We thank Uramoto and Tanaka for their comments on our study. We think there are a few potential reasons for the discrepancy between their results and ours.
First, the study population differed. Lung adenocarcinoma in nonsmoking Asian females has been found to be a unique entity in that it has a higher frequency of activating epidermal growth factor (EGFR) mutation and better prognosis. Our study further showed that 70% of subjects had activated EGFR mutation, and the remaining 30% had anaplastic lymphoma kinase (ALK) fusion.[1, 3] Similarly, the different demographic characteristics in our study might also result in a different TS expression level. In addition, our selected population eliminated the impact of sex on TS expression, since TS expression differed between male and female subjects.
Second, as Uramoto and Tanaka mention, disparities in sampling species (messenger RNA vs protein level) and experimental methods (real-time polymerase chain reaction vs immunohistochemistry) might have led to different results.
Most importantly, the comparative population differed. We found that TS expression was significantly lower in patients with EGFR mutation than in those with both EGFR wild type and negative ALK fusion status. Uramoto and Tanaka compared TS expression in patients with EGFR mutation with patients who had EGFR wild-type. As we know, the EGFR wild-type group is heterogeneous, including the ALK fusion subgroup, which is not only associated with lower TS expression but also makes up a substantially large part of the wild-type group. As a result, Uramoto and Tanaka would be more likely to see a negative result.
However, because Chinese and Japanese patients have a similar mutation spectrum and a similar therapeutic efficacy, ethnic difference would contribute little to the discrepancy. Hopefully, the worldwide multiplex mutation driver examination and pharmacogenomics detection efforts currently underway will shed light on the relationship between EGFR mutation and TS expression in the future.