目的 探讨表皮生长因子受体（EGFR）突变肺腺癌间质纤维化程度与靶向治疗耐药及预后的相关性。 方法 选取2021年1月至2022年12月在医院接受治疗的207例EGFR突变中晚期肺腺癌患者的病历资料，根据患者的预后生存期，最终纳入86例。依据患者靶向治疗1年期间是否发生靶向治疗耐药分为耐药组32例和非耐药组54例，按照纤维化程度分为轻度纤维化、中度纤维化及重度纤维化，比较耐药组与非耐药患者的临床病理资料及纤维化程度，分析EGFR突变肺腺癌患者靶向治疗耐药的影响因素，随访记录不同纤维化程度患者的生存预后。 结果 耐药组EGFR外显子20 Ins突变、CA125、中重度纤维化占比高于非耐药组（P < 0.05）。多因素logistic回归分析得出，EGFR外显子20 Ins突变（OR = 3.691，95%CI：1.043 ~ 13.057）、CA125（OR = 4.104，95%CI：1.160 ~ 14.517）、中重度纤维化（OR = 3.959，95%CI：1.410 ~ 11.115）是EGFR突变肺腺癌患者靶向治疗耐药的危险因素（P < 0.05）。Cox基础模型显示，C-index = 0.72（95%CI：0.65 ~ 0.79），1年、2年生存预测AUC分别为0.781和0.734。EGFR外显子20Ins突变（HR = 3.691）、中重度纤维化（HR = 3.959）和CA125升高（HR = 4.104）是EGFR突变肺腺癌患者靶向治疗死亡的独立危险因素。轻度纤维化、中度纤维化、重度纤维化肺腺癌患者的中位PFS分别为10.5个月、7.2个月、3.9个月，中位OS分别为21.4个月、16.1个月、11.5个月，三组PFS曲线、OS曲线比较，差异有统计学意义（P < 0.05）。 结论 EGFR突变肺腺癌间质纤维化程度可影响靶向治疗耐药，且纤维化进展与不良预后有关。

Objective To assess stromal fibrosis in epidermal growth factor receptor （EGFR） mutant lung adenocarcinoma and its association with resistance to targeted therapy and patient prognosis. Methods Medical records of 207 patients diagnosed with EGFR-mutant advanced lung adenocarcinoma who received treatment at a hospital between January 2021 and December 2022 were reviewed. A total of 86 patients were ultimately included based on their prognosis and survival duration. These patients were categorized into a resistance group （32 cases） and a non-resistance group （54 cases）， depending on whether they developed resistance to targeted therapy within one year. Additionally， patients were classified into mild， moderate， and severe fibrosis groups according to the extent of fibrosis observed. Clinical and pathological characteristics， as well as fibrosis levels， were compared between the two groups. Factors influencing the development of resistance to targeted therapy in patients with EGFR-mutant lung adenocarcinoma were analyzed， and the survival outcomes of patients with varying degrees of fibrosis were evaluated during follow-up. Results In the resistance group， the prevalence of EGFR exon 20 insertion mutations， elevated CA125 levels， and the presence of moderate-to-severe fibrosis were significantly higher compared to the non-resistance group （P < 0.05）. Multivariate logistic regression analysis revealed that EGFR exon 20 insertion mutation （OR = 3.691， 95%CI： 1.043 ~ 13.057）， elevated CA125 levels （OR = 4.104， 95%CI： 1.160 ~ 14.517）， and moderate-to-severe fibrosis （OR = 3.959， 95%CI： 1.410 ~ 11.115） were independent risk factors associated with resistance to targeted therapy among patients with EGFR-mutant lung adenocarcinoma （P < 0.05）. The Cox proportional hazards model demonstrated a C-index of 0.72 （95%CI： 0.65 ~ 0.79）， with area under the curve （AUC） values for 1-year and 2-year survival predictions of 0.781 and 0.734， respectively. EGFR exon 20 insertion mutation （HR = 3.691）， moderate-to-severe fibrosis （HR = 3.959）， and elevated CA125 levels （HR = 4.104） were identified as independent prognostic factors for overall survival in these patients following targeted therapy. The median progression-free survival （PFS） for patients with mild， moderate， and severe fibrosis was 10.5 months， 7.2 months， and 3.9 months， respectively， while the median overall survival （OS） was 21.4 months， 16.1 months， and 11.5 months， respectively. Statistically significant differences in both PFS and OS were observed across the three fibrosis severity groups. （P < 0.05）. Conclusion The extent of stromal fibrosis in EGFR-mutant lung adenocarcinoma influences resistance to targeted therapy， and the progression of fibrosis is correlated with an unfavorable prognosis.