肺腺癌预后代谢相关基因的生物信息学分析

目的 基于代谢基因的生物信息学构建肺腺癌预后模型及验证。方法 获取癌症基因组图谱(TCGA)数据库和基因表达数据集(GEO)肺腺癌相关数据,套索(LASSO)回归构建多基因预后模型并计算风险值(RS)。单因素、多因素Cox独立预后分析,通过受试者工作特征(ROC)曲线评价模型的ROC曲线下面积(AUC)并进行生存分析。构建列线图评价模型的可行性,通过基因集富集分析(GSEA)进行代谢基因功能富集分析。肿瘤免疫评估资源(TIMER)数据库分析患者RS与免疫细胞浸润以及与免疫检查点分子表达的相关性。结果 运用TCGA数据库基于18个代谢相关基因构建肺腺癌预后模型,RS可以作为独立的预后因子。ROC曲线下面积为0.713。生存分析显示,与高风险组相比,低风险组总体生存率更高,预后模型与免疫细胞的浸润以及与免疫检查点分子的表达有关。结论 代谢相关基因肺腺癌预后模型的RS是独立预后因子,模型具有较高的预后判断价值。     

HMMR基因与肺腺癌患者预后及浸润性免疫细胞关系的生物信息学分析北大核心CSCD

目的:透明质酸介导的运动受体(HMMR)基因在多种肿瘤中异常表达,然而,其在肺腺癌(LUAD)中的预后价值及与浸润性淋巴细胞的关系未知,因此,本文着重研究HMMR在LUAD中的预后价值及与浸润性免疫细胞的关系。方法:从TCGA数据库下载LUAD组织和正常组织间的转录表达谱及相应临床信息。通过RT-PCR反应评估LUAD细胞系及正常支气管上皮细胞系HMMR的表达水平。通过临床蛋白质组学肿瘤分析联盟(CPTAC)评估HMMR蛋白表达情况。受试者工作特征(ROC)曲线用于区分LUAD组织与邻近正常组织。通过单因素及多因素Cox分析及Kaplan-Meier方法评估HMMR对患者预后的影响。通过STRING构建蛋白质-蛋白质相互作用(PPI)网络。采用R语言“ClusterProfiler”包进行功能富集分析。通过TIMER评估HMMR在不同肿瘤中的表达情况及与LUAD浸润性免疫细胞浸润丰度间的关系。结果:HMMR在肺腺癌组织及细胞系中的表达较邻近正常组织或正常支气管上皮细胞系中显著上调。HMMR表达增加与吸烟超过40年、R1或R2残留肿瘤、高T分期、淋巴结转移、远处转移和高TNM分期相关。Kaplan-Meier生存分析显示,HMMR高表达组的LUAD患者预后较低表达组患者差(41.9个月vs 59.9个月,P<0.001),各亚组分析也显示相似的结果。ROC曲线分析表明,在截断水平为2.103的情况下,HMMR区分LUAD与相邻对照的敏感性和特异性分别为98.3%和86.2%。相关分析表明,HMMR的表达水平与肿瘤浸润性免疫细胞的浸润丰度相关。结论:HMMR表达上调与LUAD预后不良和免疫浸润显著相关,可以作为LUAD预后不良的生物标志物及免疫治疗靶点。     

基于生物信息学方法分析SHCBP1基因在肺腺癌中的表达及临床意义

目的：分析SHC的SH2结构域结合蛋白1(SHCBP1)在肺腺癌（LUAD）中的表达及临床意义。方法：应用Oncomine、TIMER、UALCAN、GEPIA、Kaplan-Meier plotter、STRING数据库探索SHCBP1对LUAD进展及免疫浸润的影响。结果：LUAD组织中SHCBP1 mRNA表达显著高于正常肺组织（P<0.05）。有吸烟史、发生淋巴结转移、临床分期较晚、TP53突变的LUAD患者组织中SHCBP1 mRNA表达明显升高（P<0.05）。GEPIA和Kaplan-Meier plotter数据库进行的生存分析表明SHCBP1 mRNA高表达的LUAD患者总体生存率较低（P<0.05）。SHCBP1 mRNA与LUAD肿瘤免疫细胞浸润、免疫细胞标记物、免疫检查点表达相关。结论：SHCBP1高表达与LUAD患者的不良预后和肿瘤免疫浸润相关。     

