Clinical application value of long non-coding RNAs signatures of genomic instability in predicting prognosis of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)presents challenges due to its high recurrence and metastasis rates and poor prognosis.While current clinical diagnostic and prognostic indicators exist,their accuracy remains imperfect due to their biol-ogical complexity.Therefore,there is a quest to identify improved biomarkers for HCC diagnosis and prognosis.By combining long non-coding RNA(lncRNA)expression and somatic mutations,Duan et al identified five representative lncRNAs from 88 lncRNAs related to genomic instability(GI),forming a GI-derived lncRNA signature(LncSig).This signature outperforms previously re-ported LncSig and TP53 mutations in predicting HCC prognosis.In this editorial,we comprehensively evaluate the clinical application value of such prognostic evaluation model based on sequencing technology in terms of cost,time,and practicability.Additionally,we provide an overview of various prognostic models for HCC,aiding in a comprehensive understanding of research progress in pro-gnostic evaluation methods.

Challenges related to clinical decision-making in hepatocellular carcinoma recurrence post-liver transplantation: Is there a hope?

Hepatocellular carcinoma(HCC)is a common liver malignancy and represents a serious cause of cancer-related mortality and morbidity.One of the favourable curative surgical therapeutic options for HCC is liver transplantation(LT)in selected patients fulfilling the known standard Milan/University of California San Francisco criteria which have shown better outcomes and longer-term survival.Despite careful adherence to the strict HCC selection criteria for LT in different transplant centres,the recurrence rate still occurs which could negatively affect HCC patients’survival.Hence HCC recurrence post-LT could predict patients’survival and prognosis,depending on the exact timing of recurrence after LT(early or late),and whether intra/extrahepatic HCC recurrence.Several factors may aid in such a complication,particularly tumour-related criteria including larger sizes,higher grades or poor tumour differentiation,microvascular invasion,and elevated serum alpha-fetoprotein.Therefore,managing such cases is challenging,different therapeutic options have been proposed,including curative surgical and ablative treatments that have shown better outcomes,compared to the palliative locoregional and systemic therapies,which may be helpful in those with unresectable tumour burden.To handle all these issues in our review.

Expression patterns of cluster of differentiation 147 impact the prognosis of hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)has very low overall survival.According to global cancer statistics,approximately 905677 new cases were reported in 2020,with at least 830180 of them being fatal.Cluster of differentiation 147(CD147)is a novel,transmembrane glycoprotein that is expressed in a wide variety of tumor cells and plays an important role in various stages of tumor development.Based on the reports described previously,we theorize that CD147 may be used as a novel biological indicator to predict the prognosis of HCC.To study this possibility,expression profiles of CD147 and corresponding clinical data from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases were analyzed,and a hazard ratio(HR)was established.AIM To explore the pattern of CD147 expression and its applicability in the prognosis of HCC.To establish HRs and probability points for predicting the prognosis of HCC by correlating CD147 expression with clinical characteristics.To determine if CD147 can be a reliable biomarker in HCC prognosis.METHODS The CD147 expression profile in HCC and corresponding clinical data were obtained from TCGA database.The expression patterns of CD147 were then validated by analyzing data from the GEO database.In addition,CD147 immunohistochemistry in HCC was obtained from the Human Protein Atlas.CD147 expression patterns and clinical characteristics in the prognosis of HCC were analyzed by accessing the UALCAN web resource.Accuracy,sensitivity,and specificity of the CD147 expression profile in predictive prognosis were determined by the time-dependent receiver operating characteristic(ROC)curves.Kaplan-Meier curves were plotted to estimate the HR of survival in HCC.Univariate and multivariate Cox regression proportional hazards analyses of CD147 expression levels and clinical characteristics as prognostic factors of HCC were performed.Nomograms were used to establish probability points and predict prognosis.RESULTS Data from TCGA and GEO databases revealed that CD147 was significantly overexpressed in HCC(P=1.624×10^(-12) and P=1.2×10^(-5),respectively).The expression of CD147 and prognosis of HCC were significantly correlated with the clinical characteristics of HCC as per the data from the UALCAN web resource(P<0.05).Kaplan-Meier analysis of CD147 expression in HCC revealed that the high expression groups showed poor prognosis and an HR of survival>1[log-rank test,P=0.000542,HR(in high expression group):1.856,95%confidence interval(CI):1.308 to 2.636].ROC curves were plotted to analyze the 1-year,3-year,and 5-year survival rates.The area under the ROC curve values were 0.675(95%CI:0.611 to 0.740),0.623(95%CI:0.555 to 0.692),and 0.664(95%CI:0.582 to 9.745),respectively.Univariate Cox analysis of CD147 expression and clinical characteristics of HCC and multivariate Cox analysis of CD147 patterns and pathological tumor-node-metastasis stage showed significant differences(univariate Cox,P=0.00013,HR:1.424,95%CI:1.884 to 1.707 and P=0.00066,HR:1.376,95%CI:1.145 to 1.654,respectively;multivariate Cox,P=0.00578,HR:1.507,95%CI:1.126 to 2.018 and P=0.00336,HR:1.443,95%CI:1.129 to 1.844,respectively).Nomograms were plotted to establish the probability points and predict prognosis.The total points ranged from 0 to 180,and the C-index value was 0.673(95%CI:0.600 to 1.000,P<0.01).CONCLUSION Overexpression of CD147 was correlated with poor prognosis in HCC.The CD147 expression profile combined with clinical characteristics can reliably predict the prognosis of HCC.CD147 can serve as a biomarker to predict the prognosis of HCC.

