Lung cancer (LC) is a lethal malignancy characterized by rapid progression, low survival outcomes and worse prognosis [1]. Non-small cell lung cancer (NSCLC) is the most common type of LC, accounting for over 80% of LC cases [2], [3]. Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the most common subtypes of NSCLC [4], [5], [6]. Recently, targeted therapy and immunotherapy have exerted crucial roles in preventing the growth of NSCLC cells and improving patients’ survival [7], [8], [9]. However, the current five-year survival rates of NSCLC patients remain unsatisfactory [10]. Thus, it is still an important challenge to uncover powerful indicators for predicting the prognosis of NSCLC patients, in order to make better individual therapeutic decisions and improve patient outcomes indirectly.

The immediate-early genes [e.g. Jun, Fos, c-myc, immediate-early response 2 (IER2), IER3 and IER5] exhibit crucial roles in regulating cancer cell growth, motility and metastasis [11], [12], [13], [14]. Numerous researches have shown the crucial functions of Jun, Fos, c-myc in cancer development [15], [16], [17]. Additionally, IER2, a member of the immediate-early response (IER) gene family, has been indicated to exert a tumor-promotive function in colorectal cancer [13]. Moreover, IER2 is able to contribute to the metastasis of hepatocellular carcinoma (HCC) cells through modulating MAPK and PI3K/Akt signaling pathways [18]. IER3, as known as IER gene X-1, is elevated in cancers, such as HCC and tongue cancer (TC) [14], [19], [20]. Downregulation of IER3 could repress TC cell migration and invasion [20]. IER5 has been recognized as a target gene of p53, and its level was transcriptionally elevated in cervical cancer [21]. IER5 could contribute to tumorigenesis via activation of heat shock factor 1 (HSF1) [21]. Furthermore, evidences have shown that IER2, IER3 and IER5 are all related to cancer prognosis [13], [14], [21], [22]. These findings demonstrate an important role of immediate-early response gene family in cancer progression.

Immediate early response 5 like (IER5L) is an another member of IER gene family [23]. A previous research has shown that IER5L mRNA level was elevated in colorectal cancer (CRC) tissues; high IER5L level might be related to worse prognosis in CRC patients [24]. Nevertheless, the role of IER5L in the prognosis of NSCLC remains largely unstudied, especially involving its association with tumor microenvironment. Thus, in current work, we aimed to investigate the role of IER5L in the prognosis of NSCLC. Our data are expected to give more insights into discovering novel prognostic markers for NSCLC.