Integrative Multi-Omics Analysis of Identified SKA3 as a Candidate Oncogene Correlates with Poor Prognosis and Immune Infiltration in Lung Adenocarcinoma

Abstract

Background Spindle and kinetochore-associated complex subunit 3 (SKA3) plays important roles in promoting the migration and the invasion of various human cancer cells. There are a few studies on SKA3 in lung adenocarcinoma (LUAD), but the in-depth analysis of the expression of SKA3 and the correlated possible immune mechanism of SKA3 in LUAD are not clear. Methods In our study, the expression and survival data of SKA3 were analyzed in LUAD using TIMER, Oncomine, UALCAN, cBioPortal, LinkedOmics, Human Protein Atlas, and Kaplan–Meier plotter. Then, quantitative PCR was used to verify the expression differences of SKA3 between LUAD tissues of mice and the normal tissues. Results We established that the expression of SKA3 in the LUAD group was remarkably higher than that in the normal group. Additionally, high SKA3 expression was linked to poorer survival in LUAD. Moreover, SKA3 expression had a remarkable negative correlation with the immune infiltration of B cells, macrophages, and CD4+ T cells. SKA3 was markedly negatively related to the immune type biomarkers of T cells and B cells in LUAD. The elevated expression of SKA3 with LUAD in enriched B cells, CD4+ T cells, CD8+ T cells, macrophages and Treg cells had worse prognosis, respectively. Functional network analysis showed that SKA3 regulated the mitotic cell cycle, mitosis, chromosome segregation and cell division via pathways. Conclusion In summary, our study suggested that SKA3 was highly expressed in LUAD and SKA3 might function as a prognostic biomarker in LUAD. Besides, SKA3 may be a candidate oncogene, which correlates with poor prognosis and immune infiltration in lung adenocarcinoma.

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“…Furthermore, they also found SKA3 expression exhibited a significantly negative correlation with the immune infiltration levels of B cells, macrophages, and CD4+ T cells. SKA3 showed a significant negative association with immune-type biomarkers specific to T cells and B cells in LUAD 69 . In vitro experiments demonstrated silencing SKA3 significantly inhibited cell proliferation and migration of LUAD and overexpression of SKA3 substantially accelerated cell proliferation, migration, and metastasis while suppressing apoptosis in NSCLC cells 66 , 70 , 71 .…”

“…Notably, LUAD exhibits a distressingly low 5-year survival rate of only 22.1% 65 . In LUAD patients, the expression of SKA3 was increased and associated with poor prognosis and lymph node metastasis 66 – 69 . In addition, the expression of SKA3 demonstrated a significant correlation with age, sex, pathologic stage, pathologic lymph node status, and pathologic metastasis status 67 .…”