Ferroptosis biomarkers predict tumor mutation burden's impact on prognosis in HER2-positive breast cancer

BACKGROUND Ferroptosis has recently been associated with multiple degenerative diseases.Ferroptosis induction in cancer cells is a feasible method for treating neoplastic diseases.However,the association of iron proliferation-related genes with prognosis in HER2+breast cancer(BC)patients is unclear.AIM To identify and evaluate fresh ferroptosis-related biomarkers for HER2+BC.METHODS First,we obtained the mRNA expression profiles and clinical information of HER2+BC patients from the TCGA and METABRIC public databases.A four gene prediction model comprising PROM2,SLC7A11,FANCD2,and FH was subsequently developed in the TCGA cohort and confirmed in the METABRIC cohort.Patients were stratified into high-risk and low-risk groups based on their median risk score,an independent predictor of overall survival(OS).Based on these findings,immune infiltration,mutations,and medication sensitivity were analyzed in various risk groupings.Additionally,we assessed patient prognosis by combining the tumor mutation burden(TMB)with risk score.Finally,we evaluated the expression of critical genes by analyzing single-cell RNA sequencing(scRNA-seq)data from malignant vs normal epithelial cells.RESULTS We found that the higher the risk score was,the worse the prognosis was(P<0.05).We also found that the immune cell infiltration,mutation,and drug sensitivity were different between the different risk groups.The highrisk subgroup was associated with lower immune scores and high TMB.Moreover,we found that the combination of the TMB and risk score could stratify patients into three groups with distinct prognoses.HRisk-HTMB patients had the worst prognosis,whereas LRisk-LTMB patients had the best prognosis(P<0.0001).Analysis of the scRNAseq data showed that PROM2,SLC7A11,and FANCD2 were significantly differentially expressed,whereas FH was not,suggesting that these genes are expressed mainly in cancer epithelial cells(P<0.01).CONCLUSION Our model helps guide the prognosis of HER2+breast cancer patients,and its combination with the TMB can aid in more accurate assessment of patient prognosis and provide new ideas for further diagnosis and treatment.

High baseline tumor burden-associated macrophages promote an immunosuppressive microenvironment and reduce the efficacy of immune checkpoint inhibitors through the IGFBP2-STAT3-PD-L1 pathway

Background:Several clinical studies have uncovered a negative correlation between baseline tumor burden and the efficacy of immune checkpoint inhibitor(ICI)treatment.This study aimed to uncover the specific mechanisms underlying the difference in sensitivity to ICI treatment between tumors with high(HTB)and low(LTB)tumor burden.Methods:For in vivo studies,several mouse models of subcutaneous tumors were established,and transcriptome sequencing,immunohistochemistry,and flow cytometry assays were used to detect the immune status in these subcutaneous tumors.For in vitro experiments,co-culture models,cytokine antibody arrays,western blotting,flow cytometry,and enzyme-linked immunosorbent assays were used to explore the underlying molecular mechanisms Results:We found that MC38 or B16 subcutaneous tumors from the HTB group did not show any response to anti-programmed cell death protein-1(PD-1)therapy.Through flow cytometry assays,we found that the infiltration with CD8^(+)T cellswas significantly decreasedwhereasM2-like macrophageswere enriched in subcutaneous tumors of HTB groups compared with those of LTB group.These changes were not affected by the initial number of injected tumor cells or tumor age,nor could they be reversed by surgical tumor reduction.Intraperitoneal colony-stimulating factor 1 receptor(CSF-1R)inhibitor PLX3397 injection at different time points of tumor growth only had an effect when administered in the early tumor stage to maintain the“heat”of the tumor microenvironment during the process of tumor growth,thereby achieving a response to ICI treatment when the tumor grew to a large size.Mechanistically,we found that insulin-like growth factor binding protein 2(IGFBP2)expression levelswere significantly elevated in HTB tumor tissues.IGFBP2 promoted the programmed death-ligand 1(PD-L1)expression in M2-like macrophages by activating signal transducer and activator of transcription 3(STAT3),and PD-L1^(+)M2-likemacrophages exerted an immunosuppressive effect by inhibiting the proliferation and activation of CD8^(+)T cells in a PD-L1-dependent fashion.Conclusions:This study suggested that the low efficacy of ICI treatment in HTB tumors is mainly attributed to the intratumoral accumulation of PD-L1^(+)M2-like macrophages via the IGFBP2-STAT3-PD-L1 signaling pathway and their substantial inhibitory effects on T cell proliferation and activation.

