KIAA1522 is a novel prognostic biomarker in patients with non-small cell lung cancer.

Yi-Zhen Liu,Jia-Jie Hao,Hai Yang,Xin Xu,Yan Cai,Jian Cao,Yan-Yi Jiang,Ming-Rong Wang

doi:10.1038/srep24786

Abstract

Nowadays, no robust biomarkers have been applied to clinical practice to provide prognostic evaluation of non-small cell lung cancer (NSCLC). This study aims to identify new potential prognostic biomarkers for NSCLC. In the present work, KIAA1522 is screened out from two independent GEO datasets as aberrantly up-regulated gene in NSCLC tissues. We evaluate KIAA1522 expression immunohistochemically in 583 NSCLC tissue samples and paired non-tumor tissues. KIAA1522 displays stronger staining in NSCLC cases than in adjacent normal lung tissues. Importantly, patients with KIAA1522 overexpression had a significantly shorter overall survival compared to those with low expression (P < 0.00001). Multivariate Cox regression analyses show that KIAA1522 is an independent prognostic indicator, even for early-stage NSCLCs (P = 0.00025, HR = 2.317, 95%CI: 1.477–3.635). We also found that high expression of KIAA1522 is a significant risk factor for decreased overall survival of the patients who received platinum-based chemotherapy. Gene set enrichment analysis (GSEA) and functional studies reveal that KIAA1522 is associated with oncogenic KRAS pathways. Taken together, high expression of KIAA1522 can be used as an independent biomarker for predication of poor survival and platinum-resistance of NSCLC patients, and aberrant KIAA1522 might be a new target for the therapy of the disease.

Highlights

IntroductionThe average value of log[2] (Tumor/Non-tumor) was calculated and shown in the rank order
After screening the association of KIAA1522 expression with the oncogenic signatures within the “c6.all.v5.0.” gene sets from MSigDB database[17], the results revealed that high KIAA1522 expression was associated with the hyper-activation of KRAS signatures in three datasets (Fig. 6A–C) and the activation of MEK signaling which is a down-stream factor of KRAS (Fig. 6D), suggesting the involvement of KIAA1522 in KRAS pathways
The results showed that knockdown of KIAA1522 expression (Fig. 6E) in A549 and H460 cell lines down-regulated the mRNA levels of the oncogenic KRAS (Fig. 6F)

Summary

Introduction

The average value of log[2] (Tumor/Non-tumor) was calculated and shown in the rank order. (D–F) Transcript levels of KIAA1522 in non-tumor tissues and NSCLC tissues from GSE19804 (D), GSE32863 (E) and GSE19188 (F) datasets. The examination of KIAA1522 following screened out by our approach in the tumor tissue samples may extend the range of utility of this protein as a biomarker in lung cancer patients. We show that the gene of KIAA1522 is aberrantly high expression in the NSCLC tissues and functions as a prognostic biomarkers indicating poor survival of NSCLC patients

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Conclusion