Aberrant expression of mRNA is widely considered a distinct characteristic of the development and progression of various cancers, especially lung cancer. To investigate the dysregulation of mRNA expression in NSCLC, our group integrated the results of five NSCLC transcriptome microarray datasets that are widely considered to have high credibility. Additionally, these five datasets were downloaded from different platforms, which allowed us to avoid the biases of the platforms. By integrating these five datasets, we largely ensured the credibility of our results. Our research suggests that PLEK2 and SCN7A may be used as potential biological markers for the early diagnosis of NSCLC.
Some of our DEGs were believed to be associated with lung adenocarcinoma in previous studies, such as TPX2 , IGF2BP3 , ANKRD22 , TMPRSS4 , SPP1 , MMP1 [20, 21], MMP12 , UBE2T , ECT2 [24, 25], SULF1 , HMGB3 , and CTHRC1 [28, 29]. Besides, we identified PLEK2 and SCN7A as potential biomarkers of NSCLC. PLEK2 was first cloned in 1999, and it is widely expressed in diverse adherent cell lines [30, 31]. It is thus tempting to consider that PLEK2 is related to cytoskeletal rearrangement and cell spreading, as well as the development of large lamellipodia . Moreover, lamellipodia are widely believed to participate in angiogenesis by endothelial cells and metastasis by melanoma cells [33–35]. Hamaguchi also reported that PLEK2 induced PI3-kinase-dependent F-actin reorganization and cell spreading . Consistent with this hypothesis, our study revealed that PLEK2 may result in poor prognosis by enhancing the efficiency of tumor growth and the metastasis of NSCLC cells. SCN7A encodes a voltage-dependent sodium channel of the excitable membrane, and it is reported to be downregulated in colorectal carcinoma at the mRNA level . However, the antitumor activity of SCN7A is unknown. Therefore, more elaborative research is needed.
Similarly, Liu reported that low eIF3a expression is a negative factor in the development of colonic carcinoma [38, 39]. In addition, KEGG pathway analysis indicated that the PPAR signaling pathway, cell adhesion molecules, and ECM-receptor interaction were the most significantly enriched pathways. Our results indicated some of these genes, which were found to play critical roles in the promotion of EMT and the invasion and migration of cells in previous studies [40, 41], were associated with the PPAR signaling pathway. Furthermore, the PPAR signaling pathway is related to cell adhesion and apoptosis , which is consistent with our results of GO analysis. PPAR, the isoforms of which include PPARα, PPARβ, and PPARγ, belongs to the nuclear hormone receptor superfamily. PPARγ controls tumor growth, cell proliferation, and cell invasiveness by inhibiting various signaling pathways such as the JAK/STAT, transforming growth factor (TGF), WNT/β-catenin, and PI3K/ Akt pathways . TGF is related to the occurrence and development of various cancer-related diseases [44, 45]. Furthermore, previous studies indicated that TGF promoted the malignancy, differentiation, and metastasis of tumors, such as NSCLC, pancreatic cancer, and colon cancer [46–49], by inducing EMT. Evidences have shown that the PPAR receptor was frequently overexpressed in lung cancer [50, 51]. Recent studies [51, 52] indicated that TGF induces EMT through the PPAR pathway, leading to the differentiation, metastasis, and malignant transformation of lung cancer cells. In addition, PPARγ induces MUC1-C ubiquitination and degradation, which are associated with various cancers such as colon, breast, ovarian, lung, and pancreatic cancers .Collectively, these observations indicate that PPAR signaling pathway may participate in NSCLC progression.