The correlation of miRNA expression and tumor mutational burden in uterine corpus endometrial carcinoma

Background:The relationship between microRNA(miRNA)expression patterns and tumor mutation burden(TMB)in uterine corpus endometrial carcinoma(UCEC)was investigated in this study.Methods:The UCEC dataset from The Cancer Genome Atlas(TCGA)database was used to identify the miRNAs that differ in expression between high TMB and low TMB sample sets.The total sample sets were divided into a training set and a test set.TMB levels were predicted using miRNA-based signature classifiers developed by Lasso Cox regression.Test sets were used to validate the classifier.This study investigated the relationship between a miRNA-based signature classifier and three immune checkpoint molecules(programmed cell death protein 1[PD-1],programmed cell death ligand 1[PD-L1],cytotoxic T lymphocyte-associated antigen 4[CTLA-4]).For the miRNA-based signature classifier,functional enrichment analysis was performed on the miRNAs.An analysis of the relationship between PD-1,PD-L1,and CTLA-4 immune checkpoint genes was carried out using the miRNA-based signature classifier.Results:We identified 27 differentially expressed miRNAs in miRNA-base signature.For predicting the TMB level,27-miRNA-based signature classifiers had accuracies of 0.8689 in the training cohort,0.8276 in the test cohort,and 0.8524 in the total cohort.The correlation between the miRNA-based signature classifier and PD-1 was negative,while the correlation between PD-L1 and CTLA4 was positive.Based on the miRNA profiling described above,we validated the expression levels of 9 miRNAs in clinical samples by quantitative reverse transcription PCR(qRT-PCR).Four of them were highly expressed and many cancer-related and immune-associated biological processes were linked to these 27 miRNAs.Thus,the developed miRNA-based signature classifier was correlated with TMB levels that could also predict TMB levels in UCEC samples.Conclusion:In this study,we investigated the relationship between a miRNAbased signature classifier and TMB levels in Uterine Corpus Endometrial Carcinoma.Further,this is the first study to confirm their relationship in clinical samples,which may provide more evidence support for immunotherapy of endometrial cancer.

The size of cell-free mitochondrial DNA in blood is inversely correlated with tumor burden in cancer patients

Circulating cell-free DNAs(cfDNAs)are fragmented DNA molecules released into the blood by cells.Previous studies have suggested that mitochondria-originated cfDNA fragments(mt-cfDNAs)in cancer patients are more fragmented than those from healthy controls.However,it is still unknown where these short mtcfDNAs originate,and whether the length of mt-cfDNAs can be correlated with tumor burden and cancer progression.In this study,we first performed whole-genome sequencing analysis(WGS)of cfDNAs from a human tumor cell line-xenotransplantation mouse model and found that mt-cfDNAs released from transplanted tumor cells were shorter than the mouse counterpart.We next analyzed blood cfDNA samples from hepatocellular carcinoma and prostate cancer patients and found that mt-cfDNA lengths were inversely related to tumor size as well as the concentration of circulating tumor DNA.Our study suggested that monitoring the size of mt-cfDNAs in cancer patients would be a useful way to estimate tumor burden and cancer progression.

Mining The Cancer Genome Atlas database for tumor mutation burden and its clinical implications in gastric cancer

