EGFR/TGF-α联合表达与动态血浆EBV DNA监测用于II期鼻咽癌预后分层：一项前瞻性队列研究
Combined EGFR/TGF-α Expression and Dynamic Plasma EBV DNA Monitoring for Prognostic Stratification in Stage II Nasopharyngeal Carcinoma: A Prospective Cohort Study.
文献信息
| PMID | 42946391 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Junping Liu |
| 作者单位 | Department of Otolaryngology Head Neck Surgery, Mindong Hospital, Fuan, Fujian, China. |
| 期刊 | Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery |
| SCI 分区 | Q2 |
| IF | 2 |
| 研究类型 | 临床研究 · 临床 |
| 所属专科 | 鼻咽癌 |
中文摘要
背景： 在解剖学上同质的II期鼻咽癌（NPC）中，风险分层仍不精确。我们将连续血浆EB病毒（EBV）DNA监测与治疗前EGFR/TGF-α免疫组化相结合，以评估其联合预后价值。
方法： 66例前瞻性入组的II期（T2N0M0）NPC患者接受以顺铂为基础的同步放化疗（IMRT或VMAT，66-70 Gy）。在基线和预设监测间隔（前2年每2-3个月一次，之后每6个月一次）于5年随访期间定量血浆EBV DNA。EGFR和TGF-α按四级IHC量表分级（++/+++ = 阳性）。预设了一个简约多变量Cox模型，包含三个生物学预设协变量（EGFR、TGF-α、治疗后EBV异常状态）以及一个探索性EGFR × TGF-α交互作用；构建了复合三级风险评分（0/1/≥ 2个不良生物标志物）。
结果： 中位潜在随访时间（反向Kaplan-Meier法）为58.6个月。EGFR阳性率为60.6%，TGF-α阳性率为53.0%，治疗前EBV DNA可检出率为87.9%。在所有6例发生临床复发并接受连续监测的患者中，血浆EBV-DNA在影像学复发前中位3.2个月（范围1.4-5.8）越过500 copies/mL检测阈值。治疗后EBV异常动力学（aHR 3.85，95% CI：1.60-9.27；p = 0.003）和EGFR阳性（aHR 2.58，1.08-6.16；p = 0.033）是独立的不良OS预后因素；TGF-α显示非显著趋势（aHR 1.98；p = 0.124）。三级复合评分可区分5年OS：100%（低危，n = 11）、69.2%（中危，n = 26）和26.4%（高危，n = 29；中位OS 28.4个月；总体log-rank p < 0.001）。
结论： 整合EGFR/TGF-α表达与治疗后EBV DNA动力学的简约三生物标志物风险评分，在II期NPC中提供了高度区分性的预后分层，可识别适合治疗强化和降阶梯治疗的候选者。有必要进行外部验证。
英文摘要
BACKGROUND: Risk stratification within anatomically homogeneous stage II nasopharyngeal carcinoma (NPC) remains imprecise. We integrated serial plasma Epstein-Barr virus (EBV) DNA monitoring with pretreatment EGFR/TGF-α immunohistochemistry to evaluate their combined prognostic value.
METHODS: Sixty-six prospectively enrolled stage II (T2N0M0) NPC patients received cisplatin-based concurrent chemoradiotherapy (IMRT or VMAT, 66-70 Gy). Plasma EBV DNA was quantified at baseline and at prespecified surveillance intervals (every 2-3 months for the first 2 years, then every 6 months) during 5-year follow-up. EGFR and TGF-α were graded on a four-tier IHC scale (++/+++ = positive). A parsimonious multivariable Cox model with three biologically prespecified covariates (EGFR, TGF-α, post-treatment EBV-abnormal status) and an exploratory EGFR × TGF-α interaction were prespecified; a composite three-tier risk score (0/1/≥ 2 adverse biomarkers) was constructed.
RESULTS: Median potential follow-up (reverse Kaplan-Meier) was 58.6 months. EGFR was positive in 60.6%, TGF-α in 53.0%, and pretreatment EBV DNA detectable in 87.9%. Plasma EBV-DNA crossed the 500 copies/mL detection threshold a median of 3.2 months (range, 1.4-5.8) prior to radiologic recurrence in all six serially monitored patients who developed clinical recurrence. Post-treatment EBV-abnormal kinetics (aHR 3.85, 95% CI: 1.60-9.27; p = 0.003) and EGFR positivity (aHR 2.58, 1.08-6.16; p = 0.033) were independent adverse OS prognostic factors; TGF-α showed a non-significant trend (aHR 1.98; p = 0.124). The three-tier composite score discriminated 5-year OS at 100% (low-risk, n = 11), 69.2% (intermediate, n = 26), and 26.4% (high-risk, n = 29; median OS 28.4 months; overall log-rank p < 0.001).
CONCLUSION: A parsimonious three-biomarker risk score integrating EGFR/TGF-α expression and post-treatment EBV DNA kinetics provides highly discriminative prognostic stratification in stage II NPC, identifying candidates for both treatment intensification and de-intensification. External validation is warranted.