MYLK and MYL9 expression in non-small cell lung cancer identified by bioinformatics analysis of public expression data

Abstract

Gene expression microarrays are widely used to investigate molecular targets in cancers, including lung cancer. In this study, we analyzed online non-small cell lung cancer (NSCLC) microarray databases, to screen the key genes and pathways related to NSCLC by bioinformatics analyses. And then, the expression levels of two selected genes in the down-regulated co-pathways, myosin light chain kinase (MYLK) and myosin regulatory light chain 9 (MYL9), were determined in tumor, paired paraneoplastic, and normal lung tissues. First, gene set enrichment analysis and meta-analysis were conducted to identify key genes and pathways that contribute to NSCLC carcinogenesis. Second, using the total RNA and protein extracted from lung cancer tissues (n = 240), adjacent non-cancer tissues (n = 240), and normal lung tissues (n = 300), we examined the MYLK and MYL9 expression levels by quantitative real-time PCR and Western blot. Finally, we explored the correlations between mRNA and protein expressions of these two genes and the clinicopathological parameters of NSCLC. Fifteen up-regulated and nine down-regulated co-pathways were observed. A number of differentially expressed genes (CALM1, THBS1, CSF3, BMP2, IL6ST, MYLK, ROCK2, IL3RA, MYL9, PPP2CA, CSF2RB, CNAQ, GRIA2, IL10RA, IL10RB, IL11RA, LIFR, PLCB4, and RAC3) were identified (P < 0.01) in the down-regulated co-pathways. The expression levels of MYLK and MYL9, which act downstream of the vascular smooth muscle contraction signal pathway and focal adhesion pathway, were significantly lower in cancer tissue than those in the paraneoplastic and normal tissues (P < 0.05). Moreover, the expression levels of these two genes in stages III and IV NSCLC were significantly increased, when compared to stages I and II, and expressions levels in NSCLC with lymphatic metastasis were higher than that without lymphatic metastasis (P < 0.05). Additionally, significant lower expression levels of the two genes were found in smokers than in nonsmokers (P < 0.05). In contrast, gender, differentiated degrees, and pathohistological type appeared to have no impact on these gene expressions (P > 0.05). These findings suggested that low MYLK and MYL9 expressions might be associated with the development of NSCLC. These genes may be also relevant to NSCLC metastasis. Future investigations with large sample sizes needed to verify these findings.

Expression and prognostic significance of MYL9 in esophageal squamous cell carcinoma

“…High MYL9 expression is associated with lymphatic metastasis in non–small cell lung cancer[19]. However, we observed no correlation between MYL9 expression and regional lymph node metastasis.…”

“…Low MYL9 expression correlated with poor survival in colon and prostate cancer, suggesting that MYL9 is a favorable prognostic marker [18, 20]. On the other hand, high MYL9 expression was significantly associated with late tumor-node-metastasis (TNM) stage and lymphatic metastasis in non–small cell lung cancer[19]. Nevertheless, studies on the association between MYL9 expression and cancer are rare, and there has been no published report on the characteristics of MYL9 expression and its clinical significance in ESCC.…”

WITHDRAWN: Molecular pathological signatures of gastric cancer in Koreans revealed by label-free proteomics

“…However, Myosin Heavy Chain 9, non-muscle (MYH9) was up-regulated. Among these proteins, MYL9[18], TPM1[19] and MYH9[20] are known to be involved in tumorigenesis in various cancers. Other down-regulated components included intermediate filament components such as Vimentin and Desmin (Fig.…”

Data-Driven Discovery of Extravasation Pathway in Circulating Tumor Cells

“…SPARC (also observed as top molecule in unsupervised clustering) is a well-known marker associated with invasion and an important mediator of bone metastasis8990. Interestingly, MYLK and CD9 have been implicated in lymph node metastasis in different cancers9192, whereas ABCC3 overexpression is reportedly involved in glycolysis, drug resistance and overall poor prognosis in bladder cancer [not in our dataset]8993. However, some markers may play a tumor-specific role, as the loss of FHL1 has been linked with increased metastasis in esophageal and gastric cancers9394 [these cancers are not represented in our dataset].…”