WDR62 overexpression is associated with a poor prognosis in patients with lung adenocarcinoma

Abstract

Human WDR62, which is localized in the cytoplasm including the centrosome, is known to be responsible for primary microcephaly; however, the role of WDR62 abnormality in cancers remains largely unknown. In this study, we aimed to reveal the pathological role of WDR62 abnormality in lung adenocarcinoma (LAC). We first examined the WDR62 mRNA expression level of LAC (n = 64) using a QRT-PCR analysis and found that WDR62 mRNA transcripts were significantly overexpressed in LAC (P = 0.0432, Wilcoxon matched pairs test). An immunohistochemical analysis for LAC (n = 237) showed that WDR62 proteins were also significantly overexpressed in LAC (P < 0.0001, Mann-Whitney U test). A Kaplan-Meier analysis demonstrated that patients with LAC who exhibit WDR62 overexpression have a short overall survival (P = 0.0378, log-rank test), and a multivariate analysis revealed that WDR62 overexpression was an independent predictor of a poor survival outcome among LAC patients (hazard ratio, 2.032; 95% confidence interval, 1.071-3.777; P = 0.0305). Next, we examined the functional effect of WDR62 overexpression on the lung cancer cell line H1299. WDR62-overexpressing lung cancer cells exhibited an increase in cell growth. Moreover, the concurrent overexpression of WDR62 and TPX2, a WDR62-interacting protein that is also overexpressed in LAC, induced centrosome amplification in the lung cells. Finally, we disclosed that the concurrent overexpression of WDR62 and TPX2 is common in diverse human cancers, using data from the Cancer Genome Atlas. These results suggested that WDR62 overexpression is associated with a poor prognosis in patients with LAC and leads to an increase in the malignant potential of lung cells.

Gene set enrichment analysis and meta‑analysis identified 12 key genes regulating and controlling the prognosis of lung adenocarcinoma

“…Although lung adenocarcinoma is the most common primary lung neoplasm (16), its causes and underlying molecular mechanisms have not been fully elucidated (17). Previous studies primarily focused on a single factor that may lead to the development of lung adenocarcinoma (18,19); however, a single theory cannot provide a detailed explanation for all the different cases of lung adenocarcinoma.…”

STIL balancing primary microcephaly and cancer

“…WD repeat-containing protein62 (WDR62), whose deficiency is associated with MCPH2 68 – 70 , is required for maintaining spindle and centrosome integrity. Its overexpression, coincident with centrosome amplification, is also seen in lung adenocarcinomas and ovarian cancers 71 , 72 . WDR62 interacts physically during the cell cycle with the abnormal spindle-like microcephaly-associated protein (ASPM), whose deficiency causes the most frequent primary microcephaly (MCPH5) 73 .…”

The Yin and Yang of Autosomal Recessive Primary Microcephaly Genes: Insights from Neurogenesis and Carcinogenesis

“…The knockdown or inhibited expression of these genes may be a potential therapeutic method for cancer treatment [31][32][33]. In addition, the overexpression of MCPH2, MCPH5, MCPH7, MCPH14, MCPH20, MCPH21, MCPH23, and MCPH24 is associated with aggressiveness and poor outcome in patients with cancer [28,[34][35][36][37][38][39]. However, MCPH1 and MCPH15 are downregulated in tumor tissues or cancer cell lines and are considered as novel tumor suppressor genes [40,41].…”

“…Mitotic spindle orientation [43] Cell cycle (gastric cancer, GC) [44] Regulating intermediate neural and glial progenitors [45] Centrosome amplification (ovarian cancer, OC) [46] Cell cycle, centriole biogenesis, and mitotic spindle orientation [17] Cell growth (lung adenocarcinoma) [34] Regulating neural stem cell division [47,48]…”