To better define the contribution of WEE1 rs3910384 to the efficacy of platinum-based chemotherapy, we performed a subgroup analysis stratified on different standard chemotherapy regimens and found that the rs3910384 genotype predominantly contributed towards the efficiency of platinum-gemcitabine regimen, which consists of two DNA- damaging agents, but contributed little to the efficacy of the other doublet regimens (tubulin-targeting agents or DNA topoisomerase inhibitors) used in the study (Fig. 1B–D; Table S5). The patients with WEE1 rs3910384 G/G homozygote gained 32.2% (from 22.1% to 54.3%), 24.1% (from 14.7% to 38.8%) or 20.3% (from 7.4% to 27.7%) absolute increase in 1-, 2-, and 3-year-survival rates, respectively, compared to the A/A+A/G genotype (p = 3.5E-4) (Table S6). Subgroup multivariate Cox regression analysis revealed that WEE1 rs3910384 dominate model and histology are independent factors for the OS of the 152 patients who received platinum-gemcitabine regimen (Table 3). The patients with G/G homozygote (mOS, 28.2; 95%CI, 20.5–35.9) had 13.5 months longer OS than A/A+A/G genotype (median OS, 14.7; 95%CI, 12.8–16.6; p = 6.9E-5). Adenocarcinoma patients were more sensitive than the squamous carcinoma, adenosquamous carcinoma, or other histological types when treated with platinum-gemcitabine regimen (p = 0.037). When evaluated with PFS as endpoint, a similar association in platinum-gemcitabine group was also observed, but not in the other platinum-based combination regimens (Fig. 2, Table S7).