BACKGROUND Tumor mutational burden(TMB)is an important independent biomarker for the response to immunotherapy in multiple cancers.However,the clinical implications of TMB in gastric cancer(GC)have not been fully elucidated.AIM To explore the landscape of mutation profiles and determine the correlation between TMB and microRNA(miRNA)expression in GC.METHODS Genomic,transcriptomic,and clinical data from The Cancer Genome Atlas were used to obtain mutational profiles and investigate the statistical correlation between mutational burden and the overall survival of GC patients.The difference in immune infiltration between high-and low-TMB subgroups was evaluated by Wilcoxon rank-sum test.Furthermore,miRNAs differentially expressed between the high-and low-TMB subgroups were identified and the least absolute shrinkage and selection operator method was employed to construct a miRNA-based signature for TMB prediction.The biological functions of the predictive miRNAs were identified with DIANA-miRPath v3.0.RESULTS C>T single nucleotide mutations exhibited the highest mutation incidence,and the top three mutated genes were TTN,TP53,and MUC16 in GC.High TMB values(top 20%)were markedly correlated with better survival outcome,and multivariable regression analysis indicated that TMB remained prognostic independent of TNM stage,histological grade,age,and gender.Different TMB levels exhibited different immune infiltration patterns.Significant differences between the high-and low-TMB subgroups were observed in the infiltration of CD8+T cells,M1 macrophages,regulatory T cells,and CD4+T cells.In addition,we developed a miRNA-based signature using 23 differentially expressed miRNAs to predict TMB values of GC patients.The predictive performance of the signature was confirmed in the testing and the whole set.Receiver operating characteristic curve analysis demonstrated the optimal performance of the signature.Finally,enrichment analysis demonstrated that the set of miRNAs was significantly enriched in many key cancer and immune-related pathways.

High tumor mutation burden indicates a poor prognosis in patients with intrahepatic cholangiocarcinoma

BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is malignancies of the biliary duct system and constitutes approximately 10%-20%of all primary liver cancers.Tumor mutation burden(TMB)is a useful biomarker across many cancer types for the identification of patients who will benefit from immunotherapy.Despite the role of TMB in calculating the effectiveness and prognosis of immune checkpoint inhibitors has been confirmed in multiple human cancer types,the prognostic value of TMB in ICC patients is rare investigated.AIM To investigate the prognostic value of TMB in patients with ICC.METHODS Data of 412 patients with ICC were included in the study.TMB was calculated as the total number of somatic non-silent protein-coding mutations divided by the coding region.The Kaplan-Meier method was used to analyze overall survival(OS),and relapse free survival(RFS).The cut-off value of TMB was determined by time-dependent receiver operating characteristic(ROC)curve.Cox regression was performed for multivariable analysis of OS.The nomogram and calibration curve were analyzed to construct and evaluate the prognostic model.RESULTS In the analysis of the time-dependent ROC curve,we defined 3.1 mut/Mb as the cut-off value of TMB.The Kaplan-Meier plot revealed that patients with high TMB had poor OS(HR=1.47,P=0.002)and RFS(HR=1.42,P=0.035).Cox regression analysis also demonstrated that TMB was an independent risk predictor for ICC(HR=1.43,P=0.0240).Furthermore,independent prognostic factors of ICC included CA19-9(HR=1.78,P=0.0005),chronic viral hepatitis(HR=1.72,P=0.0468),tumor resection(HR=2.58,P<0.0001)and disease progression(metastatic disease vs.solitary liver tumor;HR=2.55,P=0.0002).The nomogram and calibration curve also indicated the effectiveness of the constructed prognostic model.CONCLUSION TMB was an independent prognostic biomarker in patients with ICC.Moreover,patients with ICC with high TMB had poor OS and RFS as compared to those with low TMB.

Computational exploration of the significance of COPS6 in cancer:Functional and clinical relevance across tumor types

BACKGROUND The COP9 signalosome subunit 6(COPS6)has been implicated in cancer progression,while its precise role in most types of cancer remains elusive.AIM To investigate the functional and clinical relevance of COPS6 across various tumor types using publicly available databases.METHODS We used R software and online analysis databases to analyze the differential expression,prognosis,mutation and related functions of COPS6 in pan-cancer.RESULTS Differential expression analysis and survival analysis demonstrated that COPS6 was highly expressed and associated with high-risk profiles in the majority of cancer types.Possible associations between COPS6 expression level and prognostic outcomes were found using data from public databases.Mutational analysis revealed that missense mutations were the predominant type of COPS6 mutation.Additionally,positive correlations were identified between COPS6 expression level and tumor mutational burden and microsatellite instability in most types of cancer.Immune infiltration analysis demonstrated a negative correlation between COPS6 expression level and CD8+T cell infiltration in certain types of cancer.The correlation between COPS6 expression level and cancerassociated fibroblast infiltration exhibited heterogeneity,in which a positive correlation was found in head and neck squamous cell carcinoma and tenosynovial giant cell tumor,and a negative correlation was identified in diffuse large B-cell lymphoma and thymoma.The correlation between COPS6 expression level and macrophage infiltration was closely related to macrophage type.Gene co-expression and enrichment analysis highlighted transcription elongation factor B polypeptide 2 and G protein pathway suppressor 1 were significantly and positively associated with COPS6 expression level.These genes were predominantly involved in processes,such as ubiquitin-mediated proteolysis and human immunodeficiency virus 1 infection.CONCLUSION In conclusion,this study systematically explored the significance of COPS6 across different tumor types,providing a solid foundation for considering COPS6 as a novel biomarker in cancer research.