Clinic pathological features and prognosis of metaplastic breast carcinoma

Objective:To investigate clinic pathological peculiarities and evaluate the prognosis of metaplastic breast carcinoma.Methods:Patients with metaplastic breast carcinoma at the First Affiliated Hospital of Zhejiang University and Guangxing Hospital Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine from 2008 to 2013 were retrospectively selected.Results:A total of 73 female patients were reviewed,including 41 cases of purely epithelial type and 32 cases of mixed epithelial and mesenchymal type.Median tumor size was 4.6cm.Forty-three patients(58.8%)presented with lymph node metastasis,84.9%of cases were in advanced TNM stage,and 60.2%of cases were overexpressed by Ki-67.At a median follow-up of 59 months,median overall survival and disease-free survival were 59.7 and 43.9 months,respectively.Five-year overall survival rate was 45.2%and disease-free survival rate was 30.1%,and 76.7%of patients had recurrence or metastasis.Univariate analysis showed that tumor size,lymph node,and radiotherapy were associated with overall survival and disease-free survival(P<0.05),while Ki-67 over-expression was correlated with overall survival(P<0.05).With multivariate analysis,tumor size,lymph node,and radiotherapy affected prognosis(P<0.05);however,pathological typing was not an independent prognostic factor(P>0.05).Conclusion:Metaplastic breast carcinoma is a rare malignant tumor with large tumor,high lymph node metastasis rate,staging relatively late,high local recurrence and distant metastasis rate.The treatment follows the principle of comprehensive treatment based on surgery,but the prognosis is poor.Tumor size,lymph node,and radiotherapy treatment affect the prognosis.Overexpression of Ki-67 can be used as a potential diagnostic,therapeutic and prognostic indicator for metaplastic breast cancer.

Value of α-fetoprotein in association with clinicopathological features of hepatocellular carcinoma

AIM:To explore the relationship between α-fetoprotein(AFP) and various clinicopathological variables and different staging system of hepatocellular carcinoma(HCC) thoroughly.METHODS:A retrospective cohort study of consecutive patients diagnosed with HCC between January 2008 and December 2009 in West China Hospital was enrolled in our study.The association of serum AFP values with the HCC clinicopathological features was analysed by univariate and multivariate analysis,such as status of hepatitis B virus(HBV) infection,tumor size,tumor number,vascular invasion and degree of tumor differentiation.Also,patients were divided into four groups at the time of enrollment according to different cutoff values for serum value of AFP(≤ 20 μg/L,21-400 μg/L,401-800 μg/L,and ≥ 801 μg/L),to compare the positive rate of patient among four groups stratified by various clinicopathological variables.And the correlation of different kinds of tumor staging systems,such as TNM,Barcelona Clinic Liver Cancer(BCLC) staging classification and China staging,were compared with the serum concentration of AFP.RESULTS:A total of 2304 HCC patients were enrolled in this study totally;the mean serum level of AFP was 555.3 ± 546.6 μg/L.AFP levels were within the normal range(< 20 μg/L) in 27.4%(n = 631) of all the cases.81.4%(n = 1875) patients were infected with HBV,and those patients had much higher serum AFP level compared with non-HBV infection ones(573.9 ± 547.7 μg/L vs 398.4 ± 522.3 μg/L,P < 0.001).The AFP level in tumors ≥ 10 cm(808.4 ± 529.2 μg/L) was significantly higher(P < 0.001) than those with tumor size 5-10 cm(499.5 ± 536.4 μg/L) and with tumor size ≤ 5 cm(444.9 ± 514.2 μg/L).AFP levels increased significantly in patients with vascular invasion(694.1 ± 546.9 μg/L vs 502.1 ± 543.1 μg/L,P < 0.001).Patients with low tumor cell differentiation(559.2 ± 545.7 μg/L) had the significantly(P = 0.007) highest AFP level compared with high differentiation(207.3 ± 420.8 μg/L) and intermediate differentiation(527.9 ± 538.4 μg/L).In the multiple variables analysis,low tumor cell differentiation [OR 6.362,95%CI:2.891-15.382,P = 0.006] and tumor size(≥ 10 cm)(OR 5.215,95%CI:1.426-13.151,P = 0.012) were independent predictors of elevated AFP concentrations(AFP > 400 μg/L).Serum AFP levels differed significantly(P < 0.001) in the D stage of BCLC(625.7 ± 529.8 μg/L) compared with stage A(506.2 ± 537.4 μg/L) and B(590.1 ± 551.1 μg/L).CONCLUSION:HCC differentiation,size and vascular invasion have strong relationships with AFP,poor differentiation and HCC size ≥ 10 cm are independent predictors of elevated AFP.BCLC shows better relationship with