pT1期肺腺癌间质浸润的分级及预后意义

目的 探讨TNM病理分期T1(pathologic-T1,pT1)期肺腺癌中间质浸润分级的预后意义.方法 选择具有完整临床病理及随访资料结果 的pT1期肺腺癌85例,根据间质浸润在肿瘤中的部位将每例肿瘤中间质浸润的程度分为1-3级,分析各间质浸润级别病例的临床病理特征及预后.结果 间质浸润各级别肿瘤的病例数为1级:17例(20%),2级:12例(14%),3级:56例(66%).临床病理特征:肿瘤大小及淋巴血管侵犯率除1级病例小于3级病例(P值分别为0.005及0.018)外其余各级病例间的差异无统计学意义.淋巴结转移率及病理学分期在1级和2级病例完全相同并低于3级病例(1级与3级P值分别为0.007及0.002;2级与3级P值分别为0.027及0.021).性别、年龄及吸烟史各级病例间的差异无统计学意义.预后:本组病例5年总生存率是63%.1-3级病例的5年生存率分别为100%、83.3%及46.6%,2级与3级病例间的差异有统计学意义(P=0.027),随访期间病死率1-3级病例分别为0、16.7%及42.9%,1级与3级病例间的差异有统计学意义(P=0.001),而与2级病例间的差异无统计学意义.单因素预后分析提示间质浸润分级(P=0.001)、病理学分期(P<0.001)、淋巴血管侵犯(P<0.001)及淋巴结转移(P<0.001)与预后相关.多因素预后分析提示仅病理学分期(P<0.001)为独立预后因素.结论 间质浸润分级是一个与肿瘤预后及其他预后因素均密切相关组织学分级系统,它可作为pT1期肺腺癌预后分类的标准之一.     

pT1期肺腺癌间质浸润的分级及预后意义

Objective To study the prognostic significance of grading system for stromal invasion in pathologic tumor stage Tl (pTl) adenocarcinoma of lung.Methods Eighty-five cases of surgically resected pTl lung adenocarcinoma with clinicopathologic and follow-up data were retrospectively reviewed.The degree of invasive growth was classified into three grades according to its location in the tumor.The clinicopathologic characteristics and prognostic significance were analyzed.Results Amongst the 85 cases studied,17 cases (20% ) were in grade 1,12 (14% ) in grade 2 and 56 (66% ) in grade 3.The tumor size was smaller and lymphovascular permeation was less frequently encountered in cases with grade 1 stromal invasion than in those with grade 3 (P =0.005 for tumor size and P =0.018 for occurrence of lymphovascular permeation).The rate of lymph node metastasis and pathologic staging in cases with grade 1 and grade 2 were similar and were significantly lower than those with grade 3 ( P = 0.007 for rate of lymph node metastasis in grade 1 versus grade 3 tumors,P = 0.002 for pathologic stage in grade 1 versus grade 3 tumors,P = 0.027 for rate of lymph node metastasis in grade 2 versus grade 3 tumors and P =0.021 for pathologic stage in grade 2 versus grade 3 tumors).There was no statistically significant difference with respect to age,gender and smoking history of the patients,amongst cases in different grades.The overall five-year survival rate was 63%.The five-year survival rates for cases with grade 1,grade 2 and grade 3 were 100% ,83.3% and 46.6% ,respectively.The difference between cases with grade 2 and grade 3 was statistically significant (P =0.027).The death rate during follow-up for cases with grade 1,grade 2 and grade 3 were 0,16.7% and 42.9% ,respectively.The difference between cases with grade 1 and grade 3 was statistically significant ( P - 0.001).Univariate analysis showed that grade of stromal invasion (P = 0.001),pathologic stage (P<0.001),presence of lymphovascular permeation (P < 0.001) and lymph node involvement　(P < 0.001) represented important prognostic factors.Multivariate analysis also showed that pathologic stage (P <0.001) was an independent prognostic factor.Conclusions The grading system of stromal invasion in pulmonary adenocarcinoma correlates with tumor prognosis and other prognostic factors.It represents a useful criterion in prognostic categorization of pTl adenocarcinoma of lung.     

