1. Age, SexHistologyPredominant subtype Pathological stage EGFR mutation CAF1 61, MaleAdenocarcinoma Solid predominant pT3N2M0 L858R CAF2 71, MaleAdenocarcinoma Lepidic predominant pT1bN0M0 Negative CAF3 63, FemaleAdenocarcinoma Acinar predominant pT2aN0M0 Negative CAF4 64, MaleAdenocarcinoma Papillary predominant pT2bN1M0 Exon 19 deletion CAF5 55, FemaleAdenocarcinoma Lepidic predominant pT1aN0M0 Exon 19 deletion CAF6 75, MaleAdenocarcinoma Lepidic predominant pT2aN0M0 L858R Supplemental Table 1. Characteristics of primary adenocarcinoma from which CAFs were obtained.

2. Characteristics Podoplanin expression of CAFs P-value Positive N (%) Negative N (%) Number of patients5749 Predominant Subtype Lepidic predominant Papillary predominant Acinar predominant Solid predominant 4 (7) 25 (44) 6 (11) 22 (39) 10 (21) 29 (59) 5 (10) <0.001* Pathological stage IA / IB IIA / IIB IIIA / IIIB IV 5 (9) / 11 (20) 10 (18) / 1 (2) 26 (44) / 3 (5) 1 (2) 8 (16) / 7 (14) 2 (4) / 1 (2) 23 (48) / 5 (10) 3 (6) 0.326** Lymphatic permeation Positive / Negative 21 (36) / 36 (64) 24 (49) /25 (51) 0.240 Vascular invasion Positive / Negative 45 (78) / 12 (22) 25(51) / 24 (49) 0.004 Pleural invasion Positive / Negative 25 (42) / 32 (58) 24 (50) / 25 (50) 0.696 Pulmonary metastases Positive / Negative 8 (15) / 49 (85) 15 (22) / 34 (78) 0.057 Supplemental Table 2. Primary tumor characteristics (N=106). * P-value for solid vs non-solid predominant subtype ** P-value for Stage I+II vs III+IV

3. Variables Univariate analysis P-value Multivariate analysis Hazard ratio95% C. I.P-value PDPN expression (positive)0.01041.9991.187-3.4160.009 Age (≥70)0.06820.6390.378-1.060.084 Gender (male)0.04191.6390.893-2.9900.110 Performance Status (≥2)<0.00119.4606.746-53.342<0.001 Smoking status (smoker)0.09551.1660.650-2.0950.606 Pathological stage (stage III,IV)0.21792.0481.042-4.0970.038 EGFR status (Minor mutation)0.18025.3091.524-14.2280.012 Adjuvant chemotherapy (YES)0.29871.0930.614-1.9200.760 Vascular invasion (positive)0.00171.4530.868-2.4500.245 Lymphatic permeation (positive)0.70080.9040.520-1.5470.714 Pleural invasion (positive)0.14421.4530.868-2.4500.112 Pulmonary metastases (positive)0.33131.1940.653-2.1380.557 Supplemental Table 3. Impact of predictive factors on progression free survival of EGFR-TKI in patients with EGFR activating mutation by univariate and multivariate analysis (n=106). PDPN, podoplanin; C. I., confidence interval

4. Supplemental Table 4. The correlation between PDPN expression status and clinical response to EGFR-TKIs in patients with EGFR common mutations, exon 19 deletion and L858R (N=102). (A) Overall response rate (ORR), (B) Median survival time (MST). EGFR mutation CAF PDPN(-) ORR(%) CAF PDPN(+) ORR(%) P-value L858R (N=56) 78% (N=21) 49% (N=35) 0.0532 Exon 19 deletion (N=46) 86% (N=27) 52% (N=19) 0.2095 EGFR mutation CAF PDPN(-) MST (months) CAF PDPN(+) MST (months) P-value L858R (N=56)17.212.80.1684 Exon 19 deletion (N=46)13.39.6 0.1144 (A) (B)