Prognostic marker

预后标记
  • 文章类型: Journal Article
    目的:治疗肺癌时,有必要识别早期治疗失败,以便及时进行治疗调整。这项研究的目的是研究化疗和贝伐单抗治疗期间肿瘤扩散的变化是否可以作为治疗失败的预测因子。
    方法:前瞻性单臂,开放标签,临床试验于2014年9月至2020年12月进行,纳入IV期非小细胞肺癌(NSCLC)患者.患者接受化疗-抗血管生成联合治疗。基线时进行弥散加权磁共振成像(DW-MRI),两个,四,开始治疗后16周。将治疗前和治疗后MRI之间的表观扩散系数(ADC)值的差异记录为Delta值(ΔADC)。我们评估了ΔADC是否可以作为总生存期(OS)的预后生物标志物,有五年的随访。
    结果:18例患者纳入最终分析。ΔADC值≥-3的患者表现出明显更长的OS,HR为0.12(95%CI;0.03-0.61;p=0.003)ΔADC值≥-3的患者的中位OS为18个月,(95%C.I;7-46)与ΔADC值<-3的那些中的7个月(95%C.I;5-9)相比。
    结论:我们的研究结果表明,肿瘤ADC值的早期变化,可能表示OS更长。因此,DW-MRI可以作为早期生物标志物,用于评估接受化疗联合抗血管生成治疗的患者的治疗反应。
    OBJECTIVE: When treating Lung Cancer, it is necessary to identify early treatment failure to enable timely therapeutic adjustments. The Aim of this study was to investigate whether changes in tumor diffusion during treatment with chemotherapy and bevacizumab could serve as a predictor of treatment failure.
    METHODS: A prospective single-arm, open-label, clinical trial was conducted between September 2014 and December 2020, enrolling patients with stage IV non-small cell lung cancer (NSCLC). The patients were treated with chemotherapy-antiangiogenic combination. Diffusion weighted magnetic resonance imaging (DW-MRI) was performed at baseline, two, four, and sixteen weeks after initiating treatment. The differences in apparent diffusion coefficient (ADC) values between pre- and post-treatment MRIs were recorded as Delta values (ΔADC). We assessed whether ΔADC could serve as a prognostic biomarker for overall survival (OS), with a five year follow up.
    RESULTS: 18 patients were included in the final analysis. Patients with a ΔADC value ≥ -3 demonstrated a significantly longer OS with an HR of 0.12 (95 % CI; 0.03- 0.61; p = 0.003) The median OS in patients with a ΔADC value ≥ -3 was 18 months, (95 % C.I; 7-46) compared to 7 months (95 % C.I; 5-9) in those with a ΔADC value < -3.
    CONCLUSIONS: Our findings suggest that early changes in tumor ADC values, may be indicative of a longer OS. Therefore, DW-MRI could serve as an early biomarker for assessing treatment response in patients receiving chemotherapy combined with antiangiogenic therapy.
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  • 文章类型: Journal Article
    炎症性肠病(IBD),包括克罗恩病和溃疡性结肠炎,表现出广泛的肠道和肠道外表现,这使得患者身体不活跃,生活质量受损。已经发现,身体活动是改善那些患者的生活质量的非药物干预。Irisin是运动过程中肌肉收缩分泌的肌细胞因子之一,可用作评估IBD患者身体活动的抗炎生物标志物。此外,实验研究表明,外源性irisin可显著降低实验性结肠炎患者的炎症指标和肠黏膜组织学变化。此外,irisin会改变微生物群的多样性。因此,内源性或外源性irisin,通过它的抗炎作用,将改善IBD患者的健康状况,并限制IBD患者的体育锻炼障碍。
    Inflammatory bowel disease (IBD), including Crohn\'s disease and ulcerative colitis, showed a wide spectrum of intestinal and extra-intestinal manifestations, which rendered the patients physically inactive and impaired their quality of life. It has been found that physical activity is a non-pharmacological intervention that improves the quality of life for those patients. Irisin is one member of the myokines secreted by muscle contraction during exercise and could be used as an anti-inflammatory biomarker in assessing the physical activity of IBD patients. In addition, experimental studies showed that exogenous irisin significantly decreased the inflammatory markers and the histological changes of the intestinal mucosa observed in experimental colitis. Furthermore, irisin produces changes in the diversity of the microbiota. Therefore, endogenous or exogenous irisin, via its anti-inflammatory effects, will improve the health of IBD patients and will limit the barriers to physical activity in patients with IBD.
