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  P59 - Tumor Biology and Systems Biology - Basic and Translational Science - Genomics (ID 197)

  • Event: WCLC 2020
  • Type: Posters
  • Track: Tumor Biology and Systems Biology - Basic and Translational Science
  • Presentations: 1
  • Moderators:
  • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall

  • 35784

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    P59.06 - Mutational Landscape and Differential Expression Analysis of Transcription Factors in Non-Small Cell Lung Cancer (ID 2018)

    00:00 - 00:00  |  Presenting Author(s): Youyu Wang
    • Abstract
    • Slides

    Introduction
    

    Mutational and expressional profiles of lung cancer have been widely studied. Many studies have demonstrated the important role of transcription factors (TFs) in tumorigenesis and development. However, the TF mutational and expressional profiles between the two common subtypes of non-small cell lung cancer (NSCLC), lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are yet to be systemically explored.

    Methods
    

    Somatic mutations and gene expression matrices of GDC TCGA LUAD (n=567) and LUSC (n=494) were downloaded from UCSC xena. List of human TFs was downloaded from AnimalTFDB. Fisher’s exact test was used to measure the TFs non-synonymous mutation frequency between LUAD and LUSC. Differential expression analysis was performed on 56 LUAD and 48 LUSC samples with paired-normal tissues, using DESeq2 and edgeR. The threshold for differentially expressed genes (DEGs) was set as fold change > 2 and FDR < 0.05.

    Results
    

    There were 73 TFs with significantly differential mutation frequency (P < 0.05), with 3 TFs only mutated in LUAD and 13 in LUSC (Fig.1A). We identified 373 differentially expressed TFs in LUAD, with 267 up-regulated and 106 down-regulated. 487 TFs were differentially expressed in LUSC, with 342 up-regulated and 155 down-regulated. 292 (50.5%) were overlapping between LUAD and LUSC, while 286 (49.5%) were specific to LUAD or LUSC (Fig.1B). There was no overlap in LUAD specifically mutated and up-regulated TFs. ASCL4 and ZNF385A were only mutated and up-regulated in LUSC. Previous studies have showed that ASCL4 is a critical driver of ferroptosis and ferroptosis inducers such as erastin and sorafenib can inhibit ferroptosis in liver cancer cells¹. Kaplan-Meier plot showed that ASCL4 expression level on LUSC patients had a significant effect on the patients’ survival (P = 0.028 by log rank test) (Fig.1E). The ZNF385A expression level of LUSC tumor was significantly higher (Fig.1D). Previous studies supported that the LUSC ZNF385A isoform model were different from LUAD, whose protein product interacted with TP53 and promoted growth arrest².

    

    Conclusion
    

    TFs mutational and expressional profiles are between LUAD and LUSC. ASCL4 and ZNF385A may be candidate biomarkers for LUSC and provide potential molecular targets for prognosis and therapy. References: [1] Xiaofang Sun, Zhanhui Ou, Ruochan Chen, etc. Hepatology 2016; 63:173-184; [2] Sanjeev Das, Lakshmi Raj, Bo Zhao, etc. Cell 2007; 130:624-637.

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