pT1期肺腺癌间质浸润的分级及预后意义

Objective To study the prognostic significance of grading system for stromal invasion in pathologic tumor stage Tl (pTl) adenocarcinoma of lung.Methods Eighty-five cases of surgically resected pTl lung adenocarcinoma with clinicopathologic and follow-up data were retrospectively reviewed.The degree of invasive growth was classified into three grades according to its location in the tumor.The clinicopathologic characteristics and prognostic significance were analyzed.Results Amongst the 85 cases studied,17 cases (20% ) were in grade 1,12 (14% ) in grade 2 and 56 (66% ) in grade 3.The tumor size was smaller and lymphovascular permeation was less frequently encountered in cases with grade 1 stromal invasion than in those with grade 3 (P =0.005 for tumor size and P =0.018 for occurrence of lymphovascular permeation).The rate of lymph node metastasis and pathologic staging in cases with grade 1 and grade 2 were similar and were significantly lower than those with grade 3 ( P = 0.007 for rate of lymph node metastasis in grade 1 versus grade 3 tumors,P = 0.002 for pathologic stage in grade 1 versus grade 3 tumors,P = 0.027 for rate of lymph node metastasis in grade 2 versus grade 3 tumors and P =0.021 for pathologic stage in grade 2 versus grade 3 tumors).There was no statistically significant difference with respect to age,gender and smoking history of the patients,amongst cases in different grades.The overall five-year survival rate was 63%.The five-year survival rates for cases with grade 1,grade 2 and grade 3 were 100% ,83.3% and 46.6% ,respectively.The difference between cases with grade 2 and grade 3 was statistically significant (P =0.027).The death rate during follow-up for cases with grade 1,grade 2 and grade 3 were 0,16.7% and 42.9% ,respectively.The difference between cases with grade 1 and grade 3 was statistically significant ( P - 0.001).Univariate analysis showed that grade of stromal invasion (P = 0.001),pathologic stage (P<0.001),presence of lymphovascular permeation (P < 0.001) and lymph node involvement　(P < 0.001) represented important prognostic factors.Multivariate analysis also showed that pathologic stage (P <0.001) was an independent prognostic factor.Conclusions The grading system of stromal invasion in pulmonary adenocarcinoma correlates with tumor prognosis and other prognostic factors.It represents a useful criterion in prognostic categorization of pTl adenocarcinoma of lung.     

pT1期肺腺癌间质浸润的分级及预后意义

Objective To study the prognostic significance of grading system for stromal invasion in pathologic tumor stage Tl (pTl) adenocarcinoma of lung.Methods Eighty-five cases of surgically resected pTl lung adenocarcinoma with clinicopathologic and follow-up data were retrospectively reviewed.The degree of invasive growth was classified into three grades according to its location in the tumor.The clinicopathologic characteristics and prognostic significance were analyzed.Results Amongst the 85 cases studied,17 cases (20% ) were in grade 1,12 (14% ) in grade 2 and 56 (66% ) in grade 3.The tumor size was smaller and lymphovascular permeation was less frequently encountered in cases with grade 1 stromal invasion than in those with grade 3 (P =0.005 for tumor size and P =0.018 for occurrence of lymphovascular permeation).The rate of lymph node metastasis and pathologic staging in cases with grade 1 and grade 2 were similar and were significantly lower than those with grade 3 ( P = 0.007 for rate of lymph node metastasis in grade 1 versus grade 3 tumors,P = 0.002 for pathologic stage in grade 1 versus grade 3 tumors,P = 0.027 for rate of lymph node metastasis in grade 2 versus grade 3 tumors and P =0.021 for pathologic stage in grade 2 versus grade 3 tumors).There was no statistically significant difference with respect to age,gender and smoking history of the patients,amongst cases in different grades.The overall five-year survival rate was 63%.The five-year survival rates for cases with grade 1,grade 2 and grade 3 were 100% ,83.3% and 46.6% ,respectively.The difference between cases with grade 2 and grade 3 was statistically significant (P =0.027).The death rate during follow-up for cases with grade 1,grade 2 and grade 3 were 0,16.7% and 42.9% ,respectively.The difference between cases with grade 1 and grade 3 was statistically significant ( P - 0.001).Univariate analysis showed that grade of stromal invasion (P = 0.001),pathologic stage (P<0.001),presence of lymphovascular permeation (P < 0.001) and lymph node involvement　(P < 0.001) represented important prognostic factors.Multivariate analysis also showed that pathologic stage (P <0.001) was an independent prognostic factor.Conclusions The grading system of stromal invasion in pulmonary adenocarcinoma correlates with tumor prognosis and other prognostic factors.It represents a useful criterion in prognostic categorization of pTl adenocarcinoma of lung.     

pT1期肺腺癌间质浸润的分级及预后意义

Objective To study the prognostic significance of grading system for stromal invasion in pathologic tumor stage Tl (pTl) adenocarcinoma of lung.Methods Eighty-five cases of surgically resected pTl lung adenocarcinoma with clinicopathologic and follow-up data were retrospectively reviewed.The degree of invasive growth was classified into three grades according to its location in the tumor.The clinicopathologic characteristics and prognostic significance were analyzed.Results Amongst the 85 cases studied,17 cases (20% ) were in grade 1,12 (14% ) in grade 2 and 56 (66% ) in grade 3.The tumor size was smaller and lymphovascular permeation was less frequently encountered in cases with grade 1 stromal invasion than in those with grade 3 (P =0.005 for tumor size and P =0.018 for occurrence of lymphovascular permeation).The rate of lymph node metastasis and pathologic staging in cases with grade 1 and grade 2 were similar and were significantly lower than those with grade 3 ( P = 0.007 for rate of lymph node metastasis in grade 1 versus grade 3 tumors,P = 0.002 for pathologic stage in grade 1 versus grade 3 tumors,P = 0.027 for rate of lymph node metastasis in grade 2 versus grade 3 tumors and P =0.021 for pathologic stage in grade 2 versus grade 3 tumors).There was no statistically significant difference with respect to age,gender and smoking history of the patients,amongst cases in different grades.The overall five-year survival rate was 63%.The five-year survival rates for cases with grade 1,grade 2 and grade 3 were 100% ,83.3% and 46.6% ,respectively.The difference between cases with grade 2 and grade 3 was statistically significant (P =0.027).The death rate during follow-up for cases with grade 1,grade 2 and grade 3 were 0,16.7% and 42.9% ,respectively.The difference between cases with grade 1 and grade 3 was statistically significant ( P - 0.001).Univariate analysis showed that grade of stromal invasion (P = 0.001),pathologic stage (P<0.001),presence of lymphovascular permeation (P < 0.001) and lymph node involvement　(P < 0.001) represented important prognostic factors.Multivariate analysis also showed that pathologic stage (P <0.001) was an independent prognostic factor.Conclusions The grading system of stromal invasion in pulmonary adenocarcinoma correlates with tumor prognosis and other prognostic factors.It represents a useful criterion in prognostic categorization of pTl adenocarcinoma of lung.     

