Figure 3. Lung cancer patients with high DDR1 expression display decreased response to chemotherapy and metastasis-free survival.
(A) Kaplan-Meier metastasis-free survival estimates according to DDR1 levels in lung cancer patients subjected to chemotherapy. Data were obtained from www.kmplot.com/lung (28). (B) Clinical response of patients with stage II LUAD from the TCGA database harboring non-druggable oncogenic drivers. Results are plotted based on DDR1 levels (y axis) and indicated along the x axis as patients free of recurrence (n = 44) vs. recurrence (n = 15). Wilcoxon’s test was used to analyze statistical significance. *P < 0.05. (C) Crl:NU-Foxn1nu mice implanted with KRAS-mutant PDX were treated with either vehicle or standard chemotherapy based on cisplatin (3 mg/kg) and paclitaxel (20 mg/kg) administered i.p. every 5 days for 3 weeks (n = 6). After necropsy, tumor samples were fixed and analyzed for DDR1 expression by immunostaining. Clones showing high DDR1 expression are observed in the chemotherapy-treated tumors. Scale bar: 50 μm. (D) Differential DDR1 expression in chemoresistant tumor propagating cells (TPCs) vs. the tumor bulk population (non-TPC). Gene expression data was obtained from GSE46439 (29). Wilcoxon’s test P value is indicated above the box plots. (E and F) Samples from 6 patients with LUAD with lymph node metastasis were classified, following treatment, according to the persistence (nonresponders, n = 3) or absence (responders, n = 3) of the initial lymph node metastasis. Overall DDR1 expression and the activating phosphorylation (Y-792) were evaluated in these samples by qPCR (E) or by Western blot (F). GAPDH was used as loading control. High DDR1 expression shows significant association with poor clinical response. Data were analyzed using unpaired Student’s t test. *P < 0.05. Data are shown as the mean ± SEM.