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  • 文章类型: Journal Article
    背景:危重患者外周血中存在有核红细胞(NRBC)与不良预后相关。关于SARS-CoV-2诱发的急性呼吸窘迫综合征(ARDS)患者中NRBC的预测价值的证据仍然难以捉摸。这项研究的目的是评估NRBC在这些患者中的预测有效性。
    方法:评估SARS-CoV-2诱导的ARDS成年患者的每日NRBC值,并对其死亡率的预测效度进行统计学评估。根据ICU住院期间患者的最大NRBC值计算并根据Youden的方法进一步指定截止水平。根据这个截止值,我们进行了进一步分析,如logistic回归模型和生存率.
    结果:分析413例SARS-CoV-2致ARDS的危重患者。与存活的患者相比,未存活的患者在ICU住院期间的NRBC值明显更高(1090/μl[310;3883]vs.140/μl[20;500];p<0.0001)。重度ARDS患者(n=374)在ICU住院期间的NRBC值明显高于中度ARDS患者(n=38)(490/μl[120;1890]vs.30/μl[10;476];p<0.0001)。发现NRBC的截止水平≥500/μl可以最好地分层风险,并且与ICU住院时间更长有关(12[8;18]vs.18[13;27]天;p<0.0001)和更长的机械通气持续时间(10[6;16]vs.17[12;26]天;p<0.0001)。多变量校正的Logistic回归分析显示,NRBC≥500/µl是死亡率的独立危险因素(比值比(OR)4.72;95%置信区间(CI)2.95-7.62,p<0.0001)。NRBC值低于阈值500/μl的患者比高于阈值的患者具有显着的生存优势(中位生存32[95%CI8.7-43.3]与21天[95%CI18.2-23.8],对数秩检验,p<0.05)。在ICU入住期间达到NRBC阈值≥500/μl的患者的长期死亡率显着增加(中位生存期489天,对数秩检验,p=0.0029,风险比(HR)3.2,95%CI1.2-8.5)。
    结论:NRBCs预测SARS-CoV-2诱导的ARDS危重患者的死亡率,具有较高的预后能力。需要进一步的研究来确认NRBC的临床影响,以最终提高决策。
    BACKGROUND: The presence of nucleated red blood cells (NRBCs) in the peripheral blood of critically ill patients is associated with poor outcome. Evidence regarding the predictive value of NRBCs in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) remains elusive. The aim of this study was to evaluate the predictive validity of NRBCs in these patients.
    METHODS: Daily NRBC values of adult patients with SARS-CoV-2-induced ARDS were assessed and their predictive validity for mortality was statistically evaluated. A cut-off level based on the patient\'s maximum NRBC value during ICU stay was calculated and further specified according to Youden\'s method. Based on this cut-off value, further analyses such as logistic regression models and survival were performed.
    RESULTS: 413 critically ill patients with SARS-CoV-2-induced ARDS were analyzed. Patients who did not survive had significantly higher NRBC values during their ICU stay compared to patients who survived (1090/µl [310; 3883] vs. 140/µl [20; 500]; p < 0.0001). Patients with severe ARDS (n = 374) had significantly higher NRBC values during ICU stay compared to patients with moderate ARDS (n = 38) (490/µl [120; 1890] vs. 30/µl [10; 476]; p < 0.0001). A cut-off level of NRBC ≥ 500/µl was found to best stratify risk and was associated with a longer duration of ICU stay (12 [8; 18] vs. 18 [13; 27] days; p < 0.0001) and longer duration of mechanical ventilation (10 [6; 16] vs. 17 [12; 26] days; p < 0.0001). Logistic regression analysis with multivariate adjustment showed NRBCs ≥ 500/µl to be an independent risk factor of mortality (odds ratio (OR) 4.72; 95% confidence interval (CI) 2.95-7.62, p < 0.0001). Patients with NRBC values below the threshold of 500/µl had a significant survival advantage over those above the threshold (median survival 32 [95% CI 8.7-43.3] vs. 21 days [95% CI 18.2-23.8], log-rank test, p < 0.05). Patients who once reached the NRBC threshold of ≥ 500/µl during their ICU stay had a significantly increased long-term mortality (median survival 489 days, log-rank test, p = 0.0029, hazard ratio (HR) 3.2, 95% CI 1.2-8.5).
