Multi-omics characterization of Microtubule-actin cross linking factor 1 (MACF1) using the ISB-Cancer Genomics Cloud

Abstract

Establishment of cell polarity across cell types and organisms involves distinct mechanisms that follow a common pattern: first a polarity cue arises, followed by asymmetric organization executed by polarity proteins. Loss of cell polarity has a key role in cancer development. The MACF1 gene, Microtubule actin cross-linking factor 1, or MACF1, a cytoskeletal protein is involved in oocyte development, cell proliferation, and cell migration. In addition to these roles, MACF1 is linked to metastatic invasion leading to tumor progression in numerous human cancers including gynecological cancers of endometrial and ovarian cancer. Given the functional importance of cell polarity, here we provide computational evidence of MACF1 in gynecological cancers. The comparison of multi-omic data for patient tumor and normal cells facilitates the understanding of the molecular mechanisms that contribute to tumor cell proliferation, abnormal cell adhesion and cell migration. Leveraging the rich datasets hosted by the NCI-funded ISB-Cancer Genomics Cloud, we performed a cloud-based patient cohort analysis across diverse multi-omics datasets. We quantified differential gene expression profiles from patients in the cohort as well as identified somatic mutation differences. The most common genomic alteration for MACF1 was the in-frame mutation. Genomic alterations and mutations were aligned to functional domains of the MACF1 protein to determine both frequency and spatial distribution. Gene-gene expression correlation analyses identified statistically significant correlations between MACF1 and other well-known cancer driver genes. Together, using a data driven cloud-computing approach we gain novel insights into the role of MACF1 regulation of cell polarity in the progression of cancer.