Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Thorac Cancer. 2024 Apr;15(10):788-796. doi: 10.1111/1759-7714.15268. Epub 2024 Feb 24.
It is difficult to predict gene mutations individually based on clinical background alone. Tumor markers may help to predict each gene mutation. Identifying tumor markers that can predict gene mutation will facilitate timely genetic testing and intervention.
We selected 134 cases of advanced or recurrent ALK-positive and 172 cases of advanced or recurrent EGFR-positive lung cancer from our clinical database. The cutoff values for the tumor markers were defined as 5.0 ng/mL or higher for carcinoembryonic antigen (CEA) and 3.5 ng/mL or higher for soluble fragment of cytokeratin 19 (CYFRA21-1) in accordance with the institutional standards. A positive CYFRA21-1:CEA ratio was defined as 0.7 or higher.
The CEA-positivity rate was 49% for ALK-positive lung cancers and 73% for EGFR-positive lung cancers, which was significantly different (p < 0.001). The CYFRA21-1 positivity rate was significantly higher in ALK-positive lung cancer (36%) compared with EGFR-positive lung cancer (23%) (p = 0.034). The median CYFRA21-1:CEA ratio was 0.395 for the ALK group, which was significantly higher compared with 0.098 for the EGFR group (p < 0.001). These trends were similar when excluding histology other than adenocarcinoma. The median time-to-treatment failure (TTF) for initial tyrosine kinase inhibitor (TKI) therapy was 308 days for the high CYFRA21-1:CEA ratio group and 617 days for the low CYFRA21-1:CEA ratio group for ALK-positive lung cancer (p = 0.100).
A higher proportion of patients with ALK-positive lung cancer were CYFRA21-1 positive and had higher CYFRA21-1:CEA ratios compared with EGFR-positive lung cancer patients.
仅根据临床背景预测基因突变较为困难。肿瘤标志物可能有助于预测每个基因突变。确定可预测基因突变的肿瘤标志物将有助于及时进行基因检测和干预。
我们从临床数据库中选择了 134 例晚期或复发性 ALK 阳性和 172 例晚期或复发性 EGFR 阳性肺癌患者。根据机构标准,将肿瘤标志物的截断值定义为癌胚抗原(CEA)高于 5.0ng/ml 或可溶性细胞角蛋白 19 片段(CYFRA21-1)高于 3.5ng/ml。将 CYFRA21-1:CEA 比值定义为 0.7 或更高。
ALK 阳性肺癌的 CEA 阳性率为 49%,EGFR 阳性肺癌的 CEA 阳性率为 73%,差异有统计学意义(p<0.001)。ALK 阳性肺癌的 CYFRA21-1 阳性率(36%)明显高于 EGFR 阳性肺癌(23%)(p=0.034)。ALK 组的中位 CYFRA21-1:CEA 比值为 0.395,明显高于 EGFR 组的 0.098(p<0.001)。当排除非腺癌组织学后,这些趋势相似。ALK 阳性肺癌中高 CYFRA21-1:CEA 比值组初始酪氨酸激酶抑制剂(TKI)治疗的中位无进展生存期(TTF)为 308 天,低 CYFRA21-1:CEA 比值组为 617 天(p=0.100)。
ALK 阳性肺癌患者中,CYFRA21-1 阳性患者的比例较高,且与 EGFR 阳性肺癌患者相比,CYFRA21-1:CEA 比值较高。