Grey zone in the Barcelona Clinic Liver Cancer Classification for hepatocellular carcinoma: Surgeons' perspective

Hepatocellular carcinoma(HCC) is the sixth most common cancer and the third most common cause of cancer-related deaths worldwide. The Barcelona Clinic Liver Cancer(BCLC) classification has been endorsed as the optimal staging system and treatment algorithm for HCC by the European Association for the Study of Liver Disease and the American Association for the Study of Liver Disease. However, in real life, the majority of patients who are not considered ideal candidates based on the BCLC guideline still were performed hepatic resection nowadays, which means many hepatic surgeons all around the world do not follow the BCLC guidelines. The accuracy and application of the BCLC classification has constantly been challenged by many clinicians. From the surgeons' perspectives, we herein put forward some comments on the BCLC classification concerning subjectivity of the assessment criteria, comprehensiveness of the staging definition and accuracy of the therapeutic recommendations. We hope to further discuss with peers and colleagues with the aim to make the BCLC classification more applicable to clinical practice in the future.

Barcelona Clinic Liver Cancer outperforms Hong Kong Liver Cancer staging of hepatocellular carcinoma in multiethnic Asians: Real-world perspective

To compare the Barcelona Clinic Liver Cancer (BCLC) and Hong Kong Liver Cancer (HKLC) classification systems when applied to HCC patients from the largest tertiary-level centre in Singapore.METHODSOne thousand two hundred and seventy hepatocellular carcinoma (HCC) patients prospectively enrolled in a tertiary-level centre registry in Singapore since 1988 were studied. Patients were grouped into their respective BCLC and HKLC stages. Data such as demography, aetiology of HCC and type of treatment were collected. Survival data was based on census with the National Registry of Births and Deaths on 31st October 2015. Statistical analyses were done using SPSS version 21 (Chicago, IL, United States). Survival analyses were done by the Kaplan-Meier method. Differences in survival rates were compared using the log-rank test.RESULTSThe median age at presentation was 63 years (range 13-94); male 82.4%; Chinese 89.4%, Malay 7.1%, Indian, 2.8%. Hepatitis B was the predominant aetiology (75.0%; Hepatitis C 7.2%, Hepatitis B and C co-infection 3.8%, non-viral 14.0%). Both BCLC and HKLC staging systems showed good separation with overall log rank test confirming significant survival differences between stages in our cohort (P < 0.001). 206 out of the 240 patients (85.8%) assigned for curative treatment by the BCLC treatment algorithm received curative therapy for HCC [Stage 0 93.2% (68/73); Stage A 82.6% (138/167)]. In contrast, only 341/558 (61.1%) patients received curative treatment despite being assigned for curative treatment by the HKLC treatment algorithm [Stage I 72.7% (264/363); Stage II 40.2% (66/164); Stage Va 35.5% (11/31)]. Patients who were assigned to curative treatment by HKLC but did not receive curative treatment had significantly poorer ECOG (P < 0.001), higher Child-Pugh status (P < 0.001) and were older (median age 66 vs 61, P < 0.001) than those who received curative therapy. Median overall survival in patients assigned to curative treatment groups by BCLC and HKLC were 6.1 and 2.6 years respectively (P < 0.001). When only patients receiving curative treatment were analyzed, BCLC still predicted overall median survival better than HKLC (7.1 years vs 5.5 years, P = 0.037).CONCLUSIONBCLC performs better than HKLC in our multiethnic Asian population in allocating patients to curative treatment in a real-life situation as well as in predicting survival.

The prognostic molecular markers in hepatocellular carcinoma

The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) levels, as well as intratumor microvessel density (MVD) have been evaluated and found to be of prognostic significance. Body fluid (particularly blood and urinary) testing for biomarkers is easily accessible and useful in clinical patients. The prognostic significance of circulating DNA in plasma or serum, and its genetic alterations in HCC are other important trends. More attention should be paid to these two areas in future. As the progress of the human genome project advances, so does a clearer understanding of tumor biology, and more and more new prognostic markers with high sensitivity and specificity will be found and used in clinical assays. However, the combination of some items, i.e., the pathological features and some biomarkers mentioned above, seems to be more practical for now.

