非小细胞肺癌中表皮生长因子受体基因突变的筛查

目的检测非小细胞肺癌患者的表皮生长因子受体(EGFR)基因外显子的突变情况。方法收集24例肺腺癌和25例肺鳞癌手术标本,抽提组织DNA,对EGFR基因的1-28号外显子进行扩增并测序,筛查EGFR基因的突变。结果在8例肺腺癌患者中检出EGFR突变,在肺鳞癌患者中未检测到突变。检测到的突变位点位于19-21号外显子内,且均为非吸烟患者,占非吸烟肺腺癌患者的61.5%(8/13)。结论 EGFR基因突变在非吸烟的肺腺癌患者具有较高的发生率,突变主要集中发生于19-21号外显子。     

Epidermal growth factor receptor genotype in plasma DNA and outcome of chemotherapy in the Chinese patients with advanced non-small cell lung cancer

Background  The genotype of epidermal growth factor receptor (EGFR) is associated with tyrosine kinase inhibitor and effectiveness of therapy, but its role in cytotoxic chemotherapy is still unknown. Previous studies indicated that certain EGFR mutations were associated with response and progression free survival following platinum based chemotherapy. Our recent studies have identified that EGFR genotypes in the tumour tissues were not associated with response to the first-line chemotherapy in Chinese patients with advanced non-small cell lung cancer (NSCLC). In this study, we investigated associations of EGFR genotypes from plasma of patients with advanced NSCLC and response to first-line chemotherapy and prognosis.

Methods  We enrolled 145 advanced NSCLC patients who had received first-line chemotherapy in our department. We examined plasma EGFR genotypes for these patients and associations of EGFR mutations with response to chemotherapy and clinical outcomes.

Results  There were 54 patients with known EGFR mutations and 91 cases of wild types. No significant difference was detected in the response rate to first-line chemotherapy between mutation carriers and wild-type patients (37.0% vs. 31.9%). The median survival time and 1-, 2-year survival rates were higher in mutation carriers than wild-types (24 months vs. 18 months, 85.7% vs. 65.7% and 43.7% vs. 25.9%, P=0.047). Clinical stage (IV vs. IIIb), response to the first-line chemotherapy (partial vs. no) and EGFR genotype were independent prognostic factors.

Conclusion  Plasma EGFR mutations in the Chinese patients with advanced NSCLC is not a predictor for the response to first-line chemotherapy, but an independent prognostic factor indicating longer survival.

     

晚期非小细胞肺癌胸腔积液表皮生长因子受体突变检测对厄洛替尼疗效的预测价值

目的:探讨非小细胞肺癌（NSCLC）患者胸腔积液（胸液）表皮生长因子受体（EGFR）突变对厄洛替尼疗效的预测价值。方法:应用实时荧光定量PCR-HRM法检测275例NSCLC患者胸液标本EGFR突变,其中有组织标本的52例同时进行HRM法和直接测序法检测,比较胸液与组织EGFR突变状态的一致性和可重复性。胸液EGFR敏感突变患者随机给予厄洛替尼治疗或吉西他滨加顺铂（GP）方案化疗。比较2组客观缓解率（ORR）和中位无进展生存期（mPFS）。结果:275例NSCLC患者胸液EGFR敏感突变率为55.3%。52例配对组织、胸液标本中,EGFR敏感突变检出率为61.5%,高于直接测序法的40.3%（P<0.01）;胸液标本中,EGFR敏感突变检出率为55.8%,高于直接测序法的36.5%（P<0.01）。胸液和组织检测EGFR敏感突变的吻合率为82.6%;厄洛替尼组mPFS 11.5个月（95%CI 10.4~12.6）,显著高于GP组的4.4个月（95%CI 3.9~4.8）（P<0.01）。厄洛替尼组ORR明显高于GP组（70.0% vs 29.4%,P<0.01）。结论:晚期NSCLC胸液标本可弥补或替代组织标本进行EGFR敏感突变检测,HRM法敏感性优于直接测序法。EGFR敏感突变NSCLC患者应用厄洛替尼可提高客观缓解率,延长mPFS。     

