LUM Expression and Its Prognostic Significance in Gastric Cancer

Xiaowei Chen; Xin Li; Xueju Hu; Fei Jiang; Yan Shen; Rui Xu; Leilei Wu; Pingmin Wei; Xiaobing Shen

doi:10.3389/fonc.2020.00605

LUM Expression and Its Prognostic Significance in Gastric Cancer

Front Oncol. 2020 May 15:10:605. doi: 10.3389/fonc.2020.00605. eCollection 2020.

Authors

Xiaowei Chen^{1

2}, Xin Li¹, Xueju Hu¹, Fei Jiang^{1

2}, Yan Shen², Rui Xu¹, Leilei Wu¹, Pingmin Wei^{1

2}, Xiaobing Shen^{1

2}

Affiliations

¹ Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
² Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, China.

Abstract

Background: Lumican (LUM) is a member of the small leucine-rich proteoglycan family and plays dual roles as an oncogene and a tumor suppressor gene. The effect of LUM on tumors is still controversial. Methods: Gene expression profiles and clinical data of gastric cancer (GC) were downloaded from The Cancer Genome Atlas (TCGA) database. The expression difference of LUM in GC tissues and adjacent nontumor tissues was analyzed by R software and verified by quantitative real-time polymerase chain reaction (qRT-PCR) and comprehensive meta-analysis. The relationship between LUM expression and clinicopathological parameters was assessed by chi-square test and logistic regression. Kaplan-Meier survival analysis and Cox proportional hazards regression model were chosen to assess the effect of LUM expression on survival. Gene set enrichment analysis (GSEA) was used to screen the signaling pathways involved in GC between the low and the high LUM expression datasets. Results: The expression of LUM in GC tissues was significantly higher than that in adjacent nontumor tissues (P < 0.001) from the TCGA database. qRT-PCR (P = 0.022) and comprehensive meta-analysis (standard mean difference = 0.90, 95% CI: 0.34-1.46) demonstrated that LUM was upregulated in GC. The chi-square test showed that the high expression of LUM was correlated with tumor differentiation (P = 0.024) and T stage (P = 0.004). Logistic regression analysis showed that high LUM expression was significantly correlated with tumor differentiation (OR = 1.543 for poor vs. well or moderate, P = 0.043), pathological stage (OR = 3.149 for stage II vs. stage I, P = 0.001; OR = 2.505 for stage III vs. stage I, P = 0.007), and T classification (OR = 13.304 for T2 vs. T1, P = 0.014; OR = 18.434 for T3 vs. T1, P = 0.005; OR = 30.649 for T4 vs. T1, P = 0.001). The Kaplan-Meier curves suggested that patients with high LUM expression had a poor prognosis. Multivariate analysis showed that a high expression of LUM was an important independent predictor of poor overall survival (HR, 1.189; 95% CI, 1.011-1.400; P = 0.037). GSEA indicated that 14 signaling pathways were evidently enriched in samples with the high-LUM expression phenotype. Conclusions: LUM might act as an oncogene in the progression of GC and could be regarded as a potential prognostic indicator and therapeutic target for GC.

Keywords: GSEA; LUM; TCGA; gastric cancer; lumican; prognosis.