The age of fast, accurate, and noninvasive cancer screening is rapidly becoming reality. The power of next-generation sequencing has allowed molecular diagnostic techniques to sample small amounts of blood for the genetic hallmarks of tumorigenesis. These liquid biopsy procedures, as they have been dubbed, typically search for circulating tumor DNA (ctDNA) that has made its way into the systemic circulation from tumor cells that have died or enrich for circulating tumor cells (CTCs) that have broken off from the primary cancer site.
Now, a team of researchers lead by scientists at Massachusetts General Hospital (MGH), have developed a new diagnostic test that analyzes the tumor RNA picked up in circulating platelets. The investigators believe this new method could become even more useful than other molecular technologies for diagnosing cancer since it can also determine the primary location of the tumor and provide insight to potential therapeutic approaches.
"By combining next-generation-sequencing gene expression profiles of platelet RNA with computational algorithms we developed, we were able to detect the presence of cancer with 96 percent accuracy," explains co-senior author Bakhos Tannous, Ph.D., associate professor Harvard Medical School and associate neuroscientist at MGH. "Platelet RNA signatures also provide valuable information on the type of tumor present in the body and can guide the selection of the most optimal treatment for individual patients.
The findings from this study were published recently in Cancer Cell through an article entitled “RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics.”
In the current study the research team describes finding that the RNA profiles of tumor-educated platelets (TEPs)—those that have taken up molecules shed by tumors—can distinguish among blood samples of healthy individuals and those of patients with six types of cancer, determine the location of the primary tumor, and identify tumors carrying mutations that can guide therapeutic decision-making.
Over the past several years, the scientific literature has shown that in addition to their role in promoting blood clotting, platelets take up protein and RNA molecules from tumors, possibly playing a role in tumor growth and metastasis. Dr. Tannous and his colleagues set out to determine whether tumor RNA carried in platelets could be used to diagnose and classify common types of cancer.
The investigators isolated platelets from blood samples taken from 55 healthy donors, 39 individual with early-stage cancer and 189 patients with advanced, metastatic cancer. Among those patients with cancer, they were diagnosed with non-small-cell lung cancer, colorectal cancer, glioblastoma, pancreatic cancer, hepatobiliary cancer, or breast cancer.
The comparison of RNA profiles from the healthy donors to those of the cancer patients identified increased levels of approximately 1,500 RNA molecules—many involved in cancer-associated processes—and a reduction of almost 800 in samples from cancer patients. Using their novel algorithm, the MGH group was able to examine close to 1,000 RNAs from almost 300 individuals with 96% accuracy for the presence of cancer.
Additionally, the platelet mRNA profiles were able to identify the particular type of cancer within each patient participant, including distinguishing among three types of gastrointestinal adenocarcinoma: colorectal cancer, pancreatic cancer, and hepatobiliary cancer. Platelets from patients with tumors driven by mutations in KRAS or EGFR proteins—biomarkers that can guide the use of drugs targeting those mutations—proved to have unique RNA profiles as well.
The researchers were excited by their findings and emphasize the uniqueness of their approach as currently utilized liquid biopsy approaches have been unable to diagnose cancer while simultaneously pinpointing the location of the primary tumor.
"We observed that the mRNA profiles of tumor-educated platelets have the sensitivity and specificity to detect cancer, even in early, non-metastasized tumors," noted Dr. Tannous. "We are further assessing the potential of TEP-based screening for therapeutic decision making and also investigating how non-cancerous diseases may further influence the RNA repertoire of TEPs."