Staging systems of hepatocellular carcinoma:A review of literature

Hepatocellular carcinoma(HCC)is a major health problem with a high incidence and mortality all over the world.Natural history of HCC is severe and extremely variable,and prognostic factors influencing outcomes are incompletely defined.Over time,many staging and scoring systems have been proposed for the classification and prognosis of patients with HCC.Currently,the non-ideal predictive performance of existing prognostic systems is secondary to their inherent limitations,as well as to a non-universal reproducibility and transportability of the results in different populations.New serological and histological markers are still under evaluation with promising results,but they require further evaluation and external validation.The aim of this review is to highlight the main tools for assessing the prognosis of HCC and the main concerns,pitfalls and warnings regarding its staging systems currently in use.

Enhancement parameters of contrast-enhanced computed tomography for pancreatic ductal adenocarcinoma: Correlation with pathologic grading

BACKGROUND Pancreatic ductal adenocarcinoma(PDA)is a malignancy with a high mortality rate and short survival time.The conventional computed tomography(CT)has been worldwide used as a modality for diagnosis of PDA,as CT enhancement pattern has been thought to be related to tumor angiogenesis and pathologic grade of PDA.AIM To evaluate the relationship between the pathologic grade of pancreatic ductal adenocarcinoma and the enhancement parameters of contrast-enhanced CT.METHODS In this retrospective study,42 patients(Age,mean±SD:62.43±11.42 years)with PDA who underwent surgery after preoperative CT were selected.Two radiologists evaluated the CT images and calculated the value of attenuation at the aorta in the arterial phase and the pancreatic phase(VAarterial and VApancreatic)and of the tumor(VTarterial and VTpancreatic)by finding out four regions of interest.Ratio between the tumor and the aorta enhancement on the arterial phase and the pancreatic phase(TARarterial and TARpancreatic)was figured out through dividing VT arterial by VAarterial and VTpancreatic by VApancreatic.Tumor-to-aortic enhancement fraction(TAF)was expressed as the ratio of the difference between attenuation of the tumor on arterial and parenchymal images to that between attenuation of the aorta on arterial and pancreatic images.The Kruskal-Wallis analysis of variance and Mann-Whitney U test for statistical analysis were used.RESULTS Forty-two PDAs(23 men and 19 women)were divided into three groups:Welldifferentiated(n=13),moderately differentiated(n=21),and poorly differentiated(n=8).TAF differed significantly between the three groups(P=0.034)but TARarterial(P=0.164)and TARpancreatic(P=0.339)did not.The median value of TAF for poorly differentiated PDAs(0.1011;95%CI:0.01100-0.1796)was significantly higher than that for well-differentiated PDAs(0.1941;95%CI:0.1463-0.3194).CONCLUSION Calculation of TAF might be useful in predicting the pathologic grade of PDA.

动脉期不规则环形强化肝细胞癌的病理学特征及早期复发预后

目的探讨钆塞酸二钠增强MRI动脉期不规则环形强化肝细胞癌(IRE-HCC)的病理学特征,分析其根治切除术后早期复发情况。资料与方法回顾性收集2015年2月—2021年9月在南通市第三人民医院就诊且经手术病理证实的HCC 131例。依据钆塞酸二钠增强MRI动脉期强化方式分为IRE-HCC和非IRE-HCC。比较两组患者的临床、病理及影像资料。采用Logistic回归分析与IRE-HCC相关的临床、病理与影像学特征,Kaplan-Meier法评估HCC术后2年内早期无复发生存率,Cox回归分析HCC术后早期复发的危险因素。结果CK19(OR=9.027,95%CI 2.533~32.170,P=0.001)、微血管侵犯(OR=3.606,95%CI 1.024~12.701,P=0.046)和扩散加权成像靶征(OR=10.370,95%CI 3.046~35.303,P=0.000)与IRE-HCC相关。IRE-HCC术后2年累积无复发生存率(24.1%)显著低于非IRE-HCC(55.9%,χ^(2)=19.971,P=0.000)。微血管侵犯(HR=2.206,95%CI1.152~4.226,P=0.017)和IRE(HR=2.454,95%CI 1.408~4.275,P=0.002)是HCC术后早期复发的独立预测指标。结论IREHCC与CK19、微血管侵犯和扩散加权成像靶征相关,且术后早期复发率高、预后差。

