Protein co-expression network-based profiles revealed from laser-microdissected cancerous cells of lung squamous-cell carcinomas

Abstract

No therapeutic targets have been identified for lung squamous cell cancer (SqCC) which is the second most prevalent lung cancer because its molecular profiles remain unclear. This study aimed to unveil disease-related protein networks by proteomic and bioinformatic assessment of laser-microdissected cancerous cells from seven SqCCs compared with eight representative lung adenocarcinomas. We identified three network modules significant to lung SqCC using weighted gene co-expression network analysis. One module was intrinsically annotated to keratinization and cell proliferation of SqCC, accompanied by hypoxia-induced aerobic glycolysis, in which key regulators were activated (HIF1A, ROCK2, EFNA1-5) and highly suppressed (KMT2D). The other two modules were significant for translational initiation, nonsense-mediated mRNA decay, inhibited cell death, and interestingly, eIF2 signaling, in which key regulators, MYC and MLXIPL, were highly activated. Another key regulator LARP1, the master regulator in cap-dependent translation, was highly suppressed although upregulations were observed for hub proteins including EIF3F and LARP1 targeted ribosomal proteins, among which PS25 is the key ribosomal protein in IRES-dependent translation. Our results suggest an underlying progression mechanism largely caused by switching to the cap-independent, IRES-dependent translation of mRNA subsets encoding oncogenic proteins. Our findings may help to develop therapeutic strategies to improve patient outcomes.

Data‐independent acquisition and quantification of extracellular matrix from human lung in chronic inflammation‐associated carcinomas

“…Two keratins, keratin, type I cytoskeletal 2 epidermal (KRT2) and keratin, type I cytoskeletal 9 (KRT9) were down‐regulated. The observed global upregulation of keratins in this study highlights the strong keratinization process observed during LSCC, as also previously reported in laser micro‐dissected tumor cells [ 80 ]. Interestingly, keratinization might be associated with smoking, a risk factor of lung CIAC, and keratinization correlates with poor clinical outcome in LSCC [ 81 ].…”

The Breast Cancer Protein Co-Expression Landscape

“…Protein co-expression networks are emerging as a valuable tool for the study of complex phenotypes, including pathological states such as tumors [ 37 , 38 , 39 ]. Gene co-expression networks have been quite successful, providing molecular insights into tumor biology, yet for obvious reasons, these are not able to account for post-transcriptional, translational and post-translational phenomena, which may constitute important players in cancer.…”

Protein interaction networks characterizing the A549 cells Klotho transfected are associated with activated pro-apoptotic Bim and suppressed Wnt/β-catenin signaling pathway

“…This study aimed to identify co-expression protein networks associated with A549/KL cells, compared with those of A549 cells, to understand how Klotho protein expression affects molecular networks associated with the malignant nature of lung carcinoma cells. Weighted gene co-expression network analysis (WGCNA), an unsupervised clustering method based on correlation network expression 14 , 15 was applied to quantitative proteome datasets. Then, Ingenuity Pathway Analysis was used to perform upstream analysis 16 of data-driven protein co-expression networks, and GeneMANIA 17 was used to identify interaction networks of proteins expressed characteristically in the A549 and A549/KL cells, respectively.…”