    CONCLUSIONS: NRBCs predict mortality in critically ill patients with SARS-CoV-2-induced ARDS with high prognostic power. Further studies are required to confirm the clinical impact of NRBCs to eventually enhance decision making.
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  • 文章类型: Journal Article
    近年来,C2ORF40已被确定为具有多种功能的肿瘤抑制基因,包括在细胞增殖中的作用,迁移,和衰老。探讨C2ORF40基因在不同肿瘤中的作用,我们使用多个数据库进行分析.与邻近的正常组织相比,C2ORF40在多种恶性肿瘤中表达下调,包括乳腺癌等肿瘤,结直肠癌,膀胱癌,肝细胞癌和前列腺癌。值得注意的是,该基因的低表达与低总生存率和无复发生存率显著相关.在特定的癌症中,包括结肠癌和前列腺癌,C2ORF40的表达与CAFs的浸润有关。C2ORF40还参与生物过程,例如细胞凋亡和蛋白质稳定性的调节。总之,C2ORF40有望成为泛癌症分析的预后标志物。
    In recent years, C2ORF40 has been identified as a tumor suppressor gene with multiple functions, including roles in cell proliferation, migration, and senescence. To explore the role of the C2ORF40 gene in different tumors, we used multiple databases for analysis. Compared to adjacent normal tissues, C2ORF40 is downregulated in a variety of malignant tumors, including tumors such as breast cancer, colorectal cancer, bladder cancer, hepatocellular carcinoma and prostate cancer. Notably, low expression of the gene is significantly associated with poor overall survival and relapse-free survival rates. In specific cancers including colon cancer and prostate cancer, the expression of C2ORF40 is correlated with the infiltration of CAFs. C2ORF40 is also involved in biological processes such as cell apoptosis and regulation of protein stability. In conclusion, C2ORF40 can hold promise as a prognostic marker for pan-cancer analysis.
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  • 文章类型: Journal Article
    背景:神经母细胞瘤(NB)是儿童时期最常见的实体瘤,并在交感神经系统中上升。这里,我们讨论了参与DNA损伤反应的H2AFX基因表达之间的关联的计算机分析,和786例NB患者的生存率。
    方法:从Cangelosi等人总结的公开可用数据集中检索了计算机基因表达。,包括发病时786例NB肿瘤的13,696个基因表达谱。通过Kaplan-Meier和Cox回归分析评估H2AFX(H2A组蛋白家族成员X)基因表达对无事件生存期(EFS)和总生存期(OS)的预后价值。主要结果在另一个公开访问的计算机数据库(NRC-283)上进行了验证,该数据库在283例NB患者中包含13,489个基因表达。然后通过免疫荧光在不同肿瘤分期的48个原代NB样品上测试H2AFX蛋白的表达。H2AFX作为癌基因的活性已通过在两个NB细胞系中沉默该分子在体外得到进一步验证,以MYCN扩增或不扩增为特征,并进行细胞生长和迁移测定。
    结果:观察到H2AFX表达与患者生存之间的强烈负相关,并通过对原发性NB组织切片的免疫荧光结果证实。Cox回归分析还显示H2AFX是EFS和OS的独立预测因子。基因沉默实验强烈提示H2AFX在NB细胞上的致癌作用,无论MYCN扩增。
    结论:H2AFX是不良NB的预后标志物,可被视为治疗干预的目标。
    BACKGROUND: Neuroblastoma (NB) is the most common solid tumour in childhood, and rises in the sympathetic nervous system. Here, we addressed the in silico analysis of the association between the expression of H2AFX gene involved in DNA damage response, and the survival of a cohort of 786 NB patients.