EGFR突变NSCLC组织LncRNA TCF7L2表达及临床病理特征和预后分析

目的 探究长链非编码RNA(LncRNA)转录因子7类似物2(TCF7L2)在表皮生长因子受体基因(EGFR)突变的非小细胞肺癌(NSCLC)组织表达及其与病人临床病理特征和预后相关性。方法 选取2019年3月—2021年6月河北北方学院附属第一医院治疗的EGFR突变NSCLC病人104例为研究对象,分别取其癌组织和癌旁组织应用逆转录PCR(RT-PCR)检测LncRNA TCF7L2的表达,比较不同组织TCF7L2表达及其与临床病理特征和预后的相关性。结果 RT-PCR检测结果显示,癌组织中LncRNA TCF7L2表达量显著高于癌旁组织(t=12.410,P<0.05)。与LncRNA TCF7L2低表达病人比较,高表达者发生淋巴结转移更多、肿瘤体积更大(χ^(2)=4.579、7.762,P<0.05);LncRNA TCF7L2高表达病人6、9和12个月的生存率较低,但差异均无统计学意义(P>0.05)。结论 LncRNA TCF7L2在EGFR突变NSCLC病人癌组织表达高于癌旁组织,且TCF7L2高表达病人的淋巴结转移风险较高、肿瘤体积较大,其生存率可能较低。

鼻咽癌组织SNHG15和LINC00261的表达及其临床意义

目的:探讨鼻咽癌中小核仁RNA宿主基因15(SNHG15)和LINC00261的表达水平及其临床意义。方法:收集2018年1月至2020年2月本院93例行鼻咽癌根治性切除术患者的鼻咽癌组织和癌旁组织样本以及临床资料;培养鼻咽癌CNE-1细胞和正常鼻咽部上皮NP69细胞,分为空白对照组、shRNA-NC组(转染SNHG15对照)、SNHG15-shRNA组(转染SNHG15)、pcDNA-NC组(转染LINC00261对照)、LINC00261-pcDNA组(转染LINC00261);采用RT-qPCR检测SNHG15和LINC00261表达水平;采用CCK-8和克隆形成实验检测各组细胞的增殖情况;采用Pearson法分析组织中SNHG15和LINC00261表达水平的相关性;采用Kaplan-Meier法分析鼻咽癌组织SNHG15和LINC00261表达水平与患者预后的关系;采用多因素Cox回归分析影响鼻咽癌患者预后的相关因素。结果:鼻咽癌组织中SNHG15表达水平高于癌旁组织,LINC00261表达水平则低于癌旁组织;鼻咽癌组织中SNHG15和LINC00261表达水平呈负相关。CNE-1细胞中SNHG15表达水平高于NP69细胞,LINC00261表达水平则低于NP69细胞;SNHG15-shRNA组和LINC00261-pcDNA组CNE-1细胞克隆形成数量均低于空白对照组、shRNA-NC组及pcDNA-NC组,细胞增殖能力降低。不同SNHG15和LINC00261表达水平的鼻咽癌患者年龄、肿瘤直径及组织学类型差异无统计学意义,而SNHG15高表达组及LINC00261低表达组发生淋巴结转移、TNM分期为Ⅲ+Ⅳ期的患者所占比例显著高于SNHG15低表达组及LINC00261高表达组;SNHG15低表达患者3年生存率(84.78%)显著高于SNHG15高表达患者(65.95%),LINC00261低表达患者3年生存率(63.04%)显著低于LINC00261高表达患者(87.23%)。结论:鼻咽癌组织中SNHG15和LINC00261表达与患者临床病理特征及预后密切相关,淋巴结转移、TNM分期及SNHG15是鼻咽癌患者死亡的危险因素,而LINC00261是鼻咽癌患者死亡的保护因素。

39例肺肉瘤样癌临床病理特征及预后分析

背景与目的肺肉瘤样癌(pulmonary sarcomatoid carcinoma,PSC)是非小细胞肺癌(non-small cell lung cancer,NSCLC)的罕见类型,具有低发病率、高度恶性、强侵袭性、预后差的特点,当前无标准治疗方案。本研究拟通过收集PSC患者临床病理特征、当前诊治情况并分析预后因素,总结诊治经验,旨在提高临床对PSC的认识。方法回顾性收集2013年12月至2023年12月于北京胸科医院确诊、接受治疗且临床资料完整的39例PSC患者的人口学信息、临床病理特征、肿瘤原发灶-淋巴结-转移(tumor-node-metastasis,TNM)分期和诊疗方案资料,并完成临床预后随访。应用Kaplan-Meier法进行单因素生存分析。结果39例PSC患者年龄范围45-76岁,其中男性35例,女性4例,首诊临床表现缺乏特异性;20例患者接受手术治疗,19例患者行姑息性放化疗或对症支持治疗。患者1、5年生存率分别为61.90%、35.20%。单因素分析结果提示恶性肿瘤家族史、肿瘤部位、TNM分期、淋巴结转移、远处转移、是否手术、手术类型、治疗方案、细胞程序性死亡配体1(programmed cell death ligand 1,PD-L1)蛋白表达≥1%、间质上皮细胞转化因子(mesenchymal-epithelial transition factor,MET)通路异常与患者总生存期(overall survival,OS)有关(P<0.05);多因素分析结果显示,淋巴结转移是患者OS的独立影响因素(P=0.037)。结论PSC临床发病率低,多见于有吸烟史的老年男性。PD-L1蛋白表达≥1%及MET通路异常可提示患者不良预后,淋巴结转移是患者OS的独立危险因素。以手术为主的综合治疗是早期及局部晚期患者的主要治疗模式,靶向治疗和免疫治疗的临床应用价值有待进一步探索。

