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An anoikis-related gene signature predicts prognosis in patients with acute myeloid leukemia and immunotherapy. 嗜酸相关基因标记预测急性髓性白血病和免疫治疗患者的预后。
IF 3.6 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-15 eCollection Date: 2024-01-01 DOI: 10.62347/MJTA2660
Rong Xu, Ashuai Du, Jianbo Li, Qinglong Yang

Acute myeloid leukemia (AML) is a malignant blood disorder and the most common type of acute leukemia in adults. Notwithstanding the plethora of therapeutic modalities, a significant cohort of patients fail to respond to treatment and experience relapse. Anoikis, a distinct modality of programmed cell death, has been linked to cancer progression. However, the prognostic significance of anoikis in AML remains unclear. In this study, a non-negative matrix factorization algorithm was utilized to efficiently reduce the dimensions of merged datasets. We used differential analysis, weighted gene co-expression network analysis (WGCNA), univariate Cox regression, and least absolute shrinkage and selection operator (LASSO) regression to identify genes associated with prognosis and develop a risk scoring model. Immunohistochemistry was conducted to assess the expression levels of key genes in clinical samples. The association between risk score and the tumor microenvironment (TME), stemness, clinical characteristics, and immunotherapy was evaluated. We identified 41 AML anoikis-related genes (ANRGs) related to survival, and seven genes were chosen to develop prognostic models. The prognostic risk score combined with the clinical and pathological features of AML was used to develop a nomogram, and decision curve analysis demonstrated the net clinical benefit of the model. Furthermore, analysis of ANRGs revealed that PDGFRB inhibition significantly reduced the proliferation of AML cells, promoted apoptosis, and inhibited AML progression both in vitro and in vivo, indicating that PDGFRB plays a crucial role in AML development.

急性髓性白血病(AML)是一种恶性血液疾病,是成人中最常见的急性白血病类型。尽管有过多的治疗方式,显著队列的患者未能响应治疗和经历复发。Anoikis是一种独特的程序性细胞死亡模式,与癌症进展有关。然而,anoikis在AML中的预后意义尚不清楚。本研究采用非负矩阵分解算法对合并数据集进行有效降维。我们使用差异分析、加权基因共表达网络分析(WGCNA)、单变量Cox回归和最小绝对收缩和选择算子(LASSO)回归来识别与预后相关的基因,并建立风险评分模型。免疫组化检测临床样品中关键基因的表达水平。评估风险评分与肿瘤微环境(TME)、干性、临床特征和免疫治疗之间的关系。我们确定了41个与生存相关的AML不良相关基因(ANRGs),并选择了7个基因来建立预后模型。预后风险评分结合AML的临床和病理特征形成nomogram,决策曲线分析显示了该模型的净临床效益。此外,ANRGs分析显示,PDGFRB抑制在体外和体内均显著降低AML细胞增殖,促进细胞凋亡,抑制AML进展,表明PDGFRB在AML发展中起着至关重要的作用。
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引用次数: 0
The small protein LINC01547-ORF inhibits colorectal cancer progression by regulating the CLDN18-FAK-AKT axis. 小蛋白LINC01547-ORF通过调节CLDN18-FAK-AKT轴抑制结直肠癌的进展。
IF 3.6 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-15 eCollection Date: 2024-01-01 DOI: 10.62347/PNKH7683
Shuai Zhang, Siguang Xu, Dandan Li, Songxin Wu, Miaomiao Han, Yifei Han, Zixi Wang, Dan Qiao, Hang Yuan, Baoshun Du, Hongwei Chen, Zheying Zhang

