Fig. 6: Elevated MT-CO2 expression is linked to oncogenic Ras and is positively correlated with the expression of c-JUN and GLS1, and with poor clinical outcomes in human lung cancer.

a–d Human lung cancer tissue microarrays consisting of 27 pairs of tumors and adjacent tissues were subjected to immunohistochemistry analyses for MT-CO2 and GLS1 expression (a) with quantitative analyses using average optical density (AOD) (b, c). The Pearson correlation between MT-CO2 and GLS1 in protein levels was analyzed (d). Scale bar, 200 μm. e–g Human lung tumor specimens harboring wild-type KRAS alleles (KRASWT, n = 11) or a KRAS mutant allele (KRASMT, n = 11) were qPCR analyzed for MT-CO2 (e), GLS1(f), and c-JUN (g) mRNA levels. h–j Human lung tumor samples (n = 23) were qPCR analyzed for MT-CO2, GLS1, and c-JUN mRNA levels. The Pearson correlation between MT-CO2 and GLS1 (h) or c-JUN (i) in mRNA levels was analyzed. The correlation between MT-CO2 mRNA levels and the overall survival (OS) in lung cancer patients was analyzed (j). k The correlation between GLS1 mRNA levels and overall survival (OS) in lung cancer patients was analyzed using the Kaplan–Meier Plotter database. Data were presented as mean ± SEM (b, c, e, f, g). Statistical analyses were performed with unpaired two-tailed Student’s t test (b, c, e, f, g), Log-rank (Mantel–Cox) test (j, k), and two-tailed Pearson correlation analysis (d, h, i).