11例原发性肺黏液表皮样癌的临床病理分析

目的 探讨原发性肺黏液表皮样癌(PMEC)的临床病理及分子特征。方法 回顾性分析11例2005年1月至2021年12月经手术切除并确诊为PMEC患者的临床病理资料,并复习相关文献。结果 11例患者中,男性7例,女性4例;年龄19~58岁,中位年龄33岁;肿瘤均发生于段及段以上支气管,临床以支气管刺激症状为主。胸部CT显示10例为边界尚清晰的类圆形结节,1例显示为不规则肿块,5例伴有浅分叶。11例肿块增强扫描后均显示轻-中度的不均匀强化,肿块内有钙化者5例。1例组织学分级为高级别PMEC,10例为低级别PMEC。免疫组织化学染色结果显示,瘤细胞CK7、p63及p40阳性,TTF1、NapsinA、CK20和SMA阴性,增殖指数Ki-67约4%~28%。特殊染色示黏液细胞PAS阳性。6例患者行MAML2的FISH检测,4例患者显示MAML2基因重排阳性。11例患者均行手术治疗,其中3例术后辅助化疗。8例患者随访8~144个月,1例高级别PMEC复发。结论 PMEC是一种罕见肿瘤,其诊断需结合病理组织学特点和免疫组化,FISH检测到MAML2基因易位,主要依据术后组织病理,手术是治疗的主要方法,其预后与病理分级及临床分期相关。

SIRT5、CRIP1在肝细胞肝癌组织中的表达及临床意义

目的探讨沉默调节蛋白5(SIRT5)、富含半胱氨酸肠蛋白1(CRIP1)在肝细胞肝癌(HCC)组织中的表达及临床意义。方法选取2018年1月—2020年5月长治医学院附属和平医院肝胆外科手术切除HCC患者150例,采用免疫组化法检测HCC组织及癌旁组织中SIRT5、CRIP1表达;分析SIRT5、CRIP1表达与HCC患者临床病理参数的关系;根据HCC组织中SIRT5、CRIP1表达水平将HCC患者分为SIRT5、CRIP1阳性/阴性表达组,采用Kaplan-Meier法绘制SIRT5、CRIP1阳性/阴性表达HCC患者生存曲线;采用Cox回归分析影响HCC患者预后的因素。结果与癌旁组织比较,HCC组织SIRT5阳性表达率降低,CRIP1阳性表达率升高(χ^(2)=40.991、42.946,P均<0.001)。肿瘤单发、肿瘤直径小、中高分化程度、无脉管侵犯、TNM分期Ⅰ~Ⅱ期的HCC组织较肿瘤多发、肿瘤直径大、低分化、有脉管侵犯、TNM分期Ⅲ期的患者SIRT5阳性表达率升高、CRIP1阳性表达率降低,差异均有统计学意义(SIRT5:χ^(2)/P=5.179/0.023、6.459/0.011、5.899/0.015、7.402/0.007、5.930/0.015;CRIP1:χ^(2)/P=4.275/0.039、5.442/0.002、6.459/0.011、6.394/0.011、5.655/0.017);随访3年,150例HCC患者失访11例,3年总生存率为56.83%(79/139)。Kaplan-Meier生存曲线分析显示,SIRT5阳性表达组3年总生存率高于SIRT5阴性表达组,CRIP1阳性表达组3年总生存率低于CRIP1阴性表达组(Log-rankχ^(2)=7.552、20.942,P=0.006、<0.001)。多因素Cox回归分析显示,肿瘤数目多发、肿瘤直径≥5 cm、低分化、脉管侵犯、TNM分期Ⅲ期、CRIP1阳性为HCC患者死亡的独立危险因素[OR(95%CI)=2.685(1.031~6.999)、2.252(1.143~4.439)、4.181(1.735~10.076)、3.945(1.653~9.419)、3.485(1.492~8.141)、4.540(1.641~12.562),P均<0.05],SIRT5阳性为独立保护因素[OR(95%CI)=0.207(0.085~0.506),P<0.01]。结论HCC组织SIRT5低表达和CRIP1高表达,与肿瘤数目、肿瘤直径、分化程度、脉管侵犯、TNM分期和预后有关。