非小细胞肺癌组织中表皮生长因子受体和血管内皮生长因子的表达及临床意义

目的:观察非小细胞肺癌(NSCLC)组织中表皮生长因子受体(EGFR)和血管内皮生长因子(VEGF)的表达,并探讨二者可能的临床意义.方法:免疫组织化学染色比较82例NSCLC和20例非恶性肺组织中EGFR和VEGF的表达;观察NSCLC患者不同临床病理特征下EGFR和VEGF蛋白的表达情况,并分析二者表达的相关性.结果:NSCLC组织中EGFR、VEGF阳性表达率明显高于非恶性肺组织(53.66% vs 0,62.20% vs 25%,P＜0.05).EGFR表达在不同性别、不同病理类型(鳞癌vs腺癌)、有无淋巴结转移及不同TNM分期的NSCLC患者之间有统计学差异(P＜0.05);VEGF表达在有无淋巴结转移及不同TNM分期的NSCLC患者之间有统计学差异(P=0.000 1).EGFR、VEGF高表达患者生存期短于各自的低表达患者(P＜0.05).NSCLC组织中EGFR和VEGF的表达具有相关性(rs=0.314,P＜0.05).结论:NSCLC组织中EGFR和VEGF存在过度表达,二者表达具有相关性,可作为判断NSCLC患者病情及预后的参考指标和靶向治疗靶点.     

EGFR-TKIs一线治疗EGFR敏感突变非小细胞肺癌患者的预后分析

目的 探讨影响EGFR-TKIs一线治疗表皮生长因子受体(epidermal growth factor receptor,EGFR)敏感突变晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的预后因素.方法 收集2010-2013年本院接受EGFR-TKIs一线治疗,并获得中国癌症基金会赠药的EGFR敏感突变晚期NSCLC患者1 14例.应用COX回归分析接受厄洛替尼/吉非替尼治疗后,影响患者脑转移进展发生和1、2、3年生存的预后因素,并进一步应用Kaplan-Meier法比较19和21外显子突变患者脑转移中位进展时间(time to neurological progression,nTTP)的差异.结果 114例患者中,17例治疗前即存在脑转移,14例在TKIs治疗期间出现脑转移,77.4％ (24/31)在随访截止前出现脑转移进展.单因素分析显示:接受EGFR-TKIs治疗后,年龄＜60岁和≥60岁患者的1、2、3年生存率分别为90.15％、78.50％、63.30％和92.05％、57.90％、28.40％ (P =0.038);曾接受和未接受手术者的1、2、3年生存率分别为92.90％、86.45％、48.90％和90.85％、61.65％、27.30％ (P =0.034);无和有骨转移患者6、12、18个月脑转移进展发生率分别为3.40％、4.55％、10.90％和3.00％、11.70％、23.60％(P=0.046).多因素分析显示:年龄≥60岁是EGFR-TKIs治疗中的独立死亡风险因素(P =0.024);19和21外显子突变患者nTTP分别为18.3个月和13.0个月(P =0.276).结论 ＜60岁的EGFR敏感突变NSCLC患者接受TKIs治疗具有更低死亡风险,而合并骨转移者易发生脑转移,其中19外显子缺失突变脑转移患者具有更能从TKIs治疗获益的趋势.     

无症状脑转移表皮生长因子受体突变非小细胞肺癌患者脑部放疗的最佳时机

目的：探讨表皮生长因子受体（ EGFR）突变阳性、无症状脑转移的非小细胞肺癌（ NSCLC）患者脑部放疗（ BRT）的最佳时机。方法选取50例初诊无症状脑转移的EGFR突变阳性的肺腺癌患者,分析其治疗方案、疗效以及失败模式。结果50例患者的中位随访时间为26个月,2年总生存率为44.0％,预期生存时间为21个月。单因素分析显示ECOG评分、颅外转移灶、一线全身治疗方案与总生存期显著相关。多因素分析显示仅颅外转移灶与总生存期相关。所有患者2年脑转移无进展生存率为29.3％,预期时间为19个月。 BRT时机与脑转移无进展生存时间无明显相关性。结论对于无症状脑转移的EGFR突变阳性的NSCLC患者,一线BRT无明显生存获益,一线应用酪氨酸激酶抑制剂基础上延迟BRT可能是较好的治疗选择。     