pT1期肺腺癌间质浸润的分级及预后意义

Objective To study the prognostic significance of grading system for stromal invasion in pathologic tumor stage Tl (pTl) adenocarcinoma of lung.Methods Eighty-five cases of surgically resected pTl lung adenocarcinoma with clinicopathologic and follow-up data were retrospectively reviewed.The degree of invasive growth was classified into three grades according to its location in the tumor.The clinicopathologic characteristics and prognostic significance were analyzed.Results Amongst the 85 cases studied,17 cases (20% ) were in grade 1,12 (14% ) in grade 2 and 56 (66% ) in grade 3.The tumor size was smaller and lymphovascular permeation was less frequently encountered in cases with grade 1 stromal invasion than in those with grade 3 (P =0.005 for tumor size and P =0.018 for occurrence of lymphovascular permeation).The rate of lymph node metastasis and pathologic staging in cases with grade 1 and grade 2 were similar and were significantly lower than those with grade 3 ( P = 0.007 for rate of lymph node metastasis in grade 1 versus grade 3 tumors,P = 0.002 for pathologic stage in grade 1 versus grade 3 tumors,P = 0.027 for rate of lymph node metastasis in grade 2 versus grade 3 tumors and P =0.021 for pathologic stage in grade 2 versus grade 3 tumors).There was no statistically significant difference with respect to age,gender and smoking history of the patients,amongst cases in different grades.The overall five-year survival rate was 63%.The five-year survival rates for cases with grade 1,grade 2 and grade 3 were 100% ,83.3% and 46.6% ,respectively.The difference between cases with grade 2 and grade 3 was statistically significant (P =0.027).The death rate during follow-up for cases with grade 1,grade 2 and grade 3 were 0,16.7% and 42.9% ,respectively.The difference between cases with grade 1 and grade 3 was statistically significant ( P - 0.001).Univariate analysis showed that grade of stromal invasion (P = 0.001),pathologic stage (P<0.001),presence of lymphovascular permeation (P < 0.001) and lymph node involvement　(P < 0.001) represented important prognostic factors.Multivariate analysis also showed that pathologic stage (P <0.001) was an independent prognostic factor.Conclusions The grading system of stromal invasion in pulmonary adenocarcinoma correlates with tumor prognosis and other prognostic factors.It represents a useful criterion in prognostic categorization of pTl adenocarcinoma of lung.     

pT1期肺腺癌间质浸润的分级及预后意义

Objective To study the prognostic significance of grading system for stromal invasion in pathologic tumor stage Tl (pTl) adenocarcinoma of lung.Methods Eighty-five cases of surgically resected pTl lung adenocarcinoma with clinicopathologic and follow-up data were retrospectively reviewed.The degree of invasive growth was classified into three grades according to its location in the tumor.The clinicopathologic characteristics and prognostic significance were analyzed.Results Amongst the 85 cases studied,17 cases (20% ) were in grade 1,12 (14% ) in grade 2 and 56 (66% ) in grade 3.The tumor size was smaller and lymphovascular permeation was less frequently encountered in cases with grade 1 stromal invasion than in those with grade 3 (P =0.005 for tumor size and P =0.018 for occurrence of lymphovascular permeation).The rate of lymph node metastasis and pathologic staging in cases with grade 1 and grade 2 were similar and were significantly lower than those with grade 3 ( P = 0.007 for rate of lymph node metastasis in grade 1 versus grade 3 tumors,P = 0.002 for pathologic stage in grade 1 versus grade 3 tumors,P = 0.027 for rate of lymph node metastasis in grade 2 versus grade 3 tumors and P =0.021 for pathologic stage in grade 2 versus grade 3 tumors).There was no statistically significant difference with respect to age,gender and smoking history of the patients,amongst cases in different grades.The overall five-year survival rate was 63%.The five-year survival rates for cases with grade 1,grade 2 and grade 3 were 100% ,83.3% and 46.6% ,respectively.The difference between cases with grade 2 and grade 3 was statistically significant (P =0.027).The death rate during follow-up for cases with grade 1,grade 2 and grade 3 were 0,16.7% and 42.9% ,respectively.The difference between cases with grade 1 and grade 3 was statistically significant ( P - 0.001).Univariate analysis showed that grade of stromal invasion (P = 0.001),pathologic stage (P<0.001),presence of lymphovascular permeation (P < 0.001) and lymph node involvement　(P < 0.001) represented important prognostic factors.Multivariate analysis also showed that pathologic stage (P <0.001) was an independent prognostic factor.Conclusions The grading system of stromal invasion in pulmonary adenocarcinoma correlates with tumor prognosis and other prognostic factors.It represents a useful criterion in prognostic categorization of pTl adenocarcinoma of lung.     

