Cancer Players Revealed in Proteomic Analysis

Baylor College of Medicine researchers conducted an extensive computational analysis of the similarities and differences in the proteome of over 500 cancers from five different tissue sites. Published in the journal Nature Communications, the work led to the classification of the cancers into 10 subtypes.

The proteomic analysis confirmed the involvement of previously known molecular players in cancer, and it also revealed others that have not appeared in previous analyses. The findings present novel molecular pathways that can be investigated with regards to their potential involvement in cancer.

“Cancer is currently understood not as a single disease but as a collection of diseases,” says senior author Chad Creighton. “Cancer can develop through alterations in different molecular pathways, and in this study, we applied data from molecular profiling technologies to sort out protein alterations that could be linked to cancer.”

Analysis of the protein data led to the classification of the cancers into 10 subtypes, each with a distinct set of protein alterations. The subtypes included multiple organ tissue sites sharing common altered molecular pathways. Knowing the pathways opens up potential therapeutic opportunities.

“We found that many of the subtypes that we had found based on mRNA observations that we made before held up when we looked at the protein level,” Creighton says. “Interestingly, four of these 10 subtypes actually do not involve the cancer cells themselves. They represent differences in the tumor microenvironment, the cells and tissues that surround the tumor, and these subtypes are very distinct from each other.”

Two of the four subtypes involved immune components that were associated with the tumor microenvironment. The first immune subtype was characterized by the presence of immune T cells. The second immune subtype, on the other hand, highlighted the complement activation pathway, which is an important component of tumor-promoting inflammation that is thought to play a role in cancer initiation and progression. Previous studies appear to have missed the complement pathway as being associated with cancer subtypes.

“Some of the pathways we found associated with these three subtypes may not be commonly associated with human cancers, but links to them have been found,” Creighton says. “One subtype involved the Golgi apparatus of the cell. Reports have linked the Golgi to malignant transformation, for instance. Another subtype, which was specific to renal carcinoma, was associated with hemoglobin increases. Finally, the third subtype involved the endoplasmic reticulum, an intracellular component.”