Exploration of gene expression profiles and immune microenvironment between high and low tumor mutation burden groups in prostate cancer

BackgroundTumor mutation burden (TMB) has been established as a biomarker for response to immune therapy and prognosis in various cancers. However, the association between TMB and prognosis of prostate cancer (PCa) remains unclear. This study aimed to investigate the impact of TMB in biochemical recurrence (BCR) and the immune microenvironment in high and low TMB groups.MethodsMutation data, gene expression, clinicopathological information were downloaded from The Cancer Genome Atlas (TCGA). Mutation types and TMB values were identified. All samples were divided into high and low TMB groups with median TMB value as the cutoff point. The BCR-free survival rates, Differentially expressed genes (DEGs) and immune cells infiltrations in different TMB groups were identified.ResultsThe most common variant type and SNV were single nucleotide polymorphism and C > T. respectively. High TMB level was significantly associated with older age, positive lymph node, higher International Society of Urological Pathology (ISUP) grade, advanced stage and poor BCR-free survival. 132 DEGs were identified and involved in receptor ligand activity and hormone activity. High expression of six core genes UBE2C, PLK1, CDC20, BUB1, CDK1 and HJURP were associated with worse BCR-free survival. The analysis of immune cells infiltration revealed that the amount of activated CD4⁺ memory T cells was significantly different in high and low TMB groups.ConclusionsThe current study comprehensively described the summary of mutation and TMB related DEGs in PCa. TMB was associated with BCR-free survival and the infiltration of activated CD4⁺ memory T cells in the immune microenvironment.     

TGFB2 serves as a link between epithelial-mesenchymal transition and tumor mutation burden in gastric cancer

Immune checkpoint blockade (ICB) has been a major breakthrough in various cancers including gastric cancer (GC), yet the clinical outcomes remain poor. Currently, epithelial-mesenchymal transition (EMT) has been reported to be associated with tumor mutational burden (TMB), which can cause lack of response to ICB. However, the underlying mechanism remains unknown. Members of the transforming growth factor β (TGFB) family are regarded as the main mediators of EMT, yet how TGFB2 drives EMT in GC is not fully understood. In this study, we found that overexpression of TGFB2 was correlated with poor prognosis in TGCA-STAD and four GEO GC datasets. Gene set enrichment analysis revealed that the EMT pathway was significantly enriched in the high TGFB2 expression group, whilst the TMB-related pathways including mismatch repair, base excision repair, and DNA replication were strongly enriched in the low expression group. Furthermore, EMT score analysis, WGCNA and functional analysis showed that TGFB2 was co-expressed with neurite-related pathways that might drive EMT. Also, CIBERSORT analysis revealed that tumor-infiltrating immune cells like T follicular helper cells might participate in the process of TGFB2 affecting TMB levels in GC. Moreover, in other various cancers, TGFB2 was also negatively correlated with TMB levels as well as ICB response. Overall, these results revealed that TGFB2 could play a vital role in linking EMT and TMB in GC, suggesting that TGFB2 may be a predictive therapeutic target for GC.     

影响中青年分化型甲状腺癌患者预后因素的临床分析

目的探讨影响中青年分化型甲状腺癌者的预后因素。方法对治疗中青年全部分化型甲状腺癌患者的资料进行单因素和多因素分析。结论181例中青年分化型甲状腺癌的10年生存率为93·6%。单因素分析显示影响分化型甲状腺癌预后的因素有年龄、肿瘤大小、T分期、远处转移、治疗方式和临床病理分期(P<0·05),性别、病理类型、淋巴结转移对预后无显著性影响(P>0·05)。多因素分析表明远处转移是影响中青年分化型甲状腺癌预后的独立因素。结论年龄、肿瘤大小、T分期、远处转移和临床病理分期是影响中青年分化型甲状腺癌预后的主要因素,其中远处转移为其独立的预后因素。有远处转移的患者,行全或近全甲状腺切除术,术后行131I内照射治疗可能有利于提高其生存率。     

BRAF V600E基因突变与甲状腺乳头状癌远处转移及预后的关系

目的 研究BRAF V600E基因突变能否成为乳头状甲状腺癌（PTC）预后相关分子标志物,从而更有利于PTC的个体化治疗。方法 收集远处转移的高分化乳头状甲状腺癌患者的肿瘤组织标本共30例,运用扩增受阻突变系统（ARMS）法进行BRAF基因检测。结果 BRAF基因突变率为36.67%（11/30）,均为V600E突变;BRAF V600E基因突变与患者性别、有无淋巴结转移、远处转移情况、肿瘤病理类型及大小均无明显相关性（P>0.05）,而与患者年龄（≥45岁）显著相关（P=0.025）;BRAF突变型患者的无进展生存时间（PFS）更长（P=0.05）。结论 BRAF突变型远处转移高分化乳头状甲状腺癌患者可能预后更好。     

常规放疗治疗鼻咽癌中肿瘤退缩速度对患者预后的影响

目的 探究鼻咽癌患者行常规放疗时,其肿瘤退缩速度对预后效果的影响.方法 选择76例鼻咽癌患者,为其实施常规放疗治疗.放疗完成后,对患者的生存情况实施随访调查.比较不同退缩速度的患者在预后效果方面的差异.结果 76例患者中,快速退缩、缓慢退缩、肿瘤残留患者的5年总生存率分别为63.64％(7/11)、76.32％(29/38)、48.15％(13/27).快速退缩者5年无病生存及无远处转移生存率分别为54.55％、72.73％,缓慢退缩者为73.68％、81.58％,肿瘤残留者分别为33.33％、51.85％.结论 鼻咽癌患者行常规放疗时,肿瘤缓慢退缩、快速退缩、残留者的生存率逐次递减.     