早期非小细胞肺癌表皮生长因子受体基因突变分布

目的探索早期非小细胞肺癌（NSCLC）表皮生长因子受体（EGFR）基因突变状况。方法以上海市胸科医院2003年6月1日--2011年6月1日期间早期NSCLC患者为研究对象,收集NSCLC根治术后原发灶标本,采用PCR扩增和直接测序方法检测EGFR突变;EGFR敏感突变和非敏感突变患者之间临床病理特征比较采用x。检验。采用Logistic回归法分析EGFR敏感突变与临床病理特征的相关性。结果共入组165例NSCLC患者,其中EGFR野生型93例（56．36％,93／165）,EGFR突变72例（43．64％,72／165）,敏感突变56例（19del33例和21L858R23例）,占总人群33．94％（56／165）,占所有突变77．78％（56／72）;单因素分析发现,腺癌、不吸烟、原发灶直径〈5cm和EGFR荧光原位杂交（FISH）扩增阳性患者突变概率较高;Logistic回归分析显示,病理类型及原发灶大小是早期NSCLC患者EGFR敏感突变的独立预测因子,腺癌、肿瘤直径〈5cm患者的EGFR突变概率分别是非腺癌、肿块直径≥5cm患者的4．435倍（95％CI1．209～16．273,P：0．025）、4．343倍（95％CI1．393～13．540,P=0．011）。结论在早期NSCLC患者中,腺癌、不吸烟、原发灶直径〈5em和EGFRFISH扩增阳性患者的敏感突变概率高;病理类型及肿瘤大小是早期NSCLC患者EGFR敏感突变的独立预测因子。     

Erlotinib as a salvage treatment for patients with advanced non-small cell lung cancer after failure of gefitinib treatment

Background  Several clinical trials showed that erlotinib was effective after the failure of gefitinib in advanced non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the feasibility of erlotinib treatment after the failure of gefitinib based on the data from our hospital.

Methods  The clinical data of 20 patients with advanced NSCLC who were admitted to Shanghai Chest Hospital from August 2007 to December 2008 were retrospectively analyzed. All of the patients were given erlotinib treatment after the failure of gefitinib. Survival analysis was made by Kaplan-Meier method. The Cox regression model was performed to analyze the relationship between the influential factors and the erlotinib progression-free survival (PFS).

Results  Five patients had a partial response (PR), nine patients had stable disease (SD) and six patients had progressive disease (PD) with gefitinib treatment. The median PFS was 277 days (95% CI 0–566). No patient had a PR, seven had SD and fourteen PD with the erlotinib therapy. The median PFS was 31 days (95% CI 9.1–52.9). The response rate (RR) was 0, and the disease control rate (DCR) was 35% (7/20). Cox regression analysis demonstrated that sex (P=0.96), age (P=0.89), smoking history (P=0.78), performance status (PS) (P=0.98), gefitinib efficacy (P=0.90) and whether chemotherapy was applied between using the two drugs (P=0.45) had no significant correlation with erlotinib PFS. Fifteen patients had epidermal growth factor receptor (EGFR) mutation status determined. There were five cases got SD with the erlotinib treatment in ten mutation negative (wild-type) patients. No SD was recorded in the five mutation positive patients.

Conclusions  The efficacy of erlotinib treatment after gefitinib failure was limited. However, the patients who are EGFR mutation negative can probably benefit from erlotinib treatment after gefitinib failure.

     

晚期非小细胞肺癌患者表皮生长因子受体基因突变状态研究

目的：探讨晚期非小细胞肺癌（non-small-cell carcinoma,NSCLC）患者肺组织或胸水表皮生长因子受体（epider-mal growth factor ,EGFR）基因突变状态,以期为肺癌患者选择靶向治疗提供依据。方法选择经组织学或细胞学确诊为中晚期NSCLC 患者118例,采用扩增受阻突变系统（ ARMS ）-qPCR方法,对不同途径获取的肺组织或胸水细胞块进行EGFR基因（18～21外显子）突变情况测定。结果（1）118例晚期NSCLC患者, EGFR基因突变者45例,突变率为38．1％,其中男性占44.4％,女性占55．6％;（2）不同途径采集的标本,EGFR基因突变率不同,以手术切除和CT引导肺活检标本阳性率较高,胸水细胞块阳性率较低,与前两者比较,差异均有统计学意义（P＜0．05）;（3）不同病期采集的胸水标本阳性率不同,随着肿瘤病情进展,阳性率有增高趋势,但各期比较,差异无统计学意义（P＞0．05）;（4）在EGFR基因突变患者中,以19外显子缺失（占40.0％）和21外显子L858R点突变（占42．2％）比例较高,18外显子缺失（占8．9％）和20外显子缺失（占6．7％）相对较低,后两者与前两者比较,差异均有统计学意义（P＜0．05）;另外发现2例（4．4％）患者为19和21外显子同时突变,其余43例（95.6％）为单基因突变,未发现多基因突变的情况。结论对晚期NSCLC患者应尽可能作EGFR基因检测,以期为选择分子靶向（ TKIs）治疗提供依据。     