Long non-coding RNA (lncRNA)-encoded small proteins play a major role in colorectal cancer. To identify more functional encoded small proteins, ribosome profiling data from colorectal cancer (CRC) cells were screened for ribosome-associated lncRNAs. The search identified LINC01547 that was shown to encode a small protein of 76 amino acids, termed LINC01547-ORF. Real-time quantitative fluorescence showed that LINC01547 expression was downregulated in colorectal cancer tissues. However, cell functional assays revealed that LINC01547 inhibited the proliferation and migration of colorectal cancer cell lines. Meanwhile, western blot and immunofluorescence assays confirmed that LINC01547 encoded LINC01547-ORF. Cellular functional assays indicated that compared with LINC01547 itself, LINC01547-ORF inhibited the proliferation and migration of colorectal cancer cell lines. Gene set enrichment analysis identified enrichment in the focal adhesion pathway and association with CLDN18 protein, whereas protein molecular docking models revealed interacting domains and amino acid residue sites. Of note, co-immunoprecipitation and immunofluorescence experiments showed that LINC01547-ORF could bind to the CLDN18 protein and that this interaction reduced CLDN18 ubiquitination, thereby promoting protein expression. Finally, western blot and immunofluorescence assays confirmed that LINC01547-ORF could target CLDN18 to inhibit the FAK/PI3K/AKT signaling pathway, suppressing colorectal cancer cell development. These findings suggest that the LINC01547-ORF-encoded small protein inhibits proliferation and migration in colorectal cancer, thereby offering a promising direction for treating this disease.

长链非编码RNA (lncRNA)编码的小蛋白在结直肠癌中发挥重要作用。为了鉴定更多功能编码的小蛋白,对结直肠癌(CRC)细胞的核糖体分析数据进行了核糖体相关lncrna筛选。研究发现,LINC01547编码一个由76个氨基酸组成的小蛋白,命名为LINC01547- orf。实时荧光定量显示,LINC01547在结直肠癌组织中表达下调。然而,细胞功能实验显示,LINC01547抑制结直肠癌细胞系的增殖和迁移。同时,western blot和免疫荧光检测证实LINC01547编码了LINC01547- orf。细胞功能实验表明,与LINC01547本身相比,LINC01547- orf抑制结直肠癌细胞系的增殖和迁移。基因集富集分析确定了在黏附途径中富集并与CLDN18蛋白相关,而蛋白分子对接模型则揭示了相互作用域和氨基酸残基位点。值得注意的是,免疫共沉淀和免疫荧光实验表明,LINC01547-ORF可以与CLDN18蛋白结合,这种相互作用降低了CLDN18的泛素化,从而促进了蛋白的表达。最后,western blot和免疫荧光实验证实,LINC01547-ORF可以靶向CLDN18,抑制FAK/PI3K/AKT信号通路,抑制结直肠癌细胞的发展。这些发现表明,linc01547 - orf编码的小蛋白抑制结直肠癌的增殖和迁移,从而为治疗结直肠癌提供了一个有希望的方向。
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引用次数: 0
Updated outcomes and exploratory analysis of RENMIN-215: tislelizumab plus fruquintinib and fecal microbiota transplantation in refractory microsatellite stable metastatic colorectal cancer. 人民币-215:替利单抗联合fruquintinib和粪便微生物群移植治疗难治性微卫星稳定转移性结直肠癌的最新结果和探索性分析。
IF 3.6 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-15 eCollection Date: 2024-01-01 DOI: 10.62347/XKUJ3012
Wensi Zhao, Yuan Chen, Jiping Xiao, Ze Tang, Li Wang, Yiping Ren, Yongshun Chen

Primary analysis of the open-label, single-arm, phase II RENMIN-215 trial (primary data cutoff date: July 10, 2023) showed promising efficacy and tolerable safety with tislelizumab plus fruquintinib and fecal microbiota transplantation (FMT) in patients with refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Here, we reported updated survival and safety results with a median follow-up of 34.0 months (data cut-off May 20, 2024), as well as patient-reported outcomes and laboratory analysis. Twenty patients with MSS mCRC resistant or refractory to at least second-line therapy were enrolled and received tislelizumab plus fruquintinib and FMT. The primary endpoint was progression-free survival. Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate, safety, health-related quality of life questionnaire and exploratory laboratory tests. In addition, 94 mCRC patients who received third-line or above immunotherapy in real world were screened for propensity score matching (PSM) analysis to compare efficacy. Our results showed that the median OS was 13.7 months (95% CI, 9.3-17.7), and the ORR was 20.0% (95% CI, 5.7-43.7). After PSM, the median OS benefit of the study regimen remained statistically significant (HR = 0.26; 95% CI, 0.07-0.95; P = 0.042). Patients with primary tumor surgery had better clinical outcomes. No new safety concerns were detected. Seven (35.0%) patients had one or more grade 3 treatment-related adverse events. The majority of patients had improved or stable global health status (GHS). Median time to deterioration for GHS was 7.7 months. Peripheral blood lymphocyte analysis showed that increased gamma-delta 2 T cells were positively associated with improved response and survival. To conclude, the updated results provide further evidence of sustained antitumor activity of tislelizumab plus fruquintinib and FMT in heavily pretreated MSS mCRC patients with a consistent safety profile.

