表皮生长因子受体基因突变对非小细胞肺癌临床病理与酪氨酸激酶抑制剂临床疗效的影响
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摘要
目的探究表皮生长因子受体(EGFR)基因突变对非小细胞肺癌(NSCLC)临床病理及酪氨酸激酶抑制剂(TKI)临床疗效的影响。方法选取2017年1-12月于我院进行治疗的460例NSCLC患者为研究对象,按照其是否出现EGFR基因突变将其区分为突变阳性组(129例)与突变阴性组(331例),突变阳性组患者中区分为TKI组(72例)与化疗组(57例),突变阴性组患者均接受化疗(331例),分析EGFR基因突变与患者临床病理之间的关系,对比突变组TKI治疗、突变组化疗及非突变组化疗无进展生存期(PFS)。结果 (1)分析发现,NSCLC患者EGFR基因突变与患者性别、吸烟、病理类型、分化程度、血清癌胚抗原(CEA)水平均具有密切相关性(P <0.05)。(2)EGFR基因突变阳性患者中TKI组客观缓解率(ORR)及疾病控制率(DCR)均高于基因突变阳性患者中化疗组,对比差异具有统计学意义(P <0.05)。(3)EGFR突变阴性组患者化疗ORR及DCR均高于EGFR阳性患者中化疗组,对比差异具有统计学意义(P <0.05)。(4)EGFR突变患者中TKI组PFS为(201.65±20.81)d,突变化疗组PFS为(116.53±11.61)d,未突变化疗组PFS为(167.59±11.46)d,组间对比差异具有统计学意义(P <0.05)。结论 EGFR基因突变多发于女性、非吸烟、腺癌、血清CEA≥5 ng/mL的NSCLC患者中,出现EGFR突变患者采取TKI治疗能有效延长其PFS,但对无EGFR突变患者采取化疗的方式效果更佳。
Objective To explore the effect of epidermal growth factor receptor( EGFR) gene mutation on clinical pathology of non-small cell lung cancer(NSCLC) and clinical efficacy of tyrosine kinase inhibitor(TKI)treatment. Methods 460 NSCLC patients who were treated in our hospital from January 2017 to December 2017 were selected in this study. Based on types of mutations, they were divided into mutant positive group(129 cases)and mutant negative group(331 cases). The mutant positive group was further divided into TKI target treatment group(72 cases) and chemotherapy group(57 cases). All patients in the mutant negative group received chemotherapy(331 cases) treatment. Finally, the relationship between the EGFR gene mutation and clinical pathology was analyzed, and the progression-free survival( PFS) among groups of TKI therapy, chemotherapy of mutant positive group and chemotherapy of mutant negative group was compared. Results( 1) It was found that the mutation of EGFR gene in NSCLC patients was closely related to the sex, smoking, pathological type, degree of differentiation, and serum carcinoembryonic antigen(CEA) level(P < 0.05).(2) The ORR and DCR in patients treated with TKI were significantly higher than those in other patients with positive gene mutation(P < 0.05).(3) The ORR and DCR in the EGFR mutant negative group were significantly higher than those in the EGFR mutant positive group(P < 0.05).( 4) The PFS were significantly different among all groups(P<0.05):(201.65±20.81)d in TKI group;(116.53 ± 11.61) d in chemotherapy of mutant positive group and( 167.59 ± 11.46)d in mutant negative group. Conclusions The mutation of EGFR gene in NSCLC patients occurs more frequently in women, nonsmokers,adenocarcinoma, and those whose serum CEA ≥ 5 ng/mL.TKI therapy can effectively prolong the PFS in patients with EGFR positive mutation. However, it's more effective to use chemotherapy for patients without EGFR positive mutation.
Objective To explore the effect of epidermal growth factor receptor( EGFR) gene mutation on clinical pathology of non-small cell lung cancer(NSCLC) and clinical efficacy of tyrosine kinase inhibitor(TKI)treatment. Methods 460 NSCLC patients who were treated in our hospital from January 2017 to December 2017 were selected in this study. Based on types of mutations, they were divided into mutant positive group(129 cases)and mutant negative group(331 cases). The mutant positive group was further divided into TKI target treatment group(72 cases) and chemotherapy group(57 cases). All patients in the mutant negative group received chemotherapy(331 cases) treatment. Finally, the relationship between the EGFR gene mutation and clinical pathology was analyzed, and the progression-free survival( PFS) among groups of TKI therapy, chemotherapy of mutant positive group and chemotherapy of mutant negative group was compared. Results( 1) It was found that the mutation of EGFR gene in NSCLC patients was closely related to the sex, smoking, pathological type, degree of differentiation, and serum carcinoembryonic antigen(CEA) level(P < 0.05).(2) The ORR and DCR in patients treated with TKI were significantly higher than those in other patients with positive gene mutation(P < 0.05).(3) The ORR and DCR in the EGFR mutant negative group were significantly higher than those in the EGFR mutant positive group(P < 0.05).( 4) The PFS were significantly different among all groups(P<0.05):(201.65±20.81)d in TKI group;(116.53 ± 11.61) d in chemotherapy of mutant positive group and( 167.59 ± 11.46)d in mutant negative group. Conclusions The mutation of EGFR gene in NSCLC patients occurs more frequently in women, nonsmokers,adenocarcinoma, and those whose serum CEA ≥ 5 ng/mL.TKI therapy can effectively prolong the PFS in patients with EGFR positive mutation. However, it's more effective to use chemotherapy for patients without EGFR positive mutation.
引文
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[6]姚秀琴,徐韫健,付玉梅,等.非小细胞肺腺癌患者恶性胸水表皮生长因子受体基因突变的分析[J].实用医学杂志,2017,33(23):3980-3983.