妇科恶性肿瘤患者家庭照顾负荷现状调查及影响因素分析

目的:分析妇科恶性肿瘤患者家庭照顾负荷现状及影响因素。方法:采用便利抽样方法,选取2022年3月-2024年1月在本院就诊的妇科恶性肿瘤患者的照顾者进行问卷调查。使用照顾负荷问卷(CBI)评估照顾者照顾负荷水平,总分96分,0~32分为CBI较低组,33~96分为CBI较高组。采用单因素及logistic回归分析影响照顾者CBI评分可能影响因素。结果:共发放问卷297份,有效问卷290份,有效率97.6%。290例照顾者的CBI为60.36±5.55分,其中CBI≤32分110例(37.9%),≥33分180例(62.1%)。单因素及多元回归分析显示,照顾者年龄大、文化程度低、月收入低、居住在农村、每日照顾时间长、患者患病时间长、患者年住院次数多是妇科恶性肿瘤患者照顾者CBI评分升高影响因素(P<0.05)。结论:本次调查的妇科肿瘤患者CBI评分较高,照顾负荷相对较重,照顾者年龄大、文化程度低、月收入低、居住农村、每日照顾时间长,以及患者患病时间长、年住院次数多是影响照顾者CBI独立因素。提高恶性肿瘤患者社会及家庭支持,构建基于医院-社区-家庭三元联动的健康管理模式等将有助于缓解恶性肿瘤患者家庭照顾负荷,对恶性肿瘤患者的疾病治疗和康复有重要意义。

2019年广西恶性肿瘤流行情况及疾病负担分析

目的分析2019年广西恶性肿瘤流行情况与疾病负担特征,为广西恶性肿瘤防治提供参考。方法根据广西56个肿瘤登记地区上报的2019年肿瘤登记数据,计算2019年广西恶性肿瘤发病率、中国人口年龄标准化发病率(简称中标发病率)、死亡率、中国人口年龄标准化死亡率(简称中标死亡率),分析2019年广西恶性肿瘤发病和死亡情况;计算伤残调整生命年(disability adjusted life years,DALYs)、早死所致的寿命损失年(years of life lost,YLLs)等指标,评价2019年广西恶性肿瘤的疾病负担。结果2019年广西56个肿瘤登记地区报告恶性肿瘤新发病例数为71430例,粗发病率为219.87/10万,中标发病率为172.17/10万;报告恶性肿瘤死亡数为45485例,粗死亡率为140.01/10万,中标死亡率为105.25/10万。2019年广西全部恶性肿瘤合计损失的DALYs为660930.15人年,YLLs占DALYs的97.4%,DALYs率为2034.40/10万。2019年广西恶性肿瘤的发病率、死亡率及DALYs率呈现男性高于女性、城市地区高于农村地区的特点。此外,在广西5个地理区域中,恶性肿瘤发病率、死亡率及DALYs率最高的地区分别是桂北地区、桂南地区和桂西地区。2019年广西恶性肿瘤发病前10位癌种分别是肝癌、肺癌、女性乳腺癌、结直肠癌、子宫颈癌、胃癌、鼻咽癌、子宫体癌、前列腺癌和甲状腺癌,发病数占全部恶性肿瘤的75.3%;恶性肿瘤死亡前10位癌种分别是肝癌、肺癌、结直肠癌、胃癌、女性乳腺癌、子宫颈癌、鼻咽癌、食管癌、白血病和脑癌,死亡数占全部恶性肿瘤死亡的82.1%。结论2019年广西恶性肿瘤的疾病负担仍处于较高水平,具有明显的性别差异及地区差异。肝癌、肺癌、女性乳腺癌、结直肠癌、子宫颈癌以及鼻咽癌等仍是广西重点防控的恶性肿瘤。此外,甲状腺癌发病顺位上升到恶性肿瘤发病顺位第10位,应重点关注并及早采取措施加以防范。

