce the connection between <i>SUFU</i>, <i>PTCH1</i>, and the SHH subtype of MB. Additionally, the identification of ELP1-related cases supports the newest findings in this area and provides typical copy number variation (CNV) results for future investigation.</p><p><strong>Conclusions: </strong>This study provides valuable insights into the genetic landscape of MB in an Asian cohort, emphasizing the importance of population-specific research. The subtype-specific germline variant landscape identified in this study contributes to the understanding of MB and its genetic underpinnings in Asian populations, potentially guiding future research and therapeutic strategies.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 12","pages":"6721-6731"},"PeriodicalIF":1.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Treatment of immune checkpoint inhibitor-related colitis: a narrative review. 免疫检查点抑制剂相关结肠炎的治疗:叙述性回顾
IF 1.5 4区 医学 Q4 ONCOLOGY Pub Date : 2024-12-31 Epub Date: 2024-12-27 DOI: 10.21037/tcr-24-2150
Shiyang Wang, Hanping Wang

Background and objective: Cancer is one of the most difficult diseases facing modern medicine, and increasing amounts of research and clinical treatments are being applied to the treatment of cancer. Immunotherapy, particularly immune checkpoint inhibitor (ICI) therapy, has revolutionized the treatment and overall survival of patients with several different types of cancer. Approximately one-third of patients treated with ICIs may experience immune-related adverse events (irAEs). Immune checkpoint inhibitor-associated colitis (ICIC) is the most common irAE with an incidence of approximately 8-10%, ICIC usually presents as watery or bloody diarrhea, and if the symptoms are severe, ICI treatment must be interrupted or even terminated. This review summarizes the epidemiology, pathogenesis, clinical characteristics, and therapies of ICIC, focusing on the use of biologics, in order to propose treatment options in different situations to control immune checkpoint inhibitor-related colitis as soon as possible.

Methods: To find relevant articles for this narrative review paper, a combination of keywords such as immune checkpoint inhibitor-related colitis, corticosteroids, biologics were searched for in PubMed databases.

Key content and findings: The pathogenesis of ICIC is complex and primarily involves antitumor effects and indirect damage to colonic tissues, as well as the activation of specific proinflammatory pathways. Corticosteroids (CSs) are the first line of treatment for ICIC, but steroid-refractory or steroid-resistant cases often occur. Patients with irAE colitis respond favorably to biologics, and patients with CS-resistant/refractory enterocolitis can benefit from the early use of biologics.

Conclusions: Biologics are currently recommended for the treatment of ICIC but are usually used as a supplement after the failure of first-line CS therapy. Patients with irAE colitis respond favorably to biologics, and patients with CS-resistant/refractory enterocolitis can benefit from the early use of biologics. Biologics (alone or in combination with CS) should be considered as an early therapy option for high-risk patients rather than just an escalation after a failure to respond to CS.

背景与目的:癌症是现代医学面临的最困难的疾病之一,越来越多的研究和临床治疗正在应用于癌症的治疗。免疫疗法,特别是免疫检查点抑制剂(ICI)疗法,已经彻底改变了几种不同类型癌症患者的治疗和总体生存率。大约三分之一接受ICIs治疗的患者可能经历免疫相关不良事件(irAEs)。免疫检查点抑制剂相关性结肠炎(ICIC)是最常见的irAE,发病率约为8-10%,ICIC通常表现为水样或带血腹泻,如果症状严重,必须中断甚至终止ICI治疗。本文综述了ICIC的流行病学、发病机制、临床特点和治疗方法,重点介绍了生物制剂的应用,以期在不同情况下提出治疗方案,尽快控制免疫检查点抑制剂相关性结肠炎。方法:结合免疫检查点抑制剂相关性结肠炎、皮质类固醇、生物制剂等关键词,在PubMed数据库中检索相关文献。关键内容和发现:ICIC的发病机制复杂,主要涉及抗肿瘤作用和对结肠组织的间接损伤,以及特异性促炎途径的激活。皮质类固醇(CSs)是ICIC的一线治疗方法,但经常发生类固醇难治性或类固醇抵抗性病例。irAE型结肠炎患者对生物制剂反应良好,cs耐药/难治性小肠结肠炎患者可从早期使用生物制剂中获益。结论:生物制剂目前被推荐用于治疗ICIC,但通常作为一线CS治疗失败后的补充。irAE型结肠炎患者对生物制剂反应良好,cs耐药/难治性小肠结肠炎患者可从早期使用生物制剂中获益。生物制剂(单独使用或与CS联合使用)应被视为高危患者的早期治疗选择,而不仅仅是CS无效后的升级治疗。
{"title":"Treatment of immune checkpoint inhibitor-related colitis: a narrative review.","authors":"Shiyang Wang, Hanping Wang","doi":"10.21037/tcr-24-2150","DOIUrl":"https://doi.org/10.21037/tcr-24-2150","url":null,"abstract":"<p><strong>Background and objective: </strong>Cancer is one of the most difficult diseases facing modern medicine, and increasing amounts of research and clinical treatments are being applied to the treatment of cancer. Immunotherapy, particularly immune checkpoint inhibitor (ICI) therapy, has revolutionized the treatment and overall survival of patients with several different types of cancer. Approximately one-third of patients treated with ICIs may experience immune-related adverse events (irAEs). Immune checkpoint inhibitor-associated colitis (ICIC) is the most common irAE with an incidence of approximately 8-10%, ICIC usually presents as watery or bloody diarrhea, and if the symptoms are severe, ICI treatment must be interrupted or even terminated. This review summarizes the epidemiology, pathogenesis, clinical characteristics, and therapies of ICIC, focusing on the use of biologics, in order to propose treatment options in different situations to control immune checkpoint inhibitor-related colitis as soon as possible.</p><p><strong>Methods: </strong>To find relevant articles for this narrative review paper, a combination of keywords such as immune checkpoint inhibitor-related colitis, corticosteroids, biologics were searched for in PubMed databases.</p><p><strong>Key content and findings: </strong>The pathogenesis of ICIC is complex and primarily involves antitumor effects and indirect damage to colonic tissues, as well as the activation of specific proinflammatory pathways. Corticosteroids (CSs) are the first line of treatment for ICIC, but steroid-refractory or steroid-resistant cases often occur. Patients with irAE colitis respond favorably to biologics, and patients with CS-resistant/refractory enterocolitis can benefit from the early use of biologics.</p><p><strong>Conclusions: </strong>Biologics are currently recommended for the treatment of ICIC but are usually used as a supplement after the failure of first-line CS therapy. Patients with irAE colitis respond favorably to biologics, and patients with CS-resistant/refractory enterocolitis can benefit from the early use of biologics. Biologics (alone or in combination with CS) should be considered as an early therapy option for high-risk patients rather than just an escalation after a failure to respond to CS.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 12","pages":"7002-7014"},"PeriodicalIF":1.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Translational cancer research
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