    METHODS: In silico gene expression was retrieved from the publicly available dataset summarised by Cangelosi et al., including 13,696 gene expression profiles of 786 NB tumours at onset of disease. The prognostic value of H2AFX (H2A histone family member X) gene expression for event-free survival (EFS) and overall survival (OS) was evaluated by Kaplan-Meier and Cox regression analysis. The main results were validated on another openly accessible in silico database (NRC-283) containing 13,489 gene expressions in 283 NB patients. The expression of H2AFX protein was then tested by immunofluorescence on 48 primary NB samples of different tumour stages. H2AFX activity as an oncogene has been further validated in vitro by silencing the molecule in two NB cell lines, characterised by MYCN amplified or not, and performing cell growth and migration assays.
    RESULTS: A strong inverse association between H2AFX expression and patients\' survival was observed and confirmed by immunofluorescence results on primary NB tissue sections. Cox regression analysis also disclosed H2AFX as an independent predictor of EFS and OS. The gene-silencing experiments strongly suggested an oncogenic role for H2AFX on NB cells, regardless of MYCN amplification.
    CONCLUSIONS: H2AFX is a prognostic marker for unfavourable NB and could be considered a target for therapeutic interventions.
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  • 文章类型: Journal Article
    目的:全身炎症与癌症的发生和发展有关。炎症标志物已被确定为许多恶性肿瘤的预后指标。这项研究探讨了初次和术后中性粒细胞-淋巴细胞比率(NLR)和血小板-淋巴细胞比率(PLR)对软组织肉瘤(STS)患者的无复发生存率(RFS)和总生存率(OS)的预后相关性。
    方法:我们纳入了2004年至2018年期间在Kyungpook国立大学Chilgok医院接受广泛和根治性切除术的89例STS患者。使用多变量Cox比例模型计算RFS和OS的Kaplan-Meier曲线。
    结果:共有67例(75.3%)患者表现出较高的初始NLR(≥4.1),65例(75.3%)患者表现出较高的初始PLR(≥231)。在单变量和多变量分析中,初始PLR比率升高与RFS(p=0.017)和OS(p=0.003)降低显著相关.高PLR(PLR>231)患者的中位RFS为24个月,而PLR低(PLR≤231)者的中位RFS为96个月.高PLR和低PLR组的中位OS分别为50和298个月,分别。此外,高的术后PLR比率与RFS(p=0.001)和OS(p=0.038)降低相关.
    结论:术前和术后PLR比值可作为STS患者接受手术治疗的肿瘤预后的经济有效指标。
    OBJECTIVE: Systemic inflammation has been implicated in the development and progression of cancer. Inflammatory markers have been identified as prognostic indicators in numerous malignancies. This study explored the prognostic relevance of the initial and postoperative neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) on relapse-free survival (RFS) and overall survival (OS) in patients with soft-tissue sarcoma (STS) who underwent curative resection.
    METHODS: We included 89 patients with STS who underwent extensive and radical resection at the Kyungpook National University Chilgok Hospital between 2004 and 2018. Kaplan-Meier curves for RFS and OS were calculated using multivariate Cox proportional models.
    RESULTS: A total of 67 (75.3%) patients demonstrated a high initial NLR (≥4.1) and 65 (75.3%) showed a high initial PLR (≥231). In the univariate and multivariate analyses, an elevated initial PLR ratio was significantly associated with a decreased RFS (p=0.017) and OS (p=0.003). Patients with a high PLR (PLR >231) had a median RFS of 24 months, whereas those with a low PLR (PLR ≤231) had a median RFS of 96 months. The median OS was 50 and 298 months for the high PLR and low PLR groups, respectively. Furthermore, a high postoperative PLR ratio was associated with a decreased RFS (p=0.001) and OS (p=0.038).
    CONCLUSIONS: Preoperative and postoperative PLR ratio can be used as a cost-effective prognostic marker for oncologic outcomes in patients with STS who undergo surgery.