开放标签、单臂、II期研究(主要数据截止日期:2023年7月10日)的初步分析显示,tislelizumab联合fruquintinib和粪便微生物群移植(FMT)治疗难治性微卫星稳定(MSS)转移性结直肠癌(mCRC)患者有希望的疗效和可耐受的安全性。在这里,我们报告了中位随访34.0个月(数据截止日期为2024年5月20日)的最新生存和安全性结果,以及患者报告的结果和实验室分析。20例至少对二线治疗耐药或难治的MSS mCRC患者入组,并接受tislelizumab + fruquintinib和FMT治疗。主要终点为无进展生存期。次要终点包括总生存期(OS)、客观缓解率(ORR)、疾病控制率、安全性、健康相关生活质量问卷调查和探索性实验室检查。此外,94名在现实世界中接受三线或以上免疫治疗的mCRC患者进行倾向评分匹配(PSM)分析以比较疗效。我们的结果显示中位OS为13.7个月(95% CI, 9.3-17.7), ORR为20.0% (95% CI, 5.7-43.7)。PSM后,研究方案的中位OS获益仍然具有统计学意义(HR = 0.26;95% ci, 0.07-0.95;P = 0.042)。原发肿瘤手术患者临床效果较好。没有发现新的安全隐患。7例(35.0%)患者有一个或多个3级治疗相关不良事件。大多数患者的总体健康状况(GHS)改善或稳定。到GHS恶化的中位时间为7.7个月。外周血淋巴细胞分析显示,增加的γ - δ 2 T细胞与改善的反应和生存呈正相关。总之,最新的结果进一步证明,tislelizumab联合fruquintinib和FMT在重度预处理的MSS mCRC患者中具有持续的抗肿瘤活性,并且具有一致的安全性。
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引用次数: 0
Machine learning models using multiparametric MRI for preoperative risk stratification in endometrial cancer. 使用多参数MRI进行子宫内膜癌术前风险分层的机器学习模型。
IF 3.6 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-15 eCollection Date: 2024-01-01 DOI: 10.62347/MALY3908
Vu Pham Thao Vy, Jerry Chin-Wei Chien, Wiwan Irama, Hao-Yang Wu, Tzu-I Wu, Wei-Yu Chen, Chia-Hao Liang, Truong Nguyen Khanh Hung, Wilson T Lao, Wing P Chan

This study evaluated the efficacy of machine learning and radiomics of preoperative multiparameter MRIs in predicting low- vs high-risk histopathologic features and early vs advanced FIGO stage (IA vs IB or higher) in endometrial cancer. This retrospective study of patients with endometrial cancer histologically confirmed from 2008 through 2023 excluded those with: (a) previous treatment for endometrial carcinoma, (b) incomplete MRI examinations or low-quality MR images, (c) incomplete pathology reports, (d) non-visualized tumors on MRI, or (e) distant metastases. In total, 110 radiomic features were extracted using commercial PACS built-in software following segmentation after sagittal T2-weighted imaging (T2WI), contrast enhanced T1-weighted imaging (CE-T1WI), and diffusion weighted imaging (DWI). The radiomic features from each imaging sequence were utilized for initial modeling. A combined model, which included features retained from all 3 sequences, was then established. The area under the receiver operating characteristic curve (AUC) determined the efficacy of each model. For 5 specific histopathologic features, the combined model achieved AUCs of 0.87 (95% CI, 0.85-0.90), 0.90 (95% CI, 0.88-0.92), 0.88 (95% CI, 0.87-0.90), 0.88 (95% CI, 0.86-0.92), and 0.87 (95% CI, 0.86-0.90). This model incorporated 38 radiomic features: 12 from T2WI, 17 from CE-T1WI, and 9 from DWI. In conclusion, an MRI radiomics-based model can differentiate between early- and advanced-stage endometrial cancer and between low- and high-risk histologic markers, giving it the potential to predict high risk and stratify preoperative risk in those with endometrial cancer. The findings may aid personalized preoperative assessments to guide clinical decision-making in endometrial cancer.

