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. 2020 Dec 10:7:599110.
doi: 10.3389/fmolb.2020.599110. eCollection 2020.

KLHL5 Is a Prognostic-Related Biomarker and Correlated With Immune Infiltrates in Gastric Cancer

Qiulin Wu  1 , Guobing Yin  2 , Jinwei Lei  1 , Jiao Tian  1 , Ailin Lan  1 , Shengchun Liu  1
Affiliations

KLHL5 Is a Prognostic-Related Biomarker and Correlated With Immune Infiltrates in Gastric Cancer

Qiulin Wu et al. Front Mol Biosci. .

Abstract

Background: KLHL5 (Kelch Like Family Member 5) is differentially expressed in gastric cancer, but its correlation with prognosis and functioning mechanism in gastric cancer remain unclear. Methods: The Oncomine database and TIMER were employed to appraise the KLHL5 expression in a variety of cancers. The correlation between KLHL5 expression and patient prognosis was extracted from the Kaplan-Meier plotter, GEPIA, and PrognoScan database. Then the relationship between KLHL5 expression and inflammatory infiltrate profiles was inquired by TIMER. Finally, GEPIA and TIMER were explored for the correlative significance between KLHL5 expression and immune cell-related marker sets. Results: KLHL5 was found to be differentially expressed and correlated with clinical outcomes in several types of cancers in the TCGA database. Especially, KLHL5 mRNA expression was upregulated and correlated with poorer overall survival and progression-free survival in gastric cancer. Moreover, elevated KLHL5 expression was significantly related with patient node stage, infiltration level, and expression of multiple immune marker sets. Conclusions: These results implicate that KLHL5 expression is closely linked with patient clinical outcomes and the microenvironmental infiltration level in different neoplasms. This indicates that KLHL5 is a modulator in infiltrate recruitment, shaping the landscape of immune cell infiltration. Thus, it represents an eligible prognostic predictor for gastric malignancy.

Keywords: KLHL5; gastric cancer; immune infiltration; markers; prognosis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Full landscape of KLHL5 expression in different malignancies. (A) Differentially expressed KLHL5 in cancer tissues and normal controls in Oncomine database. (B) KLHL5 expression profile in multiple cancer types in TIMER database. *p < 0.05, **p < 0.01, and ***p < 0.001.
Figure 2
Figure 2
Correlations between KLHL5 and prognosis in different cancers. (A,B) Survival curves of DFS and RFS in two breast cancer cohorts. (C–H) KLHL5 expression is correlated with DFS in breast cancer (C), OS in brain glioma (D), DFS in colorectal cancer (E), OS in lung cancer (F), OS in ovarian cancer (G), and OS in blood cancer (H). (I–P) OS and PFS survival curves of gastric (I,J), lung (K,L), breast (M,N), and ovarian cancer (O,P).
Figure 3
Figure 3
Correlation between KLHL5 expression and inflammatory infiltration in CHOL and STAD. (A) KLHL5 is not correlated with tumor purity, B, CD8+ T, CD4+ T, macrophage, or dendritic cell infiltration in CHOL. It has a weak correlation with the level of neutrophil. (B) KLHL5 expression is associated with tumor purity and the infiltration of B, CD8+ T, CD4+ T, macrophage, neutrophil, and dendritic cells in STAD. (C) Kaplan–Meier curves of immune cell infiltration and KLHL5 expression in CHOL. (D) Kaplan–Meier curves of immune cell infiltration and KLHL5 expression in SATD.
Figure 4
Figure 4
Correlation between KLHL5 and immunocyte marker sets in CHOL and STAD. (A–D) The association between KLHL5 and gene markers of monocytes (A), TAMs (B), and M1 (C) and M2 macrophages (D) in CHOL. (E–H) Scatterplots of correlation between KLHL5 and gene markers of monocytes (E), TAMs (F), and M1 (G) and M2 macrophages (H) in STAD.
Figure 5
Figure 5
The differential expression of CD3D (A), CD3E (B), CD2 (C), CD79A (D), CD19 (E), HLA-DPB1 (F), HLA-DQB1 (G), HLA-DRA (H), CD86 (I), and CSF1R (J) in gastric cancer.
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