Epidermal growth factor receptor mutations detected in tumors from Chinese “never smokers” with lung adenocarcinoma

Lung cancer is the leading cause of cancerrelated death in the world as well as in China. It is estimated that approximately 429 000 Chinese individuals may die from lung cancer in 2005, and the mortality rate for lung cancer will double in the next century.^1 Currently, chemotherapy is the a main treatment of advanced and recurrent lungcancer. However,     

非小细胞肺癌中EGFR突变与雌激素受体表达的相关性研究

目的 探讨非小细胞肺癌(NSCLC)组织中雌激素受体α(ERα)的表达与表皮生长因子受体(EGFR)突变之间的关系.方法 应用免疫组织化学法及实时荧光定量聚合酶链反应法检测286例NSCLC中ERα的表达及EGFR突变情况,并分析其与临床特性的关系.结果 ERα表达阳性率为36.0％ (103/286),在女性患者中的表达要显著高于男性患者(P=0.004),肿瘤最大直径小于或等于3 cm的患者显著高于肿瘤直径大于3 cm的患者(P＜0.01).EGFR基因突变62例(21.7％),在女性、腺癌、肿瘤直径较小的患者显著增多,在ERα表达阳性患者中显著高于ERα阴性者(P=0.001).结论 NSCLC中ERα的阳性表达与EGFR基因突变相关,可能与EGFR信号通路的交叉调控有关.     

EGFR和c-Met基因的相对拷贝数在非小细胞肺癌预后中的意义

目的通过研究非小细胞肺癌(NSCLC)病人组织中表皮生长因子受体(EGFR)和c-Met的DNA相对拷贝数的变化,探讨EGFR和c-Met基因在NSCLC发生发展和预测预后过程中的作用。方法采用实时荧光定量PCR方法检测61例NSCLC病人组织中EGFR和c-Met的DNA相对拷贝数,分析它们之间的相关性,以及与各种临床病理特征的关系,并进行生存分析比较。结果 EGFR和c-Met的DNA相对拷贝数的相关系数r=0.352,P=0.005,呈显著性正相关。EGFR和c-Met DNA在吸烟患者中的相对拷贝数分别为0.15和0.13,均高于不吸烟患者;在腺癌中的相对拷贝数分别为0.16和0.14,均高于鳞癌,上述差异经检验有统计学意义(P<0.05)。在鳞癌患者中,EGFR和c-Met DNA相对拷贝数越高则预后越差,经Log-Rank检验,两组病例生存差别有统计学意义(P=0.015,P=0.046)。结论 EGFR和c-Met在NSCLC的发生和发展中可能存在相互或协同作用,能够对鳞癌患者进行预后评估。     

Efficacy and clinical/molecular predictors of erlotinib monotherapy for Chinese advanced non-small cell lung cancer