本研究评估了机器学习和术前多参数mri放射组学在预测子宫内膜癌低/高风险组织病理特征和早期/晚期FIGO分期(IA / IB或更高)的有效性。本回顾性研究对2008年至2023年组织学证实的子宫内膜癌患者进行了研究,排除了以下患者:(a)既往子宫内膜癌治疗,(b) MRI检查不完整或MRI图像质量低,(c)病理报告不完整,(d) MRI未显示肿瘤,或(e)远处转移。在矢状面t2加权成像(T2WI)、对比度增强t1加权成像(CE-T1WI)和弥散加权成像(DWI)后,使用商用PACS内置软件进行分割,共提取110个放射学特征。利用每个成像序列的放射学特征进行初始建模。然后建立了包含所有3个序列保留的特征的组合模型。受试者工作特征曲线下面积(AUC)决定了各模型的疗效。对于5个特定的组织病理特征,联合模型的auc分别为0.87 (95% CI, 0.85-0.90)、0.90 (95% CI, 0.88-0.92)、0.88 (95% CI, 0.87-0.90)、0.88 (95% CI, 0.86-0.92)和0.87 (95% CI, 0.86-0.90)。该模型包含38个放射学特征:T2WI 12个,CE-T1WI 17个,DWI 9个。总之,基于MRI放射组学的模型可以区分早期和晚期子宫内膜癌,以及低风险和高风险的组织学标志物,从而有可能预测子宫内膜癌患者的高风险和术前风险分层。研究结果可能有助于个性化术前评估,指导子宫内膜癌的临床决策。
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引用次数: 0
Recurrence risk of erythropoiesis-stimulating agents on early-stage urothelial carcinoma in patients with end stage renal disease. 促红细胞生成剂对终末期肾病患者早期尿路上皮癌复发的影响
IF 3.6 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-15 eCollection Date: 2024-01-01 DOI: 10.62347/UJAT9290
Hui-Ying Liu, Hao Lun Luo, Wen-Chin Lee, Yin Lun Chang, Yen-Ting Wu, Hung Jen Wang, Yao Chi Chuang, Yen Ta Chen, Lung-Chih Li, John L Gore, Chiang-Chi Huang

Urothelial carcinoma (UC) predominantly arises in the bladder, but upper tract urothelial carcinomas (UTUCs) comprise 5-10% of cases. Patients with end-stage renal disease (ESRD) are at increased risk for UC, and erythropoiesis-stimulating agents (ESAs) are frequently used to manage anemia in ESRD. However, ESA use in cancer patients raises concerns about tumor progression and survival outcomes. This study aimed to assess the impact of ESA use on tumor recurrence, cancer-specific survival (CSS), and overall survival (OS) in patients with ESRD and early-stage UC. We analyzed data from the Chang-Gung Research Database (CGRD) in Taiwan, including 850 patients with ESRD and non-muscle-invasive bladder cancer (NMIBC) and 492 patients with ESRD and localized UTUC. The ESA group was compared to a non-ESA cohort, and inverse probability of treatment weighting (IPTW) was applied to minimize selection bias. Kaplan-Meier curves and log-rank tests were used to evaluate bladder recurrence-free survival, CSS, and OS. In NMIBC patients, ESA use did not significantly affect bladder recurrence-free survival, CSS, or OS. Similarly, ESA use in localized UTUC patients did not increase the risk of bladder recurrence or negatively impact CSS and OS. However, UTUC patients treated with ESA demonstrated a significantly increased risk of contralateral recurrence (P < 0.001). The use of ESA in patients with ESRD and early-stage UC appears safe regarding bladder recurrence, CSS, and OS, but clinicians should remain vigilant for contralateral recurrence in localized UTUC. These findings provide valuable insights into the complex management of anemia in patients with concurrent ESRD and UC, emphasizing the need for tailored clinical monitoring in this high-risk population.

