Urine Proteins In Cancer and NGS

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John Catanzaro

Co-Founder / CIO at NEO7 Cancer Hallmark Analytics and Immunocentrics

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2019 John A. Catanzaro

Introduction

When profiling a certain cancer, it is vitally important to include all avenues of data available. Urine proteomics in combination with NGS (Next Generation Sequencing) is a very powerful parallel in understanding profiling of the tumor microenvironment and excretion behavior of a particular evolution known in cancer. However, as a solo analysis it is incomplete.

NGS profiles genes that are associated with tumor development, proliferation and resistance. Urine proteomics distinguishes excretion products that may be associated with certain immune proteins, metabolic remnant proteins and other important biomarkers that may not be discovered by NGS as a solo analysis. Moreover, the urine proteins that are uniquely expressed in a particular cancer can then become the product base for a precision treatment design for a patient.

Cancer Related Urine Proteins

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There can be well over 1000 different identified proteins excreted in the urine and the key is to isolate the high confidence and unique proteins to the cancer expression. Through proteomic analysis, isolation and comparison unique cancer biomarkers are captured for downstream applications of diagnosis and therapeutic applications. This figure is an example of the unique proteins isolated in head and neck cancer. The values of the significantly different levels of proteins found in urinary proteome of head and neck squamous cell carcinoma (HNSCC) patients (full bars) and thyroid cancer patients (dashed bars) in comparison to the healthy subjects. Red/positive and blue/negative bars correspond respectively to up- and down-secreted proteins in tumor patients compared to healthy subjects. Many different cancer types are profiled in this fashion with accuracy and actionable results. https://www.mdpi.com/1420-3049/24/4/794/htm#app1-molecules-24-00794

Sample Patient With Melanoma Urine Proteomics

When I was in clinical practice from 1996–2014, I have performed many urine proteomic studies on my patients with advanced stage cancer with the sole purpose of developing a targeted personalized treatment application. I am giving one of many examples of a patient with advanced stage 4 melanoma with metastasis to brain, lungs, intestinal tract and bones.

Urine proteomic analysis of a sample patient with stage 4 melanoma demonstrated 1154 low confidence proteins isolated from urine. 115 of these proteins were considered high unique confidence proteins. Bioinformatic and biocomputation demonstrated that 10 unique proteins are demonstrated in the literature with overexpression in advanced melanoma. 19 unique proteins have a connection with overexpression in cancer.

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Most interestingly, this patient’s urine proteins overexpressed unique proteins related to melanoma and progression of the disease. 20 unique proteins were selected and matched to the patients HLA compatibility. The patient-matched HLA immunogenic peptide sequences of each of the 20 melanoma related proteins were synthesized and arranged in a pooled neoantigen vaccine and given to the patient. The patient tolerated treatment well and his cancer regressed within 9 months and he is 8 years cancer free. I have included a screenshot of the final proteins selected and a sample of HLA sequences that were analyzed for the final neoantigen vaccine selection. This work was accomplished in 2011 before neoantigens became the fashionable nomenclature. NEO7 continues to be ahead of the curve in this biochip integration, mapping and delivery.

NEO7 BioChip Integration Platform

We have many other patient samples in a variety of end stage cancer types that demonstrate some astounding relationships and outcomes. We are sharing this to demonstrate how much more power there is now with our NEO7 BioChip robust platform integration. Our platform combines all omics data including NGS, Tumor RNAseq, urine proteomics along with AI / BI biocomputation and bioinformatics and distinctly maps and selects high affinity cancer biology and HLA allele compatibility of the patient. We have many patient prototypes in process to demonstrate the elite ability to precision profile, map, select and deliver the “best fit” therapeutic application specific to the patient.

In Summary

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NGS analysis alone is incomplete and failure to understand the value of HLA relationships is of extreme importance in profiling, mapping and selecting an individualized patient therapeutic application. Combined urine proteomics and BioChip integration for cancer -related biomarkers and prospective therapeutic applications are essential.

Chromosome 6 is the epicenter of cancer immunoediting and HLA affinity is a integral part of comprehending real time and predictive immunoediting features, actions and ability.

NEO7 is truly providing the elite integration in personalized precision-based immune defense against cancer and other complex diseases. The big picture of cancer evolution and adaptation requires an evolving anti-cancer defense action integration. HLA and chromosome 6 are central players for strategic intervention to counter cancer immune escape. Two key considerations in anti-cancer defenses are: Cancer Evolution and Chromosome 6

John A. Catanzaro is CEO of Neo7logix, a bioscience company that designs precision and personalized treatment designs. www.neo7logix.com

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