2014-2020年重庆市九龙坡区恶性肿瘤疾病负担分析

目的分析重庆市九龙坡区恶性肿瘤疾病负担特征,为开展恶性肿瘤防治提供建议。方法收集2014-2020年重庆市九龙坡区恶性肿瘤发病死亡资料,采用SPSS19.0软件分析恶性肿瘤发病率、标化发病率(ASRIC)、死亡率、标化死亡率(ASRMC)、伤残调整寿命年(DALY)、早死所致的寿命损失年(YLL)、伤残所致寿命损失年(YLD)等指标。利用χ^(2)检验比较不同性别间发病率和死亡率。结果2014-2020年重庆市九龙坡区恶性肿瘤年均粗发病率、ASRIC分别为287.25/10万、206.24/10万,其中男性恶性肿瘤年均粗发病率、ASRIC分别为337.34/10万、228.71/10万,女性分别为238.41/10万、182.66/10万,历年恶性肿瘤年均粗发病率不同性别间比较差异均有统计学意义(P<0.05);2014-2020年重庆市九龙坡区恶性肿瘤年均粗死亡率、ASRMC分别为180.41/10万、118.72/10万,其中男性恶性肿瘤年均粗死亡率、ASRMC分别为247.70/10万、158.86/10万,女性分别为114.81/10万、78.68/10万,历年恶性肿瘤粗死亡率不同性别间比较差异均有统计学意义(P<0.05);2014-2020年重庆市九龙坡区恶性肿瘤年均YLL率、YLD率、DALY率分别为47.02‰、1.78‰、48.79‰;DALY率构成中,YLL率构成占比(96.37%)明显大于YLD率占比(3.63%)。结论2014-2020年重庆市九龙坡区恶性肿瘤的疾病负担仍较重,尤其是男性人群,YLL率是疾病负担过重的主要原因,应采取针对性措施进行管理和预防。

潜在生物标志物预测PD-1/PD-L1抑制剂治疗恶性肿瘤临床疗效的Meta分析

目的:研究可预测PD-1/PD-L1抑制剂治疗恶性肿瘤临床疗效的潜在生物标志物。方法:检索PubMed、Web of Science、CNKI、万方和维普数据库,检索时限为各数据库建库至2022年9月20日。由2名评价员独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用RevMan5.4和STATA16.0软件进行Meta分析。结果:共纳入18项研究,共计4018例患者。在随访的1年和2年内,发现高水平肿瘤突变负担(TMB)的肿瘤患者使用PD-1/PD-L1抑制剂的总生存率(OS)(P=0.003,P=0.01)和无进展生存率(PFS)(P=0.0002,P=0.04)更高。在不同的随访时间内,以1%为临界值,PD-L1表达高低作为预测PD-1/PD-L1抑制剂OS和PFS的生物标志物差异无统计学意义(P>0.05)。结论:TMB可以作为预测PD-1/PD-L1抑制剂治疗恶性肿瘤患者后2年内临床疗效的生物学指标,但其效用能否持续更长时间有待进一步研究;PD-L1单项检测目前不能成为预测应用PD-1/PD-L1抑制剂受益与否的生物学标志物。

PD-1单抗治疗一例dMMR/MSI-H/TMB-H型结肠癌伴颅内转移瘤患者临床完全缓解

一例70岁男性患者,在接受右半肠癌根治性手术1年后出现了记忆丧失和认知功能下降的症状,头颅磁共振成像检查发现脑部肿块,手术后经病理检查确诊为结肠腺癌转移。原发灶及颅内转移瘤免疫组织化学检测均提示为错配修复缺陷。原发结肠肿瘤组织基因检测证实为微卫星高度不稳定伴有高肿瘤突变负荷,肿瘤突变负荷为77.7 muts/Mb。患者结肠癌根治术和颅内转移瘤术后均接受了辅助化疗,但在颅内转移瘤切除术和化疗结束后1个月颅内转移复发。患者接受帕博利珠单抗治疗后结果颅内转移瘤消退并达到临床完全缓解。