尿路上皮癌(UC)主要发生在膀胱,但上尿路尿路上皮癌(UTUCs)占5-10%的病例。终末期肾病(ESRD)患者发生UC的风险增加,促红细胞生成剂(ESAs)常用于ESRD患者的贫血管理。然而,在癌症患者中使用ESA引起了对肿瘤进展和生存结果的担忧。本研究旨在评估ESA使用对ESRD和早期UC患者肿瘤复发、癌症特异性生存(CSS)和总生存(OS)的影响。我们分析了来自台湾Chang-Gung研究数据库(CGRD)的数据,包括850例ESRD合并非肌肉侵袭性膀胱癌(NMIBC)患者和492例ESRD合并局限性UTUC患者。将ESA组与非ESA组进行比较,并应用治疗加权逆概率(IPTW)来最小化选择偏差。Kaplan-Meier曲线和log-rank检验用于评估膀胱无复发生存率、CSS和OS。在NMIBC患者中,使用ESA对膀胱无复发生存、CSS或OS没有显著影响。同样,局部UTUC患者使用ESA不会增加膀胱复发的风险,也不会对CSS和OS产生负面影响。然而,接受ESA治疗的UTUC患者对侧复发的风险显著增加(P < 0.001)。ESRD和早期UC患者在膀胱复发、CSS和OS方面使用ESA是安全的,但临床医生应警惕局部UTUC对侧复发。这些发现为并发ESRD和UC患者贫血的复杂管理提供了有价值的见解,强调了在这一高危人群中定制临床监测的必要性。
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引用次数: 0
Machine learning-based prognostic models and factors influencing the benefit of surgery on primary lesion for patients with lung cancer brain metastases. 基于机器学习的预后模型和影响肺癌脑转移患者原发病变手术获益的因素。
IF 3.6 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-15 eCollection Date: 2024-01-01 DOI: 10.62347/PRFQ9244
Xixi Zhao, Chaofan Li, Mengjie Liu, Zeyao Feng, Xinyu Wei, Yusheng Wang, Jiaqi Zhao, Shuqun Zhang, Jingkun Qu

Brain metastasis is very common in lung cancer and it's a fatal disease with extremely poor prognosis. Until now, there has been a lack of accurate and efficient prognostic models for patients with lung cancer brain metastases (LCBM), and the factors influencing the effectiveness of the surgery on primary lesion for these patients remain unclear. We used 7 machine learning algorithms to create prognostic models to predict the overall survival (OS) of LCBM based on the data from the Surveillance Epidemiology and End Results. Then, a series of validation methods, including area under the curve values, receiver operating characteristic curve analysis, calibration curves, decision curve analysis and external data validation were used to confirm the high discrimination, accuracy, and clinical applicability of the XGBoost models. Propensity score matching adjusted analysis was conducted for further stratified analysis to find factors influencing the benefit of surgery on primary lesion for LCBM. Models using XGBoost algorithm performed best. Surgery on primary lesion was a favorable independent prognostic factor for LCBM. Age > 70 years old, blacks, grade IV, stage T4, N3, other distant organ metastases, squamous cell carcinoma, large cell carcinoma and no radiation were all unfavorable factors of primary lung tumor surgery for the prognosis of LCBM. Our study is the first one to create highly accurate AI models to predict the OS of LCBM. Our in-depth stratified analysis found some influence factors of surgery on primary lesion for the prognosis of LCBM.

