Abstract
Metastasis is known as a key step in cancer recurrence and could be stimulated by multiple factors. Calumenin (CALU) is one of these factors which has a direct impact on cancer metastasis and yet, its underlined mechanisms have not been completely elucidated. The current study was aimed to identify CALU co-expressed genes, their signaling pathways, and expression status within the human cancers. To this point, CALU associated genes were visualized using the Cytoscape plugin BisoGenet and annotated with the Enrichr web-based application. The list of CALU related diseases was retrieved using the DisGenNet, and cancer datasets were downloaded from The Cancer Genome Atlas (TCGA) and analyzed with the Cufflink software. ROC curve analysis was used to estimate the diagnostic accuracy of DEGs in each cancer, and the Kaplan–Meier survival analysis was performed to plot the overall survival of patients. The protein level of the signature biomarkers was measured in 40 biopsy specimens and matched adjacent normal tissues collected from CRC and lung cancer patients. Analysis of CALU co-expressed genes network in TCGA datasets indicated that the network is markedly altered in human colon (COAD) and lung (LUAD) cancers. Diagnostic accuracy estimation of differentially expressed genes showed that a gene panel consisted of CALU, AURKA, and MCM2 was able to successfully distinguish cancer tumors from healthy samples. Cancer cases with abnormal expression of the signature genes had a significantly lower survival rate than other patients. Additionally, comparison of CALU, AURKA, and MCM2 proteins between healthy samples, early and advanced tumors showed that the level of these proteins was increased through normal–carcinoma transition in both types of cancers. These data indicate that the interactions between CALU, AURKA, and MCM2 has a pivotal role in cancer development, and thereby needs to be explored in the future.
Highlights
Calumenin (CALU) is a known member of the CREC protein family
The molecular interaction between CALU and other genes was analyzed by the Cytoscape plugin BisoGenet, and the final network consisted of 127 nodes and 739 interactions
Tumor metastasis is defined as cancer cell migration from the primary site to distant locations and plays a critical role in cancer recurrence and mortality [27, 28]
Summary
Calumenin (CALU) is a known member of the CREC protein family. It is encoded from the 7q32 region of the human genome and translated into a 315 amino acid protein containing a common CREC signal sequence, a putative N-glycosylation region, 6 ~ 7 EF-hand motifs, and a carboxyl-terminal with an inefficient retention HDEF signal sequence [1]. Unlike the other CREC family members, CALU proteins can only be transported via cellular secretory mechanisms, and most of the CALU isoforms (CALU 1–14) are detected in the endoplasmic reticulum (ER), Golgi apparatus and extracellular medium [3,4,5]. CALU can modulate the cellular stress through regulation of GRP78 and phosphorylated PERK as ER-stress factors, C/EBP homologous protein (CHOP), and p-JNK proapoptotic proteins, and antiapoptotic Bcl-2 [3]. Elevation of CALU extracellular isoforms ameliorates SEPT1 expression and increases cell cycle modulation [8]
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