Construction of inflammatory associated risk gene prognostic model of NSCLC and its correlation with chemotherapy sensitivity.

BACKGROUND: Inflammation is an important pathogenic factor of most malignant tumors. It is essential to understand mechanism underlying inflammation and cancer development, so as to formulate and develop anti-cancer treatment strategies. However, inflammatory-related gene characterization as well as risk model construction in prognosis and response chemotherapy or immunotherapy in NSCLC are still remain unclear. METHODS: A total of 1014 lung cancer samples with RNA-seqencing results were download from The Cancer Genome Atlas (TCGA) database. The patient cohort was randomized as a training and test cohorts, and 200 inflammatory-related genes were selected based on previously published data. Consensus clustering and Enrichment and immune function analyses base on Differential expression genes (DEGs) were performed. Prognosis Prediction Model were Constructed and Chemotherapy and immunotherapy sensitivity base on this model were performed. At last, H1299 and HCC827 cells were used to tested the mitoxantrone and oxal iplatin sensitivity after KRT6A knockdown. RESULTS: We identified the inflammatory-related genes from NSCLC datasets to build one prognosis prediction signature based on cluster inflammatory-related genes to lay a certain foundation for distinguishing high-risk NSCLC cases with dismal prognostic outcome. The nomogram provides the AUC values for 1-, 3-, and 5-year overall survival were 0.831, 0.853, and 0.86 in validation cohort. Morover, different sensitivity of immunotherapy or chemotherapy also were classified base on the different risk groups in NSCLC patients, which provided potent clinical reference. At last, targeting KRT6A sensitive to mitoxantrone and oxaliplatin in H1299 and HCC827 cells. CONCLUSIONS: Inflammatory-related gene risk-score is the potential chemotherapeutic and immunotherapeutic biomarker for NSCLC, and targeting KRT6A sensitive to mitoxantrone and oxaliplatin in NSCLC.HighlightsInflammatory-related genes can lay a certain foundation for distinguishing high-risk NSCLC cases with dismal prognostic outcome.Risk-score base on inflammatory-related genes is positive correlated with CD274, TGFBR1 and TGFB1 expression.Targeting KRT6A sensitive to mitoxantrone and oxaliplatin in H1299 and HCC827 cells.

The lncKLF6/KLF6 feedback loop regulates the growth of non-small cell lung cancer.

Non-small lung cancer (NSCLC) is one of the most common causes of cancer-associated death worldwide. Long noncoding RNAs (lncRNAs) regulate cancer initiation and progression through different mechanisms. In the present study, we characterized a novel lncRNA named lncKLF6, which was upregulated in NSCLC and associated with poor clinical outcomes. lncKLF6 inhibited Kruppel-like factor 6 (KLF6) transcription and then facilitated NSCLC growth. lncKLF6 is associated with the epigenetic repressor BMI1 and regulates its stability via recruiting deubiquitinase USP22. Moreover, it was revealed that lncKLF6 was a KLF6-responsive lncRNA, as KLF6 could occupy the lncKLF6 promoter to facilitate its transcription. The negative feedback loop of lncKLF6 and KLF6 continuously enhanced the oncogenic effects. Thus, our study elucidates the mechanism of lncKLF6-mediated growth via suppression of KLF6, which provides the promising target for developing new therapeutic strategy in NSCLC.