pT1期肺腺癌间质浸润的分级及预后意义

Objective To study the prognostic significance of grading system for stromal invasion in pathologic tumor stage Tl (pTl) adenocarcinoma of lung.Methods Eighty-five cases of surgically resected pTl lung adenocarcinoma with clinicopathologic and follow-up data were retrospectively reviewed.The degree of invasive growth was classified into three grades according to its location in the tumor.The clinicopathologic characteristics and prognostic significance were analyzed.Results Amongst the 85 cases studied,17 cases (20% ) were in grade 1,12 (14% ) in grade 2 and 56 (66% ) in grade 3.The tumor size was smaller and lymphovascular permeation was less frequently encountered in cases with grade 1 stromal invasion than in those with grade 3 (P =0.005 for tumor size and P =0.018 for occurrence of lymphovascular permeation).The rate of lymph node metastasis and pathologic staging in cases with grade 1 and grade 2 were similar and were significantly lower than those with grade 3 ( P = 0.007 for rate of lymph node metastasis in grade 1 versus grade 3 tumors,P = 0.002 for pathologic stage in grade 1 versus grade 3 tumors,P = 0.027 for rate of lymph node metastasis in grade 2 versus grade 3 tumors and P =0.021 for pathologic stage in grade 2 versus grade 3 tumors).There was no statistically significant difference with respect to age,gender and smoking history of the patients,amongst cases in different grades.The overall five-year survival rate was 63%.The five-year survival rates for cases with grade 1,grade 2 and grade 3 were 100% ,83.3% and 46.6% ,respectively.The difference between cases with grade 2 and grade 3 was statistically significant (P =0.027).The death rate during follow-up for cases with grade 1,grade 2 and grade 3 were 0,16.7% and 42.9% ,respectively.The difference between cases with grade 1 and grade 3 was statistically significant ( P - 0.001).Univariate analysis showed that grade of stromal invasion (P = 0.001),pathologic stage (P<0.001),presence of lymphovascular permeation (P < 0.001) and lymph node involvement　(P < 0.001) represented important prognostic factors.Multivariate analysis also showed that pathologic stage (P <0.001) was an independent prognostic factor.Conclusions The grading system of stromal invasion in pulmonary adenocarcinoma correlates with tumor prognosis and other prognostic factors.It represents a useful criterion in prognostic categorization of pTl adenocarcinoma of lung.     

pT1期肺腺癌间质浸润的分级及预后意义

Objective To study the prognostic significance of grading system for stromal invasion in pathologic tumor stage Tl (pTl) adenocarcinoma of lung.Methods Eighty-five cases of surgically resected pTl lung adenocarcinoma with clinicopathologic and follow-up data were retrospectively reviewed.The degree of invasive growth was classified into three grades according to its location in the tumor.The clinicopathologic characteristics and prognostic significance were analyzed.Results Amongst the 85 cases studied,17 cases (20% ) were in grade 1,12 (14% ) in grade 2 and 56 (66% ) in grade 3.The tumor size was smaller and lymphovascular permeation was less frequently encountered in cases with grade 1 stromal invasion than in those with grade 3 (P =0.005 for tumor size and P =0.018 for occurrence of lymphovascular permeation).The rate of lymph node metastasis and pathologic staging in cases with grade 1 and grade 2 were similar and were significantly lower than those with grade 3 ( P = 0.007 for rate of lymph node metastasis in grade 1 versus grade 3 tumors,P = 0.002 for pathologic stage in grade 1 versus grade 3 tumors,P = 0.027 for rate of lymph node metastasis in grade 2 versus grade 3 tumors and P =0.021 for pathologic stage in grade 2 versus grade 3 tumors).There was no statistically significant difference with respect to age,gender and smoking history of the patients,amongst cases in different grades.The overall five-year survival rate was 63%.The five-year survival rates for cases with grade 1,grade 2 and grade 3 were 100% ,83.3% and 46.6% ,respectively.The difference between cases with grade 2 and grade 3 was statistically significant (P =0.027).The death rate during follow-up for cases with grade 1,grade 2 and grade 3 were 0,16.7% and 42.9% ,respectively.The difference between cases with grade 1 and grade 3 was statistically significant ( P - 0.001).Univariate analysis showed that grade of stromal invasion (P = 0.001),pathologic stage (P<0.001),presence of lymphovascular permeation (P < 0.001) and lymph node involvement　(P < 0.001) represented important prognostic factors.Multivariate analysis also showed that pathologic stage (P <0.001) was an independent prognostic factor.Conclusions The grading system of stromal invasion in pulmonary adenocarcinoma correlates with tumor prognosis and other prognostic factors.It represents a useful criterion in prognostic categorization of pTl adenocarcinoma of lung.     

