Objective:To explore the expression levels of aldehyde dehydrogenase 1 (ALDH1) and ATP-binding cassette superfamily G member 2 (ABCG2) in non-small cell lung cancer (NSCLC) tissues, and to observe the correlations of their expressions with clinicopathological features and prognosis of patients.Methods:The tissue samples from 82 patients with NSCLC who underwent surgical treatment from January 2016 to November 2018 in Taishan Hospital of Shandong Province were selected. The expressions of ALDH1 and ABCG2 in fresh cancer tissues and adjacent tissues were detected by immunohistochemistry. χ 2 test was used to analyze the correlations of ALDH1 and ABCG2 expressions with clinicopathological features of patients; Pearson method was used to analyze the correlation between ALDH1 and ABCG2; Kaplan-Meier method and log-rank test was used to analyze the correlations of ALDH1 and ABCG2 expressions with the overall survival (OS) of patients; Cox proportional hazards model was used to analyze the influencing factors of OS. Results:The positive expression rates of ALDH1 and ABCG2 in NSCLC tissues were higher than those in adjacent tissues, and the differences were statistically significant [60.98% (50/82) vs. 12.19% (10/82), 51.22% (42/82) vs. 3.66% (3/82), χ 2 values were 42.051 and 46.582, both P < 0.01]. ALDH1 expression was positively correlated with ABCG2 expression in NSCLC tissues (P < 0.05). The positive expression rates of ALDH1 and ABCG2 in patients with TNM stage Ⅱ-Ⅲ were higher than those in patients with stage Ⅰ [70.00% (35/50) vs. 46.88% (15/32), 60.00% (30/50) vs. 37.50% (12/32), both P < 0.05], and the positive expression rates of ALDH1 and ABCG2 in patients with lymph node metastasis were higher than those in patients without metastasis [75.00% (27/36) vs. 50.00% (23/46), 66.67% (24/36) vs. 39.13% (18/46), both P < 0.05]. The median follow-up time was 22.5 months, a total of 2 patients were lost to follow-up, and the median OS time was 25.4 months. The OS rate of ALDH1-positive patients was lower than that of ALDH1-negative patients (χ 2 = 5.124, P = 0.031), and the OS rate of ABCG2-positive patients was lower than that of ABCG2-negative patients (χ 2 = 6.969, P = 0.008). Multivariate Cox analysis showed that age (OR = 1.241, 95% CI 1.021-2.535, P = 0.045), lymph node metastasis (OR = 1.521, 95% CI 1.102-4.281, P = 0.012), TNM stage (OR = 2.104, 95% CI 1.289-6.150, P = 0.018), ALDH1 (OR = 2.435, 95% CI 1.214-8.654, P = 0.001), and ABCG2 (OR = 1.503, 95% CI 1.148-5.696, P = 0.021) were independent influencing factors of OS for patients with NSCLC. Conclusions:The expressions of ALDH1 and ABCG2 in NSCLC tissues are increased, and they are associated with lymph node metastasis and TNM staging. The OS rate in ALDH1-positive and ABCG2-positive patients is low. ALDH1 and ABCG2 may be prognostic markers for NSCLC.

Homeostasis ; Lysosomes/metabolism* ; Lipid Metabolism ; Glycosphingolipids/metabolism*

A change in the metabolic flux of glucose from mitochondrial oxidative phosphorylation (OXPHOS) to aerobic glycolysis is regarded as one hallmark of cancer. However, the mechanisms underlying the metabolic switch between aerobic glycolysis and OXPHOS are unclear. Here we show that the M2 isoform of pyruvate kinase (PKM2), one of the rate-limiting enzymes in glycolysis, interacts with mitofusin 2 (MFN2), a key regulator of mitochondrial fusion, to promote mitochondrial fusion and OXPHOS, and attenuate glycolysis. mTOR increases the PKM2:MFN2 interaction by phosphorylating MFN2 and thereby modulates the effect of PKM2:MFN2 on glycolysis, mitochondrial fusion and OXPHOS. Thus, an mTOR-MFN2-PKM2 signaling axis couples glycolysis and OXPHOS to modulate cancer cell growth.