Background A retrospective analysis of clinical data were conducted reviewing patients who were given erlotinib at Peking Union Medical College （PUMC） Hospital from May 2005 to December 2009. Relationships between clinical factors, epidermal growth factor receptor （EGFR） mRNA expression, EGFR gene mutations, KRAS gene mutations and clinical outcomes were investigated in Chinese patients with advanced non-small cell lung cancer （NSCLC）. Methods Patients with stage ⅢB/Ⅳ NSCLC who had not previously participated in erlotinib related clinical trials were enrolled into this study. All patients were given oral erlotinib 150 mg per day. Tumor samples of some patients were accessed with mutant-enriched polymerase chain reaction assay （EGFR, KRAS gene mutations） and multiplex branched DNA assay （EGFR mRNA expression）. Results Seventy-nine patients were enrolled in this study, 23 patients had a partial response （PR）, 36 patients had a stable disease （SD）, 20 patients had a PD, with an objective response rate of 29.1%, and a disease control rate of 74.7%. Females （P=0.023）, non-smokers （P=0.013）, patients with a skin rash （P=0.047）, and with highly differentiated tumors （P=0.037） were significantly correlated with the objective response rate. Patients with a lower ECOG PS （P=0.002）, highly differentiated tumors （P=0.014）, non-smokers （P=0.002）, and patients with a skin rash （P 〈0.001） were significantly correlated with the disease control rate. The median progression-free survival was 35 weeks （95% CI： 13-57 weeks） and 1-year survival was 72.3%. Highly-differentiated tumors （P=0.027） and patients with a skin rash （P 〈0.001） were significantly correlated with PFS. Seventeen patients were tested for EGFR/KRAS gene mutations and EGFR mRNA expression. Progression-free survival （PFS） of patients with EGFR exon 19/21 mutations was 66 weeks, longer than patients with wild type EGFR exon 19/21 （P=0.018）. No significant relationships were found between EGFR mRNA expression, EGFR exon 19/21 mutations, and KRAS mutations and objective response rate or disease control rate. The most common adverse events were skin rash （60.9%） and diarrhea （26.6%）. Conclusions Erlotinib was safe and effective in treating Chinese patients with advanced NSCLC. The PFS of patients who had a skin rash, highly differentiated tumors, or EGFR exon 19/21 mutations was significantly longer.     

70例非小细胞肺癌表皮生长因子受体的检测分析

目的探讨表皮生长因子受体(EGFR)在非小细胞肺癌(NSCLC)中的表达特征及其临床病理意义。方法采用免疫组化染色Envision法检测EGFR在70例NSCLC中和12例健康肺组织中的表达。结果在70例NSCLC患者中,EGFR高表达率为72.9%,与健康肺组织比较差异有统计学意义(P<0.05),EGFR高表达与年龄、性别、肿瘤大小、组织学类型及病理分级间无关(P>0.05),与TNM分期、淋巴结转移显著相关(P<0.05),且其表达水平与TNM分期及淋巴结转移呈正相关。结论 (1)EGFR蛋白过表达与NSCLC的发生有密切关系;(2)EGFR蛋白过表达与NSCLC患者TNM分期及淋巴结转移相关,说明其过表达与肺癌的进展、转移有关。     

盐酸埃克替尼治疗晚期非小细胞肺癌的临床疗效观察

目的:观察盐酸埃克替尼治疗晚期非小细胞肺癌的临床疗效及安全性。方法:回顾分析埃克替尼治疗30例晚期非小细胞肺癌的临床效果,采用口服治疗,125 mg/次,3次/d,评价其近期疗效、无病进展生存期及不良反应。结果:30例患者在接受埃克替尼1个月治疗后,完全缓解（CR）0例,部分缓解（PR）10例,疾病稳定（SD）14例,疾病进展（PD）6例,客观有效率（ORR）为33.3%,疾病控制率（DCR）为80%。在各临床因素中,ECOG评分及是否伴有脑转移与近期疗效具有相关性（P<0.05）。截至随访结束,24例（80%）出现PFS终点事件,全组中位PFS为8.0个月。患者的PFS主要与患者年龄、吸烟与否、ECOG评分以及是否伴有其他部位的转移有关（P<0.05）。全组不良反应发生率为43.3%,主要为皮疹5例（16.7%）,皮肤瘙痒2例（6.7%）,腹泻 1例(3.3% ),胃部不适1例( 3.3%),肝功能轻度损害6例(20.0% )。结论:盐酸埃克替尼治疗晚期非小细胞肺癌疗效肯定,耐受性好。     

