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.
Highlights
Gastric cancer is the leading drive of cancer-related mortality in humans, and poor prognosis of this disease is partly attributed to metastasis (Siegel et al, 2017)
The Oncomine was explored for illustrating the full landscape of KLHL5 in different malignant and adjacent benign tissues, and it revealed that KLHL5 was upregulated in mammary, cervical, head and neck, brain, colorectal, esophageal, lymphoma, and gastric cancer tissues in comparison with their normal controls (Figure 1A)
Complete profile of KLHL5 expression in different tumors is collated in Supplementary Table 1
Summary
Gastric cancer is the leading drive of cancer-related mortality in humans, and poor prognosis of this disease is partly attributed to metastasis (Siegel et al, 2017). The Kelch-like (KLHL) gene family is a group of evolutionarily conserved genes encoding proteins containing BTB domains and Kelch motifs (Dhanoa et al, 2013). Within these structures, the BTB takes part in recruitment degradation substrates to E3 ubiquitin ligase complexes by working as a bridge between the target recognition protein and the scaffold protein Cullin-3 (CUL3) (Perez-Torrado et al, 2006), and the Kelch motif is associated with actin kinetics by forming different types of binding sites (Adams et al, 2000). 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
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