基于生物信息学分析MBD1在肝细胞癌中的表达及临床意义

目的:通过生信在线数据库分析MBD1在肝细胞癌(LIHC)中的表达及临床意义。方法:通过TIMER2.0、UALCAN、HPA、LinkedOmics数据库分析LIHC和正常肝脏组织中MBD1基因的表达水平及与患者预后的关系,并分析共表达基因和对KEGG信号通路进行富集分析。结果:MBD1在LIHC(371例)中的表达高于正常组织(50例);随着临床分期的升高,MBD1表达呈上升趋势;并且MBD1在TP53突变中表达水平较高(P<0.05)。生存分析提示,MBD1高表达的LIHC患者生存率显著降低(P<0.05)。共表达分析显示,共有6196个基因与MBD1表达呈显著正相关(P<0.05),正相关性最高的基因为PIAS2,相关系数为0.589;1946个基因与MBD1表达呈显著负相关(P<0.05),负相关性最高的是HEBP2,相关系数是-0.328。KEGG结果表明,MBD1可能与细胞周期、泛素介导的蛋白水解、核糖核酸转运、病毒性致癌等信号通路相关。结论:LIHC组织中MBD1表达增高,MBD1表达升高的LIHC患者预后较差,其可能成为LIHC治疗的新靶点。

BAIAP2L2在肝癌中的表达及与预后的关系

目的从生物信息学角度分析脑组织特异性血管生成抑制因子1关联蛋白2同类基因2(BAIAP2L2)在肝癌(LIHC)中的表达模式与预后关系、及其潜在的作用机制,并在临床病例中探讨其在LIHC中的表达与临床特征的相关性。方法在TCGA、GEPIA、GEO和TIMER数据库分析BAIAP2L2在泛癌组织和正常组织的差异表达情况,通过单因素和多因素回归分析BAIAP2L2的表达与预后的关系,采用Spearman分析法评估BAIAP2L2表达与肿瘤的基因组不稳定性的相关性;通过ssGSEA算法和KEGG富集分析与BAIAP2L2表达相关的信号通路。在临床病例中,采用免疫组化方法检测BAIAP2L2在55例LIHC组织、癌旁组织和10例正常肝组织的表达,分析其表达与病理特征、预后的相关性。结果BAIAP2L2在泛癌中普遍高表达,与相应癌旁组织、正常组织的表达有差异,与肾上腺皮质癌(ACC)、低级别胶质瘤(LGG)、间皮瘤(MESO)、前列腺癌(PRAD)、黑色素瘤(SKCM)、子宫内膜癌(UCEC)、葡萄膜黑色素瘤(UVM)等7种肿瘤的不良预后显著相关。BAIAP2L2的表达水平与食管癌(ESCA)、胰腺癌(PAAD)、UCEC的肿瘤突变负荷(TMB)正相关(P<0.05);与胆管癌(CHOL)、弥漫性大B细胞淋巴瘤(DLBC)、UVM和LGG的微卫星含量(MSI)正相关(P<0.05),与结直肠癌(READ)的MSI负相关(P<0.05)。BAIAP2L2主要参与了LIHC中16条信号通路调控,与鞘糖脂生物合成/新乳糖合成、G_(2)/M期检查点、肿瘤增殖、鞘脂代谢和糖胺聚糖生物合成硫酸角蛋白等通路正相关,与脂肪酸降解、初级胆汁酸生物合成、β-丙氨酸代谢、生物素代谢、丁酸代谢、赖氨酸降解、D-精氨酸/D-鸟氨酸的代谢、硒化合物代谢、缬氨酸/亮氨酸/异亮氨酸的降解、色氨酸代谢和咖啡因代谢等通路负相关。临床病例资料显示,LIHC组织BAIAP2L2的表达明显高于癌旁组织(P<0.0001)和正常肝组织(P=0.0036),与LIHC的肿瘤数目(P=0.038)、直径(P=0.0101)和分化程度(P=0.0314)相关;BAIAP2L2高表达组的术后总生存期低于低表达组(P=0.0182);单因素分析结果表明,BAIAP2L2表达水平与LIHC患者生存预后相关。结论BAIAP2L2通过调控TMB、MSI和多种信号通路促进肿瘤的发生、发展。BAIAP2L2在LIHC表达水平显著高于对应的癌旁组织和正常肝组织,与肿瘤数目、直径和分化程度密切相关,是促进肿瘤进展和导致不良预后的重要因素。