pT1期肺腺癌间质浸润的分级及预后意义

Objective To study the prognostic significance of grading system for stromal invasion in pathologic tumor stage Tl (pTl) adenocarcinoma of lung.Methods Eighty-five cases of surgically resected pTl lung adenocarcinoma with clinicopathologic and follow-up data were retrospectively reviewed.The degree of invasive growth was classified into three grades according to its location in the tumor.The clinicopathologic characteristics and prognostic significance were analyzed.Results Amongst the 85 cases studied,17 cases (20% ) were in grade 1,12 (14% ) in grade 2 and 56 (66% ) in grade 3.The tumor size was smaller and lymphovascular permeation was less frequently encountered in cases with grade 1 stromal invasion than in those with grade 3 (P =0.005 for tumor size and P =0.018 for occurrence of lymphovascular permeation).The rate of lymph node metastasis and pathologic staging in cases with grade 1 and grade 2 were similar and were significantly lower than those with grade 3 ( P = 0.007 for rate of lymph node metastasis in grade 1 versus grade 3 tumors,P = 0.002 for pathologic stage in grade 1 versus grade 3 tumors,P = 0.027 for rate of lymph node metastasis in grade 2 versus grade 3 tumors and P =0.021 for pathologic stage in grade 2 versus grade 3 tumors).There was no statistically significant difference with respect to age,gender and smoking history of the patients,amongst cases in different grades.The overall five-year survival rate was 63%.The five-year survival rates for cases with grade 1,grade 2 and grade 3 were 100% ,83.3% and 46.6% ,respectively.The difference between cases with grade 2 and grade 3 was statistically significant (P =0.027).The death rate during follow-up for cases with grade 1,grade 2 and grade 3 were 0,16.7% and 42.9% ,respectively.The difference between cases with grade 1 and grade 3 was statistically significant ( P - 0.001).Univariate analysis showed that grade of stromal invasion (P = 0.001),pathologic stage (P<0.001),presence of lymphovascular permeation (P < 0.001) and lymph node involvement　(P < 0.001) represented important prognostic factors.Multivariate analysis also showed that pathologic stage (P <0.001) was an independent prognostic factor.Conclusions The grading system of stromal invasion in pulmonary adenocarcinoma correlates with tumor prognosis and other prognostic factors.It represents a useful criterion in prognostic categorization of pTl adenocarcinoma of lung.     

pT1期肺腺癌间质浸润的分级及预后意义

Objective To study the prognostic significance of grading system for stromal invasion in pathologic tumor stage Tl (pTl) adenocarcinoma of lung.Methods Eighty-five cases of surgically resected pTl lung adenocarcinoma with clinicopathologic and follow-up data were retrospectively reviewed.The degree of invasive growth was classified into three grades according to its location in the tumor.The clinicopathologic characteristics and prognostic significance were analyzed.Results Amongst the 85 cases studied,17 cases (20% ) were in grade 1,12 (14% ) in grade 2 and 56 (66% ) in grade 3.The tumor size was smaller and lymphovascular permeation was less frequently encountered in cases with grade 1 stromal invasion than in those with grade 3 (P =0.005 for tumor size and P =0.018 for occurrence of lymphovascular permeation).The rate of lymph node metastasis and pathologic staging in cases with grade 1 and grade 2 were similar and were significantly lower than those with grade 3 ( P = 0.007 for rate of lymph node metastasis in grade 1 versus grade 3 tumors,P = 0.002 for pathologic stage in grade 1 versus grade 3 tumors,P = 0.027 for rate of lymph node metastasis in grade 2 versus grade 3 tumors and P =0.021 for pathologic stage in grade 2 versus grade 3 tumors).There was no statistically significant difference with respect to age,gender and smoking history of the patients,amongst cases in different grades.The overall five-year survival rate was 63%.The five-year survival rates for cases with grade 1,grade 2 and grade 3 were 100% ,83.3% and 46.6% ,respectively.The difference between cases with grade 2 and grade 3 was statistically significant (P =0.027).The death rate during follow-up for cases with grade 1,grade 2 and grade 3 were 0,16.7% and 42.9% ,respectively.The difference between cases with grade 1 and grade 3 was statistically significant ( P - 0.001).Univariate analysis showed that grade of stromal invasion (P = 0.001),pathologic stage (P<0.001),presence of lymphovascular permeation (P < 0.001) and lymph node involvement　(P < 0.001) represented important prognostic factors.Multivariate analysis also showed that pathologic stage (P <0.001) was an independent prognostic factor.Conclusions The grading system of stromal invasion in pulmonary adenocarcinoma correlates with tumor prognosis and other prognostic factors.It represents a useful criterion in prognostic categorization of pTl adenocarcinoma of lung.     