简化的功能性颈部淋巴结清除术治疗高危甲状腺乳头状癌的临床效果

目的探讨简化的功能性颈部淋巴结清除术治疗高危甲状腺乳头状癌的临床效果。方法对1994年2月-2013年5月收治的高危甲状腺乳头状癌患者80例手术治疗的临床资料进行回顾性分析,其中1994年2月-2011年10月施行功能性颈部淋巴结清扫术50例为FND组,2011年11月-2013年5月施行简化的功能性颈部淋巴结清除术30例为SFND组。术后坚持终生服用甲状腺素片,伴有腺体外浸润的6例给予131I内照射治疗。结果施行患侧腺叶全切除＋峡部切除＋对侧次全切除术71例,双侧甲状腺全切除9例。手术近期并发症共8例（10%）,其中声音嘶哑、乳糜漏、症状性低钙血症发生率,FND组分别为4.0%（2/50）、4.0%（2/50）和2.0%（1/50）,SFND组均为3.3%（1/30）,两组比较差异无统计学意义（P〉0.05）。以3个月-1年为随访期限记录手术远期并发症,FND组与SFND组患侧颈、肩及上肢感觉异常发生率分别为16.0%（8/50）和0,活动障碍发生率分别为14.0%（7/50）和0,两组比较差异有统计学意义（P〈0.05）。结论规范的手术治疗是改善甲状腺乳头状癌患者预后的关键因素,SFND用于高危甲状腺乳头状癌的治疗,有助于保护患侧颈、肩及上肢感觉和运动功能,减少癌复发和转移。     

A robust signature associated with patient prognosis and tumor immune microenvironment based on immune-related genes in lung squamous cell carcinoma

BackgroundLung squamous cell carcinoma (LUSC) is one common type of lung cancer. Immune-related genes (IRGs) are closely associated with cancer prognosis. This study aims to screen the key genes associated with LUSC and establish an immune-related prognostic model.MethodsBased on the Cancer Genome Atlas (TCGA) database, we screened the differentially expressed genes (DEGs) between LUSC and normal samples. Intersecting the DEGs with the immune-related genes (IRGs), we obtained the differentially expressed IRGs (DEIRGs). Univariate as well as multivariate Cox regression analyses were performed to identify the survival-associated IRGs and establish an immune-related prognostic model. The relationship between the prognostic model and tumor-infiltrating immune cells was analyzed by TIMER and CIBERSORT.ResultsA total of 229 DEIRGs were screened, and 14 IRGs associated with survival were identified using univariate Cox analysis. Among the 14 IRGs, six genes were selected out using Lasso and multivariate Cox analyses, and they were used to build the prognostic model. Further analysis indicated that overall survival (OS) of high-risk groups was lower than that of low-risk groups. High risk score was independently related to worse OS. Moreover, the risk score was positively correlated with several immune infiltration cells. Finally, the efficacy of the prognostic model was validated by another independent cohort GSE73403.ConclusionThe DEIRGs described in the study may have the potential to be the prognostic molecular markers for LUSC. In addition, the risk score model could predict the OS and provides more information for the immunotherapy of patients with LUSC.     

分化型甲状腺癌患者术后应用甲状腺素及停药对心血管的影响

目的探讨分化型甲状腺癌患者术后左旋甲状腺素的应用和撤退心血管的影响。方法用化学发光法测定60例分化型甲状腺癌患者应用左旋甲状腺素形成TSH抑制(访视1)、停药后1周(访视2)、3周(访视3)及60例甲状腺功能正常的对照组血清FT3、FT4及TSH水平并查心脏彩超,动态血压监测。结果 DTC患者访视1、2时,TSH低于正常;访视3时,TSH明显高于正常。访视1、3和访视2相比均有夜间血压升高,"非杓型者"的比例明显增加。DTC患者访视3心率及心输出量明显降低,舒张功能明显减退。结论 DTC患者术后应用甲状腺素或停药对心血管均有不良影响。     

血管生长刺激因子在肝癌中的表达及肿瘤组织微血管密度和预后的关系

目的 :研究临床指标、血管生成刺激因子、组织微血管密度与患者预后的关系。方法 :用免疫组化的方法分别检测71例肝癌组织中VEGF、PCNA(增殖细胞核抗原 )、EGFR ,bFGF、PD -ECGF的表达 ,利用CD34单克隆抗体检测肝癌组织的新生血管 ,400倍光学显微镜下计算每个视野新生血管密度。结果 :(1)免疫组化表达 :71例肝癌组织中VEGF,PD -ECGF ,EGFR,bFGF,PCNA的阳性表达率分别为 :60.4 %、73.2 %、54.9%、20.1%、90 % ;(2)微血管密度 (MVD)表达 :根据MVD中位值分组 (血管数≤40为1,41～79为2 ,>80为3) ,(以中位值分组 ,就只能分为2组 )与MVD明显相关有VEGF(P=0.003) ,PD -ECGF(P=0.001) ,EGFR(P=0.004) ,MVD与bFGF和PCNA的表达无关 ;(3)肝癌患者的癌组织中的VEGF、微血管密度和有无微血管癌栓与患者的术后复发有关。多因素分析显示微血管癌栓、VEGF和肿瘤组织微血管密度影响患者的无瘤生存时间。结论 :肝癌组织中的VEGF、微血管密度和有无微小癌栓影响患者的无瘤生存期 ,可作为提示手术患者预后的指标。