Integrative Spatial Transcriptomics of Copper Driven Pathway Activity and Tumor Microenvironment Signaling in Colon Cancer
Ramini Paruchuri
Lay Summary:
This project was to study how colon cancer tumors use and process copper as different areas of the tumor rely on copper for different purposes. The findings from this study could eventually lead to more effective treatments/therapies that target these specific areas based on how copper related pathways influence them, offering a more strategic way to fight the disease.
Abstract:
Colon cancer, a leading cause for cancer deaths and third most common cancer, occurs from the abnormal growth of cells in the rectum. Past reports have shown increased copper (Cu) accumulation in colon tumor tissue and the presence of Cu has furthered the progression of colorectal cancer. Despite these findings, little is known about how copper is distributed within tumors and how it influences local gene expression and signaling in the tumor microenvironment (TME). The purpose of this study is to provide a spatial understanding of Cu biology in colon cancer, demonstrating how metabolic processes are organized into niches within the TME. To address this, spatial transcriptomics were applied to map the expression of a cuproptosis and copper metabolism related gene set in a human colon cancer sample that were identified in a pan-cancer genetic analysis. Genes were organized into copper transport, mitochondrial copper handling, and cuproptosis pathways followed by the calculation of corresponding pathway scores. Spatial autocorrelation analysis revealed non-random and clustered distribution of these pathways and dominant Cu regulators were identified using correlation analysis. SLC31A1 was the primary driver of copper transport activity (ρ=0.435, p<0.001) and FDX1 was the strongest correlate of the cuproptosis pathway (ρ=0.409, p<0.001). Future work for this study includes spatial mapping to identify Cu hotspot regions, an application of a deep learning model, such as a GNN, and understanding the influence of other trace metals.
Q&A:
Bios: Ramini Paruchuri
Program Track: Advanced Research
GitHub Username:
ramparu123 -Ramini Paruchuri
What was your favorite seminar? Why?
My favorite was either Zarif’s presentation or Rishy and Vismay’s. For me, Zarif’s presentation was a very good introduction into the internship and I learned a different perspective to modeling and its application. I also thought it was very interesting to see the entrepreneur side and how a start up can be implemented as long as you have a issue or topic to solve, even if it’s not that prevalent. Rishy and Vismay’s had a neuroscience aspect to it, which is my most preferred area of research and it was interesting to see a similar project to mine applied to a different condition. I also was able to learn a lot about my own project while listening to theirs, such as with the pathway analysis and a lot of the statistics. -Ramini Paruchuri
If you were to summarize your summer internship experience in one sentence, what would it be?
The internship exposed me to very interesting topics, even ones that I thought I might want to pursue in the future, but it also made me realize that I don’t know as much as I thought I did in this field and have to do a lot more application based learning to get a grasp on a lot of the concepts. -Ramini Paruchuri