[7]MARTIN P,SHIAU C J,PASIC M,et al.Clinical impact of mutation fraction in epidermal growth factor receptor mutation positive NSCLC patients[J].Br J Cancer,2016,114(6):616-622.
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[9]姚晓燕,申淑景,王晔,等.EGFR突变与非小细胞肺癌临床病理和TKI治疗疗效预测相关性分析[J].中华肿瘤防治杂志,2016,23(6):369-372.
[10]肖芸,罗辉,黄敏.表皮生长因子受体基因突变对非小细胞肺癌临床病理与酪氨酸激酶抑制剂疗效的影响[J].中国老年学,2017,37(23):5849-5851.
[11]王芬,王洁,白桦,等.晚期非小细胞肺癌EGFR蛋白磷酸化、基因突变与EGFR-TKI疗效相关性的研究[J].中国癌症杂志,2014,24(9):657-668.
[12]PARK I K,HYUN K,PARK S,et al.P3.16-013 prognostic effect of EGFR gene mutation for recurrence in completely resected lung adenocarcinoma[J].J Thoracic Oncol,2017,12(11):S2348.
[13]OSAWA M,OHASHI K,KUBO T,et al.Effect of vandetanib on lung tumorigenesis in transgenic mice carrying an activating Egfr gene mutation[J].Acta Medica Okayama,2016,70(4):243.
[14]HERNANDEZ M A,ALATORRE A J,GARIBAY J C,et al.LATE-BREAKING ABSTRACT:Treatment efficacy of afatinib vs gefitinib in lung adenocarcinoma with EGFR gene mutation[J].Eur Respira J,2016,48(suppl 60):PA2880.
[15]NARITA M,SHIMURA E,NAGASAWA A,et al.Chronic treatment of non-small-cell lung cancer cells with gefitinib leads to an epigenetic loss of epithelial properties associated with reductions in microRNA-155 and-200c[J].PLoS One,2017,12(2):e0172115.
[16]TSIAMBAS E,LEFAS A Y,GEORGIANNOS S N,et al.EG-FR gene deregulation mechanisms in lung adenocarcinoma.Amolecular review[J].Pathol Res Pract,2016,212(8):672-677.
[2]NAKAGAWA-SENDA H,YAMAGUCHI M,MATSUDA T,et al.Cancer prevalence in Aichi,Japan for 2012:Estimates based on incidence and survival data from population-based cancer registry[J].Asian Pac J Cancer Prev,2017,18(8):2151-2156.
[3]LIU C,ZHONG D L,BAI C,et al.Video-assisted thoracoscopic surgery and thoracotomy during lobectomy for clinical stage Inon-small-cell lung cancer have equivalent oncological outcomes:A single-center experience of 212 consecutive resections[J].Oncology Letters,2015,9(3):1364-1372.
[4]BUROTTO M,ALI S A,O′SULLIVAN C G.Class act:safety comparison of approved tyrosine kinase inhibitors for non-smallcell lung carcinoma[J].Expert Opin Drug Saf,2015,14(1):1-14.
[5]廖玉婷,周娟,张为民,等.表皮生长因子受体基因突变状态与晚期肺腺癌一线化疗疗效的关系[J].实用医学杂志,2018,34(7):1047-1050,1055.
[6]姚秀琴,徐韫健,付玉梅,等.非小细胞肺腺癌患者恶性胸水表皮生长因子受体基因突变的分析[J].实用医学杂志,2017,33(23):3980-3983.
[7]MARTIN P,SHIAU C J,PASIC M,et al.Clinical impact of mutation fraction in epidermal growth factor receptor mutation positive NSCLC patients[J].Br J Cancer,2016,114(6):616-622.
[8]MIRANDA O,FAROOQUI M,SIEGFRIED J M.Status of Agents Targeting the HGF/c-Met Axis in Lung Cancer[J].Cancers(Basel),2018,10(9).pii:E280.
[9]姚晓燕,申淑景,王晔,等.EGFR突变与非小细胞肺癌临床病理和TKI治疗疗效预测相关性分析[J].中华肿瘤防治杂志,2016,23(6):369-372.
[10]肖芸,罗辉,黄敏.表皮生长因子受体基因突变对非小细胞肺癌临床病理与酪氨酸激酶抑制剂疗效的影响[J].中国老年学,2017,37(23):5849-5851.
[11]王芬,王洁,白桦,等.晚期非小细胞肺癌EGFR蛋白磷酸化、基因突变与EGFR-TKI疗效相关性的研究[J].中国癌症杂志,2014,24(9):657-668.
[12]PARK I K,HYUN K,PARK S,et al.P3.16-013 prognostic effect of EGFR gene mutation for recurrence in completely resected lung adenocarcinoma[J].J Thoracic Oncol,2017,12(11):S2348.
[13]OSAWA M,OHASHI K,KUBO T,et al.Effect of vandetanib on lung tumorigenesis in transgenic mice carrying an activating Egfr gene mutation[J].Acta Medica Okayama,2016,70(4):243.
[14]HERNANDEZ M A,ALATORRE A J,GARIBAY J C,et al.LATE-BREAKING ABSTRACT:Treatment efficacy of afatinib vs gefitinib in lung adenocarcinoma with EGFR gene mutation[J].Eur Respira J,2016,48(suppl 60):PA2880.
[15]NARITA M,SHIMURA E,NAGASAWA A,et al.Chronic treatment of non-small-cell lung cancer cells with gefitinib leads to an epigenetic loss of epithelial properties associated with reductions in microRNA-155 and-200c[J].PLoS One,2017,12(2):e0172115.
[16]TSIAMBAS E,LEFAS A Y,GEORGIANNOS S N,et al.EG-FR gene deregulation mechanisms in lung adenocarcinoma.Amolecular review[J].Pathol Res Pract,2016,212(8):672-677.