肺腺癌中微乳头结构临床病理及预后意义的探讨

目的探讨肺腺癌中微乳头结构对肿瘤侵袭行为及其对预后的影响。方法选择具有完整临床病理及随访资料结果的肺腺癌91例,将病例分成微乳头结构阳性组（41例）和阴性组（50例）。阳性组按照该成分占肿瘤的多少又分成微乳头结构＋（占肿瘤的1％～10％）,＋＋（占肿瘤的11％～30％）,＋＋＋（超过肿瘤的30％）。结果总的5年生存率是64．8％。临床分期5年生存率分别为Ⅰ期88．9％、Ⅱ期46．2％、Ⅲ期23．8％。不同临床分期病例间的生存率差异有统计学意义（P=0．000）。微乳头结构含量多少与临床分期、肿瘤大小和5年生存率无关,P值分别是0．065、0．358、0．206。而微乳头结构阳性组和阴性组5年生存率分别是：41．5％和84．0％,P=0．000,且淋巴结转移率前者（65．9％）明显高于后者（20．0％）,P=0．000。有无微乳头结构与临床分期和肿瘤大小有关,P值均为0．000,即分期越晚,肿瘤越大,出现此结构的几率越高。而有无微乳头结构与性别、吸烟史无关。同一临床分期中阳性组与阴性组5年生存率分别是：Ⅰ期：78．6％、92．6％（P=0．1548）;Ⅱ期：30．0％,100％（P=0．0598）;Ⅲ期：17．7％,28．6％（P=0．4045）,但差异无统计学意义。结论肺腺癌中微乳头结构成分提示肿瘤高侵袭转移行为,是影响预后的重要因素,该病理形态的出现应提醒临床采取积极治疗措施并密切随访。     

基于生物信息学探索系统性硬化病相关肺动脉高压免疫相关基因及免疫细胞浸润分析北大核心CSCD

目的:通过生物信息学分析鉴定系统性硬化病相关肺动脉高压(SSc-PAH)免疫相关基因(IRGs),并深入探讨免疫细胞浸润在SSc-PAH中的作用。方法:从GEO数据库下载数据集GSE22356,使用R软件对其进行差异表达基因(DEGs)分析。通过ImmPort数据库下载人类免疫基因数据集,与DEGs取交集得到差异免疫相关基因(DEIRGs),对DEIRGs进行GO和KEGG富集分析。通过Cytoscape软件构建DEIRGs的蛋白互作(PPI)网络,根据Degree值筛选枢纽免疫基因。CIBERSORT算法评估SSc和SSc-PAH患者血液组织免疫细胞浸润。对枢纽免疫基因与浸润性免疫细胞进行相关性分析。结果:共得到56个DEIRGs。功能富集表明DEIRGs在信号转导、免疫应答、趋化作用中具有重要意义。根据PPI网络及Degree值得到枢纽免疫基因FCGR3B、CD28、LYN、LCK。免疫细胞浸润结果显示,与SSc相比,SSc-PAH患者血液组织中单核细胞、嗜中性粒细胞比例升高,而初始CD4 T细胞、未活化的CD4记忆性T细胞、γδ T细胞比例降低。相关性分析结果显示,CD28、LCK与γδ T细胞呈正相关,与单核细胞呈负相关。FCGR3B与中性粒细胞呈正相关,与初始CD4 T细胞呈负相关,LYN与单核细胞呈正相关,与γδ T细胞呈负相关。结论:枢纽免疫基因和免疫细胞浸润差异在SSc-PAH发生发展中起重要作用。     