脑转移在肺癌中非常常见,是一种预后极差的致命疾病。到目前为止,对于肺癌脑转移(LCBM)患者缺乏准确有效的预后模型,影响这些患者原发病变手术效果的因素也不清楚。我们使用7种机器学习算法创建预后模型,根据监测流行病学和最终结果的数据预测LCBM的总生存期(OS)。然后,通过曲线下面积值、受试者工作特征曲线分析、校准曲线、决策曲线分析和外部数据验证等一系列验证方法,证实了XGBoost模型具有较高的辨别力、准确性和临床适用性。进行倾向评分匹配调整分析,进一步分层分析,寻找影响LCBM原发病变手术获益的因素。使用XGBoost算法的模型表现最好。原发病变的手术是LCBM的一个有利的独立预后因素。年龄bb0 ~ 70岁、黑人、IV级、T4期、N3期、其他远处器官转移、鳞状细胞癌、大细胞癌、无放疗均为原发性肺肿瘤手术对LCBM预后的不利因素。我们的研究是第一个创建高度精确的人工智能模型来预测LCBM的操作系统。我们通过深入的分层分析,发现了手术对原发性病变对LCBM预后的一些影响因素。
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引用次数: 0
Quercetin suppresses cell viability in triple-negative breast cancer by targeting ORM2. 槲皮素通过靶向ORM2抑制三阴性乳腺癌细胞活力。
IF 3.6 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-15 eCollection Date: 2024-01-01 DOI: 10.62347/DEPW1251
Xianhua Liu, Zhijun Chen

Triple-negative breast cancer (TNBC) is known for its aggressive nature, and Quercetin (QUE) has shown potential anti-cancer effects. In this study, we determined the IC50 of QUE for inhibiting cell viability in multiple TNBC, non-TNBC, and normal breast cell lines. We compared the expression of ORM2 in TNBC clinical samples and normal tissues. Additionally, we measured ORM2 expression in TNBC and normal breast cell lines. We determined the IC50 of QUE for inhibiting cell viability after ORM2 knockdown. An orthotopic implantation mice model was used to evaluate the treatment effect of QUE. We also conducted molecular docking and amino acid exchange validation to model the binding of QUE to ORM2. Furthermore, we performed a protein-protein interaction network analysis and GO enrichment analysis of differentially expressed genes associated with ORM2 in TNBC. QUE inhibited the viability of both TNBC and non-TNBC cell lines, but it was specifically associated with worse survival in TNBC patients. We observed higher expression of ORM2 in breast cancer cells compared to normal breast cells. Knockdown of ORM2 reduced the viability of TNBC cells. Treatment with QUE inhibited ORM2 expression and decreased viability in TNBC cells. In the animal model, QUE improved survival and downregulated ORM2 expression in tumors. Enrichment analysis provided insights into the potential functions of ORM2. Conclusion: Our findings indicate that QUE directly inhibits TNBC cell viability through its interaction with ORM2. These results contribute to our understanding of the anti-cancer mechanisms of QUE in TNBC and highlight ORM2 as a potential therapeutic target.

三阴性乳腺癌(TNBC)以其侵袭性而闻名,槲皮素(QUE)已显示出潜在的抗癌作用。在这项研究中,我们测定了QUE在多种TNBC、非TNBC和正常乳腺细胞系中抑制细胞活力的IC50。我们比较了ORM2在TNBC临床样本和正常组织中的表达。此外,我们测量了ORM2在TNBC和正常乳腺细胞系中的表达。我们测定了QUE在ORM2敲除后抑制细胞活力的IC50。采用原位植入小鼠模型评价QUE的治疗效果。我们还进行了分子对接和氨基酸交换验证,以模拟QUE与ORM2的结合。此外,我们对TNBC中与ORM2相关的差异表达基因进行了蛋白相互作用网络分析和氧化石墨烯富集分析。QUE抑制TNBC和非TNBC细胞系的生存能力,但它与TNBC患者的生存率较差特异性相关。我们观察到ORM2在乳腺癌细胞中的表达高于正常乳腺细胞。ORM2的敲低降低了TNBC细胞的活力。QUE抑制ORM2表达,降低TNBC细胞活力。在动物模型中,QUE改善了肿瘤的存活并下调了ORM2的表达。富集分析揭示了ORM2的潜在功能。结论:QUE通过与ORM2的相互作用直接抑制TNBC细胞活力。这些结果有助于我们理解QUE在TNBC中的抗癌机制,并强调ORM2是一个潜在的治疗靶点。
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引用次数: 0
Risk factors of positive lymph node metastasis after radical gastrectomy for gastric cancer and construction of prediction models. 胃癌根治术后淋巴结转移阳性的危险因素及预测模型的建立。
IF 3.6 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-15 eCollection Date: 2024-01-01 DOI: 10.62347/PEDV7297
Gang Dai, Ming-Gan Chen, Deng-Feng Zhu, Yi-Ting Cai, Ming Gao

