Mutational analysis revealed 97 key cancer metastasis genes from extracellular vesicles associated with patient survival

Abstract

Extracellular vesicles (EVs) are small membrane vesicles secreted into the extracellular environment to play important roles in intercellular communications. Although there are some examples linking EVs to metastasis, there is a knowledge gaps about the common and unique roles for EVs in different cancer types. These systematic examination across different cancer types might provide the cancer specific metastatic mechanism. To this aim, we performed an integrative analysis on the literatures, thousands of cancer individuals, and reliable ligand-receptor information to present the first global analysis between EVs and metastasis. We identified 97 reliable genes present in EVs that contribute to metastasis with literature evidences. By exploring functional, network, and mutational features of these 97 genes, we found proteoglycans and microRNAs in cancer development might be the key links between EV and cancer metastasis. Most importantly, these 97 genes are significantly associated with cancer patient survival from a combination of 4975 cancer patients from various cancer types. The additional ligand-receptor network were reconstructed to reveal the cellular communication mechanisms for these key EV genes in cancer metastasis. Since the circulating EVs in body fluids could be a candidate for non-invasive liquid biopsy, our results provide a reliable resource of EV-related miRNAs and proteins important for cancer metastasis monitoring.