动态对比增强磁共振成像及弥散加权成像参数与乳腺癌肿瘤突变负荷的相关性

目的探讨动态对比增强磁共振成像(DCE-MRI)及弥散加权成像(DWI)参数与乳腺癌肿瘤突变负荷(TMB)的相关性,评价DCE-MRI及DWI在乳腺癌免疫治疗中的潜在价值。方法回顾性分析山西医科大学附属运城医院暨第八临床医学院2019~2021年共100例乳腺癌患者的临床资料和术前MRI检查结果。根据TMB值的中位数(5.4/Mb),将100例患者分为TMB高表达组(TMB≥5.4/Mb,n=28)和TMB低表达组(TMB<5.4/Mb,n=72)。提取DCE-MRI及DWI的影像特征,计算表观扩散系数(ADC)和动态增强曲线类型等参数。采用高通量测序技术检测肿瘤组织中的基因突变情况,计算TMB值。分析DCE-MRI及DWI参数与TMB值之间的相关性,以及与乳腺癌病理指标[雌激素受体、孕激素受体、人表皮生长因子受体2、Ki67]之间的关系。采用单因素和多因素Logistic回归分析筛选影响TMB值的独立危险因素。结果DCE-MRI及DWI参数中,ADC值、动态增强曲线类型、峰值信号强度、时间-信号强度曲线斜率等与TMB值呈负相关关系(P<0.05),而峰时、时间-信号强度曲线下面积等与TMB值呈正相关关系(P<0.05)。乳腺癌病理指标中,雌激素受体、孕激素受体、人表皮生长因子受体2、Ki67的表达与TMB值均无相关性(P>0.05)。多因素Logistic回归分析显示,ADC值、动态增强曲线类型和峰时是影响TMB值的独立危险因素。结论DCEMRI及DWI参数与乳腺癌TMB值存在显著相关性,可作为评估乳腺癌免疫治疗效果的辅助手段。

双硫死亡相关lncRNA建立胰腺癌新的预后特征并预测免疫治疗反应

目的筛选与双硫死亡相关的长链非编码RNA(lncRNA),研究其在胰腺癌中的免疫景观,为临床实践提供更有效的指导。方法从癌症基因组图谱(TCGA)数据库中获取胰腺癌组织和癌旁正常组织样本,基于Cox回归和LASSO回归分析鉴定双硫死亡相关lncRNA。构建风险评分模型,通过综合方法验证其预测性能。构建精确的列线图,预测胰腺癌患者的预后。通过基因本体(GO)、基因集富集分析(GSEA)和免疫分析研究生物学差异。通过肿瘤突变负荷(TMB)估计免疫治疗反应。结果成功鉴定出251个双硫死亡相关lncRNA,筛选出3组lncRNA作为风险评分模型的参考。通路分析结果表明,免疫相关通路与双硫死亡相关lncRNA风险评分模型相关。风险评分与免疫细胞浸润以及ESTIMATE评分显著相关。风险评分较高的患者TMB升高,表明高风险患者表现出更好的免疫检查点阻断反应。结论本研究的发现有助于深入理解双硫死亡相关lncRNA在胰腺癌中的作用,为胰腺癌提供潜在的治疗策略。

全外显子测序揭示原发中枢神经系统淋巴瘤的基因突变特征

目的:对18例原发中枢神经系统淋巴瘤(PCNSL)患者肿瘤组织进行全外显子测序,探索PCNSL的基因突变特点。方法:收集2018年9月至2020年12月在兰州大学第二医院病理科确诊的18例免疫功能正常(无HIV及服用免疫抑制剂病史)、病理类型为弥漫大B细胞淋巴瘤的PCNSL患者肿瘤组织,进行基于高通量测序的全外显子测序,平均测序深度>100×。测序结果经数据处理及生物信息学分析,得到患者的基因突变全景及突变特征。结果:18例患者均检测到明显的体细胞突变,中位体细胞突变数目为321,以错义突变为主(约占90%),突变类型以C>T为主(占50.2%),反映了与年龄相关的突变模式;前15位高频突变基因中,PSD3、DUSP5、MAGEB16、TELO2、FMO2、TRMT13、AOC1、PIGZ、SVEP1、IP6K3、TIAM1为驱动基因。驱动基因通路富集结果显示,RTK-RAS、Wnt、NOTCH、Hippo、Cell-Cycle通路明显富集。各样本的肿瘤突变负荷在3.558 48/Mb-8.780 89/Mb之间,平均突变负荷4.953 32/Mb,与TCGA数据库中其他肿瘤的研究队列相比明显增高。结论:PCNSL频繁发生体细胞的错义突变,以点突变为主,突变类型主要为C>T。驱动基因主要参与RTK-RAS、Wnt、NOTCH、Hippo通路信号传导,表明以上通路可能与PCNSL发病机制相关。PCNSL有显著的高肿瘤突变负荷,这或许是PD-1抑制剂治疗PCNSL有效的原因之一。