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  • 文章类型: Journal Article
    背景:本研究旨在评估总肿瘤体积(TTV)对结直肠癌肝转移(CRLM)患者早期复发(6个月内)和总生存期(OS)的预后价值,采用诱导全身治疗,然后进行完全局部治疗。
    方法:纳入了多中心随机3期CAIRO5试验(NCT02162563)中最初不可切除的CRLM患者,这些患者接受了诱导全身治疗,然后进行了局部治疗。使用全身治疗前后的CT扫描计算基线TTV和对全身治疗反应的TTV变化。并评估其增加的预后价值。这些发现在三级中心接受治疗的患者的外部队列中得到了验证。
    结果:总计,包括215例CAIRO5患者。在多变量分析中,基线TTV和TTV的绝对变化与早期复发(分别为P=0.005和P=0.040)和OS显着相关(分别为P=0.024和P=0.006),而RECIST1.1对早期复发(P=0.88)和OS(P=0.35)无预后。在验证队列中(n=85),在多变量分析中,基线TTV和TTV的绝对变化仍然是早期复发的预后(分别为P=0.041和P=0.021)和OS(分别为P<0.0001和P=0.012),并显示出比常规临床病理变量增加的预后价值(增加C统计量,0.06;95%CI,0.02至0.14;P=0.008)。
    结论:在接受最初不可切除的CRLM的完全局部治疗的患者中,总肿瘤体积对早期复发和OS具有强烈的预后。在CAIRO5试验和验证队列中。相比之下,RECIST1.1对早期复发和OS均未显示预后价值。
    BACKGROUND: This study aimed to assess the prognostic value of total tumor volume (TTV) for early recurrence (within 6 months) and overall survival (OS) in patients with colorectal liver metastases (CRLM), treated with induction systemic therapy followed by complete local treatment.
    METHODS: Patients with initially unresectable CRLM from the multicenter randomized phase 3 CAIRO5 trial (NCT02162563) who received induction systemic therapy followed by local treatment were included. Baseline TTV and change in TTV as response to systemic therapy were calculated using the CT scan before and the first after systemic treatment, and were assessed for their added prognostic value. The findings were validated in an external cohort of patients treated at a tertiary center.
    RESULTS: In total, 215 CAIRO5 patients were included. Baseline TTV and absolute change in TTV were significantly associated with early recurrence (P = 0.005 and P = 0.040, respectively) and OS in multivariable analyses (P = 0.024 and P = 0.006, respectively), whereas RECIST1.1 was not prognostic for early recurrence (P = 0.88) and OS (P = 0.35). In the validation cohort (n = 85), baseline TTV and absolute change in TTV remained prognostic for early recurrence (P = 0.041 and P = 0.021, respectively) and OS in multivariable analyses (P < 0.0001 and P = 0.012, respectively), and showed added prognostic value over conventional clinicopathological variables (increase C-statistic, 0.06; 95 % CI, 0.02 to 0.14; P = 0.008).
    CONCLUSIONS: Total tumor volume is strongly prognostic for early recurrence and OS in patients who underwent complete local treatment of initially unresectable CRLM, both in the CAIRO5 trial and the validation cohort. In contrast, RECIST1.1 did not show prognostic value for neither early recurrence nor OS.
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  • 文章类型: Journal Article
    随着基因检测技术的发展,我们发现了许多不同的基因,lncRNA就是其中之一。LncRNAs是指长度超过200bp的非蛋白质编码RNA分子。是LUAD等人类恶性疾病研究的重点之一。LncRNAs作为癌基因或抑制剂调节肿瘤的发生和进展。LncRNAs的差异表达通过影响细胞增殖促进或抑制肺腺癌的进展,转移,入侵,和细胞凋亡,从而影响患者的预后和生存率。因此,LncRNAs可以作为癌症诊断和治疗的潜在靶点。通过检测肿瘤标志物对该病进行早期诊断。由于肺腺癌早期不易诊断,肿瘤标志物容易忽视,LncRNAs在肺腺癌的诊断和治疗中起着重要作用。本文的主要目的是总结LncRNAs对肺腺癌的已知作用,LncRNAs差异表达对肺腺癌进展的影响,以及相关的信号转导通路。并为今后肺腺癌相关LncRNAs的研究提供新的思路。
    With the development of gene testing technology, we have found many different genes, and lncRNA is one of them. LncRNAs refer to a non-protein coding RNA molecule with a length of more than 200bp, which is one of the focuses of research on human malignant diseases such as LUAD. LncRNAs act as an oncogene or inhibitor to regulate the occurrence and progression of tumors. The differential expression of LncRNAs promotes or inhibits the progression of lung adenocarcinoma by affecting cell proliferation, metastasis, invasion, and apoptosis, thus affecting the prognosis and survival rate of patients. Therefore, LncRNAs can be used as a potential target for diagnosis and treatment of cancer. The early diagnosis of the disease was made through the detection of tumor markers. Because lung adenocarcinoma is not easy to diagnose in the early stage and tumor markers are easy to ignore, LncRNAs play an important role in the diagnosis and treatment of lung adenocarcinoma. The main purpose of this article is to summarize the known effects of LncRNAs on lung adenocarcinoma, the effect of differential expression of LncRNAs on the progression of lung adenocarcinoma, and related signal transduction pathways. And to provide a new idea for the future research of lung adenocarcinoma-related LncRNAs.