Positive lymph node metastasis after radical gastrectomy for gastric cancer is a key factor affecting the prognosis of patients, and its mechanism is complex and multifactorial. The aim of this study is to identify the relevant risk factors for positive lymph node metastasis after radical gastrectomy for gastric cancer, and to construct corresponding predictive models. Through a retrospective analysis of clinical data of 316 gastric cancer patients who underwent radical surgery for gastric cancer, we found that age, maximum tumor diameter, degree of tumor differentiation, vascular invasion, depth of tumor infiltration, and CA199 were important factors affecting lymph node metastasis positivity in gastric cancer patients. Based on these factors, we constructed a Nomogram prediction model and found through internal validation that the model has good predictive performance. The area under the receiver operating characteristic curve (AUC) of the training and validation sets were 0.929 and 0.888, respectively. Clinical data of another 390 patients were collected for external verification. External validation results showed that the model had a predictive sensitivity of 75.76% (50/66), a specificity of 91.05% (295/324), and an accuracy of 88.46% (345/390). In addition, we also constructed a neural network prediction model and compared it with the Nomogram model. The results showed that the prediction performance of the Nomogram model was similar to that of the neural network model. The Nomogram model has been validated internally and externally, demonstrating high discrimination and accuracy, providing a convenient, intuitive, and personalized evaluation tool for clinicians, helping to optimize the postoperative management of gastric cancer patients and improve prognosis.

胃癌根治术后淋巴结转移阳性是影响患者预后的关键因素,其机制复杂、多因素。本研究旨在探讨胃癌根治术后淋巴结转移阳性的相关危险因素,并建立相应的预测模型。通过对316例胃癌根治术患者的临床资料进行回顾性分析,我们发现年龄、肿瘤最大直径、肿瘤分化程度、血管浸润程度、肿瘤浸润深度、CA199是影响胃癌患者淋巴结转移阳性的重要因素。基于这些因素,我们构建了Nomogram预测模型,并通过内部验证发现该模型具有良好的预测性能。训练集和验证集的受试者工作特征曲线下面积(AUC)分别为0.929和0.888。另外收集390例患者的临床资料进行外部验证。外部验证结果表明,该模型的预测灵敏度为75.76%(50/66),特异性为91.05%(295/324),准确率为88.46%(345/390)。此外,我们还构建了神经网络预测模型,并与Nomogram模型进行了比较。结果表明,Nomogram模型的预测性能与神经网络模型相当。Nomogram模型得到了内部和外部的验证,具有较高的辨别力和准确性,为临床医生提供了方便、直观、个性化的评估工具,有助于优化胃癌患者的术后管理,改善预后。
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引用次数: 0
ASAP1 promotes extrahepatic cholangiocarcinoma progression by regulating the Wnt/β-catenin pathway in vitro and in vivo. 在体外和体内,ASAP1通过调节Wnt/β-catenin通路促进肝外胆管癌的进展。
IF 3.6 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-15 eCollection Date: 2024-01-01 DOI: 10.62347/RKQX3504
Jiaqi He, Han Liu, Jianhua Cai, Sheng Shen, Jiwen Wang, Houbao Liu

This study sought to identify the relationship between ADP-ribosylation factor GTPase-activating protein (ASAP1) expression and clinical outcomes in extrahepatic cholangiocarcinoma (EHCC) patients. Quantitative real-time PCR (qRT-PCR), Western blotting, and immunohistochemistry were used to analyze the expression of ASAP1 in cholangiocarcinoma (CC) tissue samples and cell lines. The survival rate and clinicopathological characteristics of CC patients were also examined. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to detect cell proliferation. Flow cytometry was used to assess the cell cycle distribution. Both in vitro and in vivo experiments showed that ASAP1 knockdown decreased cell proliferation, inhibited cell cycle progression, and increased apoptosis. ASAP1 regulates Wnt/β-catenin pathway activity in CC, promoting cell migration, and invasion in culture; and promotes tumor development in vivo. ASAP1 plays a key role in EHCC tumor development and could serve as a potential therapeutic target for EHCC.

