Establishment of a CALU, AURKA, and MCM2 gene panel for discrimination of metastasis from primary colon and lung cancers

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 webbased 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 normalcarcinoma 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.

Calumenin contributes to epithelial-mesenchymal transition and predicts poor survival in glioma

“…Under normal physiological conditions, CALU primarily participates in regulating Ca 2+ -dependent protein folding, sorting and maturation in the ER [ 31 ], Ca 2+ homeostasis [ 32 , 33 ], and muscle contraction/relaxation [ 34 ]. However, in tumor microenvironment, CALU was reported to play a critical role in promoting a series of malignant phenotypes including cancer cell survival [ 21 ], filopodia formation and cell migration [ 20 ], invasiveness [ 12 ], metastasis [ 15 , 35 ], cancer development [ 10 ], and resistance to chemotherapy [ 13 ]. So far, very little is known about the biological function of CALU in glioma.…”

“…Calumenin (CALU) has been widely reported in a range of malignancies including head and neck cancer [ 8 ], endometrial cancer [ 9 ], colon [ 10 ] and colorectal cancer [ 11 ], lung cancer [ 10 , 12 ], melanoma [ 13 ], hepatocellular and pancreatic carcinoma [ 14 ], and breast cancer [ 15 ]. CALU, a calcium-binding protein localized in the endoplasmic reticulum (ER), is mainly involved in such ER functions as protein folding and sorting.…”

The Epithelial to Mesenchymal Transition Related Gene Calumenin Is an Adverse Prognostic Factor of Bladder Cancer Correlated With Tumor Microenvironment Remodeling, Gene Mutation, and Ferroptosis

“…Kunita A et al demonstrated that CALU was secreted by cancerassociated fibroblasts (CAFs) and increased lung cancer cell proliferation (16). A recent manuscript by Nasri Nasrabadi P et al also indicated the metastasis promoting role of CALU in colon and lung cancers (17). From the above evidence, we could see the cancer-promoting and CAFs associated roles of CALU.…”

“…A recent manuscript by Nasri Nasrabadi P et al. also indicated the metastasis promoting role of CALU in colon and lung cancers ( 17 ). From the above evidence, we could see the cancer-promoting and CAFs associated roles of CALU.…”

Gene signatures and prognostic analyses of the Tob/BTG pituitary tumor-transforming gene (PTTG) family in clinical breast cancer patients

“…Meanwhile, analysis of a published high-throughput database indicated that PTTGs were highly expressed in metastatic breast cancer 33 , 34 . Through a Cytoscape analysis, we also found that PTTG family members had high correlations with metastasis markers such as NDC80 35 , AURKA 36 , AURKB 37 , and KIF2C 38 (Figure 2 G).…”