Lower SLC7A2 expression is associated with enhanced multidrug resistance, less immune infiltrates and worse prognosis of NSCLC

Abstract

Background Solute carrier family 7 member 2 (SLC7A2), a cationic amino acid transporter, is lowly expressed in ovarian and hepatocellular cancers, which is associated with their worse prognosis. However, its roles in the prognosis, drug resistance and immune infiltration in non-small-cell lung cancer (NSCLC) are unclear. Methods We chose SLC7A2 from RNA-Seq of paclitaxel/cisplatin-resistant A549 cells, then bioinformatics, cell lines construction, RT-qPCR, and CCK8 were performed to investigate SLC7A2 role. Result We analyzed the 223 differentially expressed genes (DEGs) from RNA-Seq of paclitaxel/cisplatin-resistant A549 cells and found that SLC7A2 expression was down-regulated in NSCLC. Lower SLC7A2 expression was associated with worse recurrence-free survival (RFS) in NSCLC. SLC7A2 silencing enhanced the proliferation of NSCLC cells and their insensitivity to paclitaxel, cisplatin, and gemcitabine in vitro. Activation of AMPK has up-regulated SLC7A2 expression and enhanced the sensitivity of NSCLC cells to anti-tumor drugs, which could be attributed to E2F1’s regulation. In addition, the levels of SLC7A2 expression were correlated to the numbers of infiltrated neutrophils, macrophages, dendritic cells and their marker genes, like CD86, HLA-DPA1 and ITGAM. Conclusions SLC7A2 may act as a tumor suppressor to modulate drug sensitivity, immune infiltration and survival in NSCLC.

SLC7A8 overexpression inhibits the growth and metastasis of lung adenocarcinoma and is correlated with a dismal prognosis

“…When overexpressed, it behaved like a tumor suppressor, especially in low-growth ER-positive subtypes [ 6 ]. Jiang et al found that SLC7A2 increased drug sensitivity, immune infiltration, and survival in NSCLC [ 12 ]. The upregulation of SLC7A7 increased the levels of arginine in tumor cells, thus promoting their migration and invasion [ 13 ].…”

“…Studies have identified some genes associated with cancer progression. SLC7 genes were reported to be correlated with the prognosis of lung cancer [11][12][13][14]. SLC7A5 was overexpressed in LUAD and significantly correlated with the Ki-67 labeling index, which can increase metabolic activity and is associated with tumor cell growth [11].…”

Amino acid transporters within the solute carrier superfamily: Underappreciated proteins and novel opportunities for cancer therapy

“…In addition, it was demonstrated that AMPK augments SLC7A2 expression to increase the sensitivity of cancer cells to anti-cancer drugs. More importantly, SLC7A2 modulates immune infiltration and correlates to the infiltrated neutrophils, macrophages, dendritic cells, and their markers such as CD86, HLA-DPA1, and ITGAM [ 93 ]. The protecting role of SLC7A2 from colitis-associated carcinogenesis in the setting of chronic colitis was proved in a study.…”