肝细胞癌患者癌组织中CRIP1、STUB1表达及临床预后意义

目的探讨肝细胞癌患者癌组织中富含半胱氨酸肠蛋白1(CRIP1)、STIP1同源性和包含U-box蛋白1(STUB1)表达及临床预后意义。方法选取2018年2月至2020年2月该院诊治的112例肝细胞癌患者作为研究对象。免疫组化法检测肝细胞癌患者癌组织和癌旁组织中CRIP1、STUB1表达。分析肝细胞癌患者癌组织CRIP1、STUB1表达与其临床病理特征的关系。Kaplan-Meier生存分析癌组织CRIP1、STUB1表达对肝细胞癌患者预后的影响。COX回归分析影响肝细胞癌预后的因素。结果肝细胞癌患者癌组织中CRIP1阳性率为62.50%(70/112),明显高于癌旁组织[7.14%(8/112)],差异有统计学意义(χ^(2)=76.652,P<0.05)。肝细胞癌患者癌组织中STUB1阳性率为26.23%(32/112),明显低于癌旁组织[82.14%(92/112)],差异有统计学意义(χ^(2)=73.284,P<0.05)。癌组织中CRIP1与STUB1表达呈负相关(r=-0.678,P<0.001)。不同肿瘤TNM分期、组织学分级及肿瘤最大径的肝细胞癌患者癌组织中CRIP1、STUB1阳性率比较,差异有统计学意义(P<0.05)。CRIP1阳性组3年累积生存率明显低于CRIP1阴性组,差异有统计学意义(Log-rankχ^(2)=29.601,P<0.001)。STUB1阴性组3年累积生存率明显低于STUB1阳性组,差异有统计学意义(Log-rankχ^(2)=13.590,P<0.001)。肿瘤TNM分期Ⅱ~Ⅲ期、组织学分级Ⅲ级、肿瘤最大径>5 cm、CRIP1阳性、STUB1阴性是影响肝细胞癌患者预后的独立危险因素。结论肝细胞癌患者癌组织中CRIP1表达上调,STUB1表达下调,临床上可根据肝细胞癌患者癌组织中CRIP1、STUB1表达情况对患者预后进行评估。

子宫内膜癌组织中lncRNA HOXA-AS2、FOXD2-AS1、CRNDE的表达与患者临床病理特征及预后的关系

目的探讨子宫内膜癌组织中长链非编码RNA HOXA-AS2(lncRNA HOXA-AS2)、长链非编码RNA FOXD2-AS1(lncRNA FOXD2-AS1)、长链非编码RNA CRNDE(lncRNA CRNDE)的表达与患者临床病理特征及预后的关系。方法收集2017年10月至2020年2月于该院住院手术的119例子宫内膜癌患者术中切除的子宫内膜癌的癌组织及癌旁组织标本。回顾性分析组织中HOXA-AS2、FOXD2-AS1、CRNDE相对表达水平,以及三者表达与患者临床病理特征、3年生存率的关系。结果子宫内膜癌患者癌组织HOXA-AS2、FOXD2-AS1、CRNDE相对表达水平均高于癌旁组织,差异有统计学意义(P<0.05)。子宫内膜癌患者癌组织HOXA-AS2、FOXD2-AS1、CRNDE相对表达水平两两之间均呈正相关(r_(HOXA-AS2 vs.FOXD2-AS1)=0.384,P=0.001;r_(HOXA-AS2 vs.CRNDE)=0.576,P<0.001;r_(FOXD2-AS1 vs.CRNDE)=0.326,P=0.003)。HOXA-AS2、FOXD2-AS1、CRNDE高表达组中国际妇产科学联合会分期为Ⅲ+Ⅳ期、发生淋巴结转移、浸润深度为深层、分化程度为低分化的患者所占比例高于低表达组,差异有统计学意义(P<0.05)。子宫内膜癌患者癌组织HOXA-AS2低表达组3年生存率(52/60,86.67%)高于子宫内膜癌患者癌组织HOXA-AS2高表达组(40/59,67.79%),差异有统计学意义(χ^(2)=6.039,P<0.05);子宫内膜癌患者癌组织FOXD2-AS1低表达组3年生存率(53/59,89.83%)高于子宫内膜癌患者癌组织FOXD2-AS1高表达组(39/60,65.00%),差异有统计学意义(χ^(2)=10.456,P<0.05);子宫内膜癌患者癌组织CRNDE低表达组3年生存率(51/60,85.00%)高于子宫内膜癌患者癌组织CRNDE高表达组(41/59,69.49%),差异有统计学意义(χ^(2)=4.079,P<0.05)。HOXA-AS2、FOXD2-AS1、CRNDE是子宫内膜癌患者死亡的危险因素(P<0.05)。结论子宫内膜癌的癌组织HOXA-AS2、FOXD2-AS1、CRNDE的表达与患者临床病理特征及预后密切相关。