本研究旨在确定肝外胆管癌(EHCC)患者adp -核糖基化因子gtpase激活蛋白(ASAP1)表达与临床预后之间的关系。采用实时荧光定量PCR (qRT-PCR)、Western blotting和免疫组化技术分析ASAP1在胆管癌(CC)组织样本和细胞系中的表达。同时对CC患者的生存率和临床病理特征进行了分析。细胞计数试剂盒-8 (CCK-8)和5-乙基-2′-脱氧尿苷(EdU)检测细胞增殖。流式细胞术检测细胞周期分布。体外和体内实验均表明,ASAP1敲低可降低细胞增殖,抑制细胞周期进展,增加细胞凋亡。ASAP1调节CC中Wnt/β-catenin通路活性,促进细胞迁移和侵袭;并促进体内肿瘤的发展。ASAP1在EHCC肿瘤发展中起关键作用,可能是EHCC的潜在治疗靶点。
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引用次数: 0
The effect of body mass index at diagnosis on survival of patients with squamous cell head and neck carcinoma. 诊断时体重指数对鳞状细胞头颈部癌患者生存的影响。
IF 3.6 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-15 eCollection Date: 2024-01-01 DOI: 10.62347/UUXK7608
Roberta Pastorino, Denise Pires Marafon, Nicolò Lentini, Ilda Hoxhaj, Adriano Grossi, Luca Giraldi, Antonella Rondinò, Gabriella Cadoni, Jerry Polesel, Diego Serraino, Carlo La Vecchia, Werner Garavello, Cristina Canova, Lorenzo Richiardi, Jolanta Lissowska, Tamas Pandics, Tom Dudding, Andy Ness, Steve Thomas, Miranda Pring, Karl Kelsey, Michael McClean, Patrick Bradshaw, Zuo-Feng Zhang, Hal Morgenstern, Laura Rozek, Gregory Wolf, Andrew Olshan, Geoffrey Liu, Rayjean Hung, Marta Vilensky, Marcos Brasilino de Carvalho, Rossana Verónica Mendonza López, Victor Wunsch-Filho, Paolo Boffetta, Mia Hashibe, Yuan-Chin Amy Lee, Stefania Boccia

The aim of this study is to investigate the prognostic role of body mass index (BMI) on survival from head and neck cancer (HNC). We performed a pooled analysis of studies included in the International Head and Neck Cancer Epidemiology consortium. We used Cox proportional hazards models to estimate the adjusted hazard ratios (HR) for overall survival and HNC-specific survival, and we stratified the results according to cancer site. The study included 10,177 patients from 10 studies worldwide. Underweight patients had lower overall survival (HR=1.69, 95% CI: 1.31-2.19) respect to those having normal weight with consistent results across the HNC sites. Overweight and obese patients had a favourable HNC-specific survival (HR=0.77 (95% CI: 0.70-0.84) and HR=0.80 (95% CI: 0.76-0.84), respectively), with heterogenous results according to HNC site. Our findings show that high BMI values at cancer diagnosis improved the survival rates in patients with HNC, especially among smokers. This association may be explained by residual confounding, reverse causation, and collider stratification bias, but may also suggest that a nutritional reserve may help patients survive HNC cancer.

本研究的目的是探讨身体质量指数(BMI)在头颈癌(HNC)患者生存中的预后作用。我们对国际头颈癌流行病学联盟的研究进行了汇总分析。我们使用Cox比例风险模型来估计总生存率和hnc特异性生存率的调整风险比(HR),并根据癌症部位对结果进行分层。该研究包括来自全球10项研究的10177名患者。与体重正常的患者相比,体重不足的患者的总生存率较低(HR=1.69, 95% CI: 1.31-2.19),在HNC各部位的结果一致。超重和肥胖患者有良好的HNC特异性生存(HR=0.77 (95% CI: 0.70-0.84)和HR=0.80 (95% CI: 0.76-0.84),根据HNC部位不同结果不同。我们的研究结果表明,癌症诊断时的高BMI值提高了HNC患者的生存率,尤其是吸烟者。这种关联可以用残留混杂、反向因果关系和碰撞分层偏差来解释,但也可能表明营养储备可能有助于HNC癌症患者存活。
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引用次数: 0
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American journal of cancer research
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