基于生物信息学筛选并分析与浸润性乳腺癌免疫浸润有关的预后基因北大核心CSCD

目的:筛选并分析浸润性乳腺癌(BRCA)发生发展过程中与免疫浸润有关的预后基因,为进一步寻找BRCA潜在的预后生物标志物及治疗靶点奠定基础。方法:从TCGA数据库下载BRCA患者的mRNA表达信息数据和临床数据,并进行预处理,ESTIMATE网站获取患者的免疫/基质评分;分析免疫/基质评分与临床病理分期TNM系统间及与总生存率间的关系。按照评分中位数分别将患者分为高免疫评分组和低免疫评分组,基质评分分组同上,利用R软件分别筛选差异表达基因(DEGs),并取交集;对上步取交集的DEGs进行GO和KEGG富集分析;通过Cytoscape软件构建蛋白互作(PPI)网络,并筛选出枢纽基因。利用GSEA分析肿瘤免疫相关基因富集的主要通路;运用GEPIA2.0数据库分析枢纽基因在肿瘤与癌旁组织的表达情况及与总生存期的关系。结果:筛选出1 244个与BRCA免疫浸润相关的DEGs,富集分析表明这些基因主要参与信号转导、免疫反应、炎症反应等生物学过程;GSEA富集分析表明这些基因主要参与趋化因子信号通路、TOLL样受体信号通路、JAKSTAT信号通路及T细胞受体信号通路等。PPI网络筛选出CD19、IL-2、PTPRC、CD28、IL-6、CD40LG和CCR7共7个枢纽基因;GEPIA2.0数据库分析结果显示IL-2、CD40LG和CCR7与患者总生存率显著相关。结论:筛选出IL-2、CD40LG及CCR7基因与BRCA免疫浸润密切相关,并具有预后价值,为进一步预测BRCA患者预后的生物标志物及治疗靶点奠定基础。     

pT1期肺腺癌TK1的表达及其预后意义

目的 探讨细胞质胸苷激酶1(cytosolic thymidine kinase 1,TK1)在TNM病理分期T1期(pT1)肺腺癌中的表达及预后意义.方法 选择具有完整临床病理及随访资料结果的pT1期肺腺癌80例,应用免疫组织化学方法(EnVision法)检测TK1的表达情况,研究TK1表达与临床病理特征的关系,并分析该指标本身及与间质浸润分级相结合对肿瘤预后的评估作用.结果 TK1表达:12例(15%)表达"-",27例(33.8%)表达"+",31例(38.8%)表达"(++)",10例(12.5%)表达"(+++)".5年存活者:TK1"-"(87.5%)与"+"(82.1%)相似,"(++)"(35%)与"(+++)"(51.3%)相似,其余各表达强度病例间均有差异.据此将本组病例分为预后好的TK1"-/+"表达组(41例)以及预后差的TK1"(++)/(+++)"表达组(39例).TK1"(++)/(+++)"表达组的淋巴管/血管侵犯率(P=0.019)、淋巴结转移率(P=0.002)、间质浸润分级(P＜0.001)及临床病理分期(P＜0.001)均高于TK1"-/+"表达组,性别、年龄、肿瘤直径及吸烟史两组间的差异无统计学意义.本组病例的间质浸润分级:0级:7例(9%),1级:10例(12%),2级:12例(15%),3级:51例(64%),间质浸润分级0级、1级及2级病例的预后相似并好于3级病例,而3级病例中TK1表达"-/+"者的5年生存率高于TK1表达"(++)/(+++)"者(P=0.006),且与0～2级病例相似.结论 pT1期肺腺癌中TK1表达与肿瘤侵袭性及预后密切相关,并可与间质浸润分级相结合对肿瘤预后进行更加准确的评估.     

CAFs与肺腺癌患者临床病理特征及肿瘤浸润免疫细胞的相关性研究

目的观察α-SMA+的肿瘤相关成纤维细胞(cancer-associated fibroblasts,CAFs)与肺腺癌患者临床病理特征及肿瘤浸润免疫细胞的相关性,为认识CAFs在肺腺癌发生中的作用提供依据,并将为临床肺腺癌的诊疗提供新思路。方法收集56例临床手术切除且病理诊断为原发肺腺癌的肿瘤组织标本,收集患者一般情况及临床病理学特征等资料。免疫组织化学染色方法检测肺腺癌患者肿瘤标本中α-SMA、CD4、CD8及CD33的表达情况,病理学方法计数间质细胞及α-SMA阳性的CAFs,统计学方法分析CAFs比例与患者临床病理特征及肿瘤浸润免疫细胞的相关性。结果α-SMA+CAFs比例与患者吸烟及肿瘤TNM(tumor,node,metastasis)分期呈正相关(P<0.05),与肿瘤分化程度呈负相关(P<0.05),但与患者年龄、性别及肿瘤浸润CD4+T细胞、CD8+T细胞及MDSCs(myeloid-derived suppressor cells,MDSCs)的数量无明显相关。结论α-SMA+CAFs与肺腺癌的发生发展密切相关,其与肿瘤临床分期及分化程度的相关性提示其在肺腺癌的发生发展中起促进作用,对其深入机制的阐明将有助于完善肺腺癌的发生机制并将为其治疗提供新思路。