表皮生长因子受体酪氨酸激酶抑制剂治疗晚期非小细胞肺癌临床观察

目的评价表皮生长因子受体酪氨酸激酶抑制剂(EGFRT-TKI)治疗晚期非小细胞肺癌(NSCLC)的疗效及安全性。方法晚期NSCLC患者160例使用EGFR-TKI吉非替尼或厄洛替尼治疗,其中77例(48.1%)为一线治疗组,83例(51.9%)为二线治疗组。观测其临床特征、治疗效果及生存时间,并对药物安全性进行评估。结果EGFR—TKI治疗总有效率为33.8%(54/160),疾病控制率为74.4%(119/160)。无进展中位生存时间为9.8个月,中位生存时间为14.5个月,1年生存率为55%。Logistic多因素回归分析显示,病理类型、皮疹情况和血清CEA变化与有效率相关(P均<0.05);病理类型、吸烟史、皮疹情况、血清CEA变化与疾病控制率相关(P均<0.05);病理类型为影响无进展生存的独立因素,PS评分为影响生存的独立因素。一线治疗、二线治疗疗效相当。药物不良反应主要表现为皮疹和轻度腹泻。结论 EGFR—TKI治疗晚期NSCLC安全有效。     

肺腺癌患者血浆及尿中表皮生长因子受体突变研究

目的:分析血浆和尿中进行表皮生长因子受体(epidermal growth factor receptor,EGFR)突变检测的可行性。方法:利用改良酚-氯仿方法从血浆和尿中提取DNA,突变富集型PCR技术扩增EGFR外显子19和21,进行基因测序。结果:60例进展期肺腺癌患者中,血浆中检测出12例EGFR突变,其中外显子19缺失突变7例,外显子21点突变5例,尿标本中未检测出突变。血浆EGFR突变与性别相关,与年龄、吸烟史无相关。结论:在进展期肺腺癌患者血浆标本中可检测出EGFR突变,尿标本中未检测出EGFR突变。     

非小细胞肺癌314例EGFR基因突变的研究

目的研究中国人非小细胞肺癌表皮生长因子受体（EGFR）基因突变的情况及其与临床特征（性别、临床分期、吸烟情况）的关系。方法采用PCR扩增和基因测序检测314例非小细胞肺癌（NSCLCs）EGFR外显子19和21的突变情况,分析其突变与临床特征的关系。结果314例中共检测出120例（38．2％）EGFR突变,EGFR基因突变与性别和吸烟史相关,与临床分期无关。结论中国人NSCLCs的EGFR突变率较高,在使用EGFR酪氨酸激酶抑制剂治疗前进行EGFR基因突变检测很有必要。     

Detecting the epidermal growth factor receptors status in non-small cell lung cancer

Non-small cell lung cancer is one of the leading causes of all cancer deaths, but despite years of research, it is still difficult to predict the response and clinical outcome of the disease. In recent years, new treatment strategies targeting the epidermal growth factor receptors (EGFR) have been developed. EGFR is one of the most frequently over expressed proteins in various cancers, including lung cancer, and signaling through this receptor has been known to cause tumor progression as well as resistance to different treatments. Therefore, EGFR has become an attractive target for various treatment strategies. However, it is important to note that not all patients with lung cancer are suitable for targeted treatment, and that patients should be selected for this treatment. Several studies have proven that the status of the EGFR can be both an indicator of suitability for treatment with, and predict the likelihood of response to EGFR targeted therapy. There are many standard techniques to be used for the detection of EGFR. This overview summarizes the ongoing and future investigations to determine the status of the EGFR.

     

非小细胞肺癌血浆EGFR突变与肿瘤标志物水平的关系

目的 探讨非小细胞肺癌外周血游离DNA样本EGFR突变率与临床基线特征和血清肿瘤标志物表达水平的关系.方法 收集本院确诊为非小细胞肺癌166例.利用PCR和变性高效液相色谱法分析EGFR19和21外显子突变.其中89例同时利用多肿瘤标志物蛋白芯片检测系统检测癌胚抗原(CEA)、糖类抗原125(CA125)、糖类抗原153(CA153)等血清肿瘤标志物,分析突变率与临床基线特征和肿瘤标志物表达水平的关系.结果 166例非小细胞肺癌中,EGFR总突变率19.9％.女性突变率显著高于男性(P =0.037).腺癌突变率高于其他组织学类型,但未达到显著水平(P =0.096).CEA、CA153中高表达患者EGFR突变率显著高于低表达者(P =0.048,P=0.017),CA199高表达患者仅有高于中低表达者的趋势(P =0.093).多变量Logistic分析表明,组织学类型为腺癌,CA153、CEA中、高表达与EGFR突变率相关.结论 对于晚期非小细胞肺癌,血浆EGFR突变率与血清肿瘤标志物表达水平明显相关.其标志物水平可作为进一步判断EGFR突变优势群体的因素.