基于铜死亡相关的铁死亡基因构建预测肝癌患者预后的模型

目的构建基于铜死亡相关的铁死亡基因的预后模型,评估其在肝癌患者中的预测能力,并探讨与免疫功能和肿瘤突变负荷的关系。方法使用TCGA(The Cancer Genome Atlas)数据库分析370例肝癌患者的与铜死亡相关的铁死亡基因和生存数据,并将数据集随机分为训练组和测试组。通过Lasso回归和Cox模型的构建,筛选出与铜死亡相关的铁死亡基因进行风险模型构建。进行单因素和多因素Cox回归分析来验证风险模型对肝癌预后影响的独立性,并分析风险模型与免疫功能和肿瘤突变负荷的关系。结果在多变量Cox回归数据中选择EIF2S1、G6PD、NRAS这3个与铜死亡相关的铁死亡基因,训练组中EIF2S1、G6PD、NRAS与生存期独立相关(P均<0.05),以该3个基因构建风险模型。Kaplan-Meier分析结果显示,与低风险组比较,高风险组患者的生存期较短(P<0.05),生存率较低(P<0.05)。单因素Cox回归分析显示,铜死亡相关的铁死亡基因构建的风险模型中HR为1.734,95%CI为1.494~2.034,P<0.001。多因素Cox回归分析显示,铜死亡相关的铁死亡基因构建的风险模型中HR为1.661,95%CI为1.397~1.976,P<0.001。ROC曲线分析显示,风险模型预测肝癌患者第1,3,5年生存期的曲线下面积(AUC)分别为0.760,0.663和0.636。运用该风险模型进行Kaplan-Meier生存曲线分析显示,与早期肝癌患者相比,晚期肝癌患者生存期更短(P<0.05),生存率更低(P<0.05)。在高风险组和低风险组中,TypeⅡIFN Response、Parainflammation、APC co-stimulation、CCR、Check-point和MHC classⅠ这6个免疫功能的表达存在统计学差异(P均<0.05)。高肿瘤突变负荷组的肝癌患者生存期明显低于低肿瘤突变负荷组的患者(P<0.05)。结论基于与铜死亡相关的铁死亡基因的风险模型能够有效区分肝癌患者的预后,且铜死亡相关的铁死亡基因与免疫功能和肿瘤突变负荷密切相关。

基于生物信息学分析FAM83H-AS1在乳腺癌中的表达及临床意义

目的通过生物信息学分析FAM83H-AS1在乳腺癌中的表达及其对临床治疗和预后评估的意义。方法下载癌症基因组图谱(the Cancer Genome Atlas,TCGA)数据库中多种肿瘤表达资料,采用R语言分析FAM83H-AS1在多种癌症中的表达情况。单独分析FAM83H-AS1在乳腺癌中的表达情况,并通过基于基因表达水平值的交互式分析平台(Gene Expression Profiling Interactive Analysis,GEPIA)在线数据库验证表达情况。利用TCGA数据库下载并分析生存资料,明确FAM83H-AS1表达水平与乳腺癌患者预后的关系,并利用GEPIA及Kaplan-Meier Plotter进行双重验证。同时利用TCGA临床信息分析FAM83H-AS1与临床病理分期的关系,运用R语言分析FAM83H-AS1与肿瘤微环境、免疫检测点相关基因及肿瘤突变负荷(tumor mutation burden,TMB)的相关性,并进行基因集富集分析(gene set enrichment analysis,GSEA)。结果FAM83H-AS1在多种癌症中表达异常,其中在乳腺癌中的表达显著升高,且高表达FAM83H-AS1的乳腺癌患者总生存率显著降低。此外,不同临床分期的乳腺癌患者FAM83H-AS1的表达水平不同。FAM83H-AS1与乳腺癌样本中的基质细胞评分及免疫细胞评分均呈负相关,与一些免疫检测点相关基因表达具有相关性,TMB雷达图结果提示FAM83H-AS1在乳腺癌中的表达与TMB存在正相关性,GSEA结果提示FAM83H-AS1的表达与错配修复功能呈正相关性。结论FAM83H-AS1基因在乳腺癌中高表达,与患者的不良预后、临床病理分期、肿瘤微环境及TMB均有相关性。同时FAM83H-AS1与免疫检测点相关的一些基因及错配修复基因存在相关性,以上可能为临床乳腺癌的治疗、预测预后及基因靶向药物的研制提供理论依据。

