Prognostic Value of Long Noncoding RNA DLEU2 and Its Relationship with Immune Infiltration in Kidney Renal Clear Cell Carcinoma and Liver Hepatocellular Carcinoma

Abstract

Background: DLEU2 is a long noncoding RNA considered important in the progression of many cancers. However, correlations between DLEU2 and kidney renal clear cell carcinoma (KIRC) and liver hepatocellular carcinoma (LIHC) have rarely been reported.

Methods: We first analysed the expression of DLEU2 across cancers and the correlation between DLEU2 and the clinical features of KIRC and LIHC by using the "ggplot2" package in R and searched the Oncomine database and Timer website platform. We verified the expression of DLEU2 in the GEO dataset (GSE105261 and GSE45267). Receiver operating characteristic (ROC) curves were drawn using the "pROC" and "ggplot2" packages in R, and we constructed a DLEU2-based prognostic nomogram for KIRC and LIHC by using the "survival" and "rms" packages in R. Then, we analysed the correlation between DLEU2 expression and prognosis in R as well as the correlation between DLEU2 and immune cell infiltration in the TIMER database. Finally, we explored the causes of DLEU2 upregulation in the UCSC Xena and UALCAN databases.

Results: We found that DLEU2 was upregulated in many cancers, including KIRC and LIHC. Expression of DLEU2 is associated with tumour stage, grade, lymphatic metastasis, and distant metastasis in KIRC as well as alpha-fetoprotein (AFP), tumour stage, grade, lymphatic metastasis, and distant metastasis in LIHC. DLEU2 is an adverse factor for the prognosis of KIRC and LIHC. In addition, DLEU2 has moderate accuracy in diagnosing KIRC and LIHC and predicting their prognosis. Moreover, we found that expression of DLEU2 correlated positively with immune cell infiltration in KIRC and LIHC, and upregulation of DLEU2 in KIRC and LIHC suggests a poor prognosis based on immune cells analysis. Genetic and epigenetic analyses of DLEU2 indicate that copy number variations (CNVs) and methylation contribute to the upregulation of DLEU2.

Conclusion: The long noncoding RNA DLEU2 has the potential to predict the prognosis and immune infiltration of KIRC and LIHC.

Keywords: DLEU2; KIRC; LIHC; immune infiltration; prognosis.

Figure 1

Expression of DLEU2 in cancer tissues and matched normal tissues in various cancers. (A) DLEU2 expression in cancer tissues and matched normal tissues in various cancers derived from the Oncomine database. (B) DLEU2 expression in different cancers derived from the TIMER website platform and the text in the red box refers to the expression level of DLEU2 in KIRC and LIHC. (C) Differences in DLEU2 expression between KIRC samples and matched normal samples. (D–F) The expression level of DLEU2 correlated significantly with the T stage (D), N stage (E) and M stage (F) in the international TNM staging system of KIRC. (G) Differences in DLEU2 expression between LIHC samples and matched normal samples. (H–J) Expression of DLEU2 correlated significantly with the T stage in the international TNM staging system of LIHC (H), histological grade (I) and AFP level (J). *p<0.05; **p<0.01; ***p<0.001.

Figure 2

ROC curve of DLEU2 expression predicting the outcome of KIRC (A) and LIHC (B).

Figure 3

DLEU2-based nomogram and calibration curve. (A) Nomogram of the 1-, 2-, and 3-year survival probabilities of OS in KIRC based on age, the T stage, M stage, histologic grade and DLEU2 expression level; (B) 1-year calibration curve in KIRC; (C) 2-year calibration curve in KIRC; (D) 3-year calibration curve in KIRC; (E) Nomogram of the 1-, 2-, and 3-year survival probabilities of OS in LIHC based on the histologic grade, tumour status and DLEU2 expression level; (F) 1-year calibration curve in LIHC; (G) 2-year calibration curve in LIHC; (H) 3-year calibration curve in LIHC.

Figure 4

Survival curves of high and low DLEU2 expression in different cancers derived from the Kaplan–Meier Plotter database. Among them, red text refers to DLEU2 high expression group, black refers to DLEU2 low expression group. (A) High expression of DLEU2 indicates a poor OS of KIRC. (B) High expression of DLEU2 is associated with a poor OS in LIHC. (C) High expression of DLEU2 correlates with a poor OS in UCEC. (D) High expression of DLEU2 implies a poor OS in KIRP.

Figure 5

Forest plot of the prognostic value of DLEU2 expression in different cancer types. In the forest plot, the text in the red box refers to the two cancers in this study, KIRC and LIHC, the red dot refers to the value of HR, and the green line represents the 95% CI. (A–C) Prognostic HR of DLEU2 in various cancers for OS (A), DSS (B), and PFI (C).

Figure 6

Correlation analyses between the DLEU2 expression level and the infiltrating immune cell level in KIRC (A) and LIHC (B). The red text “cor” and “p” refer to the correlation coefficient and statistical difference between DLEU2 and the level of immune cell infiltration respectively.

Figure 7

Kaplan–Meier survival curves of high and low DLEU2 expression based on the enrichment of different immune cells. Among them, red text refers to DLEU2 high expression group, black refers to DLEU2 low expression group. (A–H) High DLEU2 expression indicates a worse prognosis based on the enrichment of B cells (A), CD4+ memory T cells (B), CD8+ T cells (C), macrophages (D), NK T cells (E), Treg T cells (F), and Th1 cells (G) in KIRC. (I–P) High DLEU2 expression is associated with a poor prognosis based on the enrichment of various immune cells, such as B cells (I), CD4+ memory T cells (J), CD8+ T cells (K), macrophages (L), NK T cells (M), Treg T cells (N), Th1 cells (O) and Th2 cells (P).

Figure 8

Analysis of gene expression, CNVs, somatic mutations and methylation in KIRC and LIHC. Heat map displaying the correlations between DLEU2 expression and CNVs, somatic mutations, and methylation in KIRC (A) and LIHC (B).