Fig. 2: Panx1 contributes to genotoxic stress-induced IL-6 and has clinical relevance.

A, B Panx1 gene expression in A549 cells treated with increasing concentrations of (A) SA or (B) Dox for 24 h was measured by qRT-PCR. C Panx1 mRNA levels in primary human liposarcoma cell cultures were analyzed using the GSE12972 dataset and their log₂-transformed values were compared between control (n = 19) and paired Dox-treated (n = 19) cells. D, E Pearson’s correlation analysis of IL-6 and Panx1 gene expression in (D) primary human liposarcoma cell cultures or (E) lung adenocarcinomas using the (D) GSE12972 (n = 38) or (E) GSE68465 (n = 443) dataset, respectively. F Heatmap of Pearson’s correlation coefficients (r) between IL-6 and Panx1 or between IL-6 or Panx1 versus factors relevant to DNA damage repair (ATM, ATR, BRCA1, BRCA2, Chk1, and PRKDC), anti-apoptosis (Mcl-1), pro-apoptosis (Bad), EMT stimulation (Snail, Slug, Vimentin, N-cadherin, TWIST1, TWIST2, and MMP9), or EMT suppression (E-Cadherin, EPCAM, TJP3, and Occludin) in the TCGA LUNG cohort (n = 994). G qRT-PCR analysis of IL-6 gene expression in A549 cells untreated or treated with 20 µM SA or 0.5 µM Dox in the absence or presence of the Panx1 inhibitor CBX (50 µM) for 24 h. H The concentration of IL-6 present in the culture supernatants of A549 cells untreated or treated with 20 µM SA or 0.5 µM Dox in the absence or presence of 50 µM CBX for 24 h was determined by ELISA. I Panx1 mRNA levels in lung adenocarcinomas with different histological grades were investigated using the GSE68465 dataset and their log₂-transformed values were compared among well (n = 60), moderately (n = 209), and poorly (n = 167) differentiated tumors. J Kaplan–Meier analysis of the relationship between Panx1 gene expression and disease-free survival (DFS) in lung cancer patients from the GSE30219 cohort. K, L Kaplan-Meier analysis of the relationship between Panx1 gene expression and overall survival (OS) in cancer patients from The Cancer Genome Atlas (TCGA) (K) lung cancer (LUNG) or (L) Pan-Cancer datasets. Error bars represent mean ± SD, n = 3. Statistical analysis was performed using unpaired two-tailed Student’s t test (A, B), paired two-tailed Student’s t test (C), two-way ANOVA with Tukey’s multiple comparisons test (G, H), one-way ANOVA with Tukey’s multiple comparisons test (I), or log-rank test (J–L). *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001; ns not significant.