Value of metabolic parameters in distinguishing primary mediastinal lymphomas from thymic epithelial tumors

Objective:A high rate of unnecessary thymectomies has been reported.This study aimed to distinguish primary mediastinal lymphomas(PMLs)from thymic epithelial tumors(TETs)by evaluating volumetric and metabolic parameters with l8F-FDG PET/CT.Methods:A total of 136 patients who were pathologically diagnosed with TETs or PMLs were enrolled,and 18F-FDG PET/CT was performed before therapy.Volumetric parameters,including the mean SUV(SUVmean),metabolic tumor volume(MTV),total lesion glycolysis(TLG),and SUVmax,were determined and compared between the 2 subtypes.The diagnostic performance of these parameters was evaluated with receiver operating characteristic(ROC)curve analysis.Results:All parameters significantly differed between patients with PMLs and TETs.Patients with lymphomas were younger and had higher SUVmean,SUVmax,TLG,and MTV values than patients with TETs.The MTV and TLG values had similar diagnostic performance.ROC analysis indicated that the areas under the curves of the SUVmean and SUVmax values performed similarly(approximately 0.76)in differentiating patients with PMLs from TETs,and both values were better than the MTV and TLG values.When age was included with the SUVmax in differentiating TETs from PMLs,the AUC was 0.91,and the sensitivity and specificity increased to 80%and 93%,respectively.Conclusions:The SUVmax and volumetric parameters of 18F-FDG PET/CT can be used to distinguish patients with PMLs versus TETs,and thus may aid in preventing unnecessary thymectomies or other invasive operations.

原发性脑肿瘤患者自我感受负担现状及其影响因素分析

目的调查原发性脑肿瘤(PBT)患者自我感受负担(SPB)现状并分析其影响因素。方法选取2022年3月至11月在四川省南充市某三甲医院神经外科住院部的270例患者作为研究对象,进行横断面调查研究。调查工具包括一般资料调查表、卡诺夫斯基功能状态量表(KPS)和自我感受负担量表(SPBS-CP)。采用多元线性回归分析SPB的影响因素。结果最终纳入257例PBT患者,患者的SPBS-CP总分为(53.18±22.19)分。多元线性回归分析结果显示,病程>6个月、KPS评分≤70分、学历越低、医疗负担越重、照顾者为其他的患者SPBS-CP得分越高(P<0.05)。结论PBT患者SPB处于中度水平,医护人员应重点关注病程>6个月、KPS评分≤70分、学历低、医疗负担重、照顾者为其他的患者。

安罗替尼联合IP方案治疗进展/复发小细胞肺癌临床研究

目的探讨安罗替尼联合IP方案(伊立替康+顺铂)治疗进展/复发小细胞肺癌(SCLC)的临床效果及其作用机制。方法选取医院2019年6月至2021年6月收治的进展/复发SCLC患者97例,按随机数字表法分为对照组(48例)和观察组(49例),两组患者均予IP方案治疗,观察组患者加服盐酸安罗替尼胶囊。两组均以28 d为1个周期,连续治疗2个周期,随访20个月。结果观察组患者的疾病控制率显著高于对照组(P<0.05);观察组患者治疗后的血清癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)、细胞角蛋白19片段(Cyfra21-1)水平及肿瘤代谢体积(MTV)、血容量(BV)、血流量(BF)均显著低于对照组(P<0.05);观察组患者中位无进展生存期(PFS)显著长于对照组(7.5个月比5.5个月,P<0.05);两组患者的不同等级不良反应发生率、生存率均无显著差异(P>0.05)。结论安罗替尼联合IP方案治疗进展/复发SCLC,可降低患者的肿瘤负荷,延长PFS,机制可能与调节肿瘤标志物和改善血流灌注指标有关。