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  • 文章类型: Journal Article
    有机磷中毒对人类健康构成重大威胁,需要准确的预后标志物来及时干预和改善预后。这篇综述评估了中性粒细胞与淋巴细胞比率(NLR)作为急性有机磷中毒(AOPP)预后指标的潜力。对现有文献的综合分析显示,NLR值升高与中毒严重程度增加和不良临床结局相关。包括死亡率和发病率。NLR评估提供了超越传统标志物的有价值的预后信息,辅助风险分层,指导临床决策。将NLR纳入临床实践有望通过早期识别高风险个体和量身定制的治疗干预措施来优化患者护理。需要进一步的研究来验证NLR在较大患者队列中的实用性,并将其标准化纳入临床指南。利用NLR作为预后工具可以增强风险分层,优化治疗策略,并最终改善AOPP的结果。
    Organophosphorus poisoning (OPP) poses a significant threat to human health, necessitating accurate prognostic markers for timely intervention and improved outcomes. This review evaluates the potential of the neutrophil-to-lymphocyte ratio (NLR) as a prognostic indicator in acute organophosphorus poisoning (AOPP). A comprehensive analysis of existing literature reveals that elevated NLR values correlate with increased severity of poisoning and adverse clinical outcomes, including mortality and morbidity. NLR assessment offers valuable prognostic information beyond traditional markers, aiding risk stratification and guiding clinical decision-making. Integration of NLR into clinical practice holds promise for optimizing patient care through the early identification of high-risk individuals and tailored therapeutic interventions. Further research is needed to validate the utility of NLR in larger patient cohorts and standardize its incorporation into clinical guidelines. Leveraging NLR as a prognostic tool can enhance risk stratification, optimize treatment strategies, and ultimately improve outcomes in AOPP.
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  • 文章类型: Journal Article
    胆管癌(CCA)因其高度恶性而广为人知,快速发展,和有限的治疗选择。这项研究是对来自不同解剖位置的417个CCA样品的转录组数据进行的。比较脂质代谢相关基因和免疫相关基因作为CCA分类器的效果。关键基因来源于MVI亚型和较好的分子亚型。在MVI阳性组中,上皮间质转化(EMT)和细胞周期等途径显着激活。根据脂质代谢(免疫)相关基因将CCA患者分为三(四)种亚型,在脂质代谢C1,免疫C2和免疫C4中观察到更好的预后。IPTW分析发现,纠正前后脂代谢-C1的预后明显优于脂代谢-C2+C3的预后。最终选择KRT16作为关键基因。KRT16的敲除抑制增殖,CCA细胞的迁移和侵袭。
    Cholangiocarcinoma (CCA) is widely noted for its high degree of malignancy, rapid progression, and limited therapeutic options. This study was carried out on transcriptome data of 417 CCA samples from different anatomical locations. The effects of lipid metabolism related genes and immune related genes as CCA classifiers were compared. Key genes were derived from MVI subtypes and better molecular subtypes. Pathways such as epithelial mesenchymal transition (EMT) and cell cycle were significantly activated in MVI-positive group. CCA patients were classified into three (four) subtypes based on lipid metabolism (immune) related genes, with better prognosis observed in lipid metabolism-C1, immune-C2, and immune-C4. IPTW analysis found that the prognosis of lipid metabolism-C1 was significantly better than that of lipid metabolism-C2 + C3 before and after correction. KRT16 was finally selected as the key gene. And knockdown of KRT16 inhibited proliferation, migration and invasion of CCA cells.
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