Molecular bases of morphologically diffused tumors across multiple cancer types

Abstract

Gastric cancer has two distinct subtypes: the diffuse (DGC) and the intestinal (IGC) subtypes. Morphologically, the former each consists of numerous scattered tiny tumors while the latter each has one or a few solid biomasses. The former tends to be more aggressive and takes place in younger patients than the latter. While these have long been documented, little is known about the underlying causes. Our hypothesis is that the level of sialic acid (SA) accumulation on the cancer cell surfaces is a key reason for the observed differences. Our transcriptomic data-based analyses provide evidence that (i) DGCs tend to deploy more SAs on cancer cell surfaces than IGCs; (ii) this gives rise to considerably stronger cell–cell electrostatic repulsion in DGCs due to the negative charge that each SA carries; and (iii) such repulsion drives stronger cell protrusion and metastasis. Similar observations as well as our transcriptomic data-based predictions hold for multiple other cancer types, namely breast, lung, prostate plus liver and thyroid cancers, each known to have diffuse-like vs. non-diffused subtypes as well as more aggressive behaviors like DGCs vs. IGCs. Hence, we speculate that the discovery presented here applies not only to gastric cancer but multiple and even potentially all cancer types having diffuse-like and non-diffused subtypes.