Best of all, the researchers say the test could provide an inexpensive means of early diagnosis. This assay could also be used to monitor how well patients respond to cancer therapy, according to a news release.
The protein had previously been identified as a promising biomarker and is readily detectable in tumor tissue, they wrote. However, it is found in extremely low concentrations in blood plasma and is “well below detection limits of conventional clinical laboratory methods,” they noted.
To overcome that obstacle, they employed an ultra-sensitive immunoassay known as a Simoa (Single-Molecule Array), an immunoassay platform for measuring fluid biomarkers.
“We were shocked by how well this test worked in detecting the biomarker’s expression across cancer types,” said lead study author gastroenterologist Martin Taylor, MD, PhD, Instructor in Pathology, Massachusetts General Hospital and Harvard Medical School, in the press release. “It’s created more questions for us to explore and sparked interest among collaborators across many institutions.”
“We’ve known since the 1980s that transposable elements were active in some cancers, and nearly 10 years ago we reported that ORF1p was a pervasive cancer biomarker, but, until now, we haven’t had the ability to detect it in blood tests,” said pathologist and study co-author Kathleen Burns, MD, PhD (above), Chair of the Department of Pathology at Dana-Farber Cancer Institute and a Professor of Pathology at Harvard Medical School, in a press release. “Having a technology capable of detecting ORF1p in blood opens so many possibilities for clinical applications.” Clinical laboratories may soon have a new blood test to detect multiple types of cancer. (Photo copyright: Dana-Farber Cancer Institute.)
Simoa’s Advantages
In their press release, the researchers described ORF1p as “a hallmark of many cancers, particularly p53-deficient epithelial cancers,” a category that includes lung, breast, prostate, uterine, pancreatic, and head and neck cancers in addition to the cancers noted above.
“Pervasive expression of ORF1p in carcinomas, and the lack of expression in normal tissues, makes ORF1p unlike other protein biomarkers which have normal expression levels,” Taylor said in the press release. “This unique biology makes it highly specific.”
Simoa was developed at the laboratory of study co-author David R. Walt, PhD, the Hansjörg Wyss Professor of Bioinspired Engineering at Harvard Medical School, and Professor of Pathology at Harvard Medical School and Brigham and Women’s Hospital.
The Simoa technology “enables 100- to 1,000-fold improvements in sensitivity over conventional enzyme-linked immunosorbent assay (ELISA) techniques, thus opening the window to measuring proteins at concentrations that have never been detected before in various biological fluids such as plasma or saliva,” according to the Walt Lab website.
Simoa assays take less than two hours to run and require less than $3 in consumables. They are “simple to perform, scalable, and have clinical-grade coefficients of variation,” the researchers wrote.
Study Results
Using the first generation of the ORF1p Simoa assay, the researchers tested blood samples of patients with a variety of cancers along with 406 individuals, regarded as healthy, who served as controls. The test proved to be most effective among patients with colorectal and ovarian cancer, finding detectable levels of ORF1p in 58% of former and 71% of the latter. Detectable levels were found in patients with advanced-stage as well as early-stage disease, the researchers wrote in Cancer Discovery.
Among the 406 healthy controls, the test found detectable levels of ORF1p in only five. However, the control with the highest detectable levels, regarded as healthy when donating blood, “was six months later found to have prostate cancer and 19 months later found to have lymphoma,” the researchers wrote.
They later reengineered the Simoa assay to increase its sensitivity, resulting in improved detection of the protein in blood samples from patients with colorectal, gastroesophageal, ovarian, uterine, and breast cancers.
The researchers also employed the test on samples from 19 patients with gastroesophageal cancer to gauge its utility for monitoring therapeutic response. Although this was a small sample, they found that among 13 patients who had responded to therapy, “circulating ORF1p dropped to undetectable levels at follow-up sampling.”
“More Work to Be Done”
The Simoa assay has limitations, the researchers acknowledged. It doesn’t identify the location of cancers, and it “isn’t successful in identifying all cancers and their subtypes,” the press release stated, adding that the test will likely be used in conjunction with other early-detection approaches. The researchers also said they want to gauge the test’s accuracy in larger cohorts.
“The test is very specific, but it doesn’t tell us enough information to be used in a vacuum,” Walt said in the news release. “It’s exciting to see the early success of this ultrasensitive assessment tool, but there is more work to be done.”
More studies will be needed to valid these findings. That this promising new multi-cancer immunoassay is based on a clinical laboratory blood sample means its less invasive and less painful for patients. It’s a good example of an assay that takes a proteomic approach looking for protein cancer biomarkers rather than the genetic approach looking for molecular DNA/RNA biomarkers of cancer.
Scientists believe useful new clinical laboratory assays could be developed by better understanding the huge number of ‘poorly researched’ genes and the proteins they build
Researchers have added a new “-ome” to the long list of -omes. The new -ome is the “unknome.” This is significant for clinical laboratory managers because it is part of an investigative effort to better understand the substantial number of genes, and the proteins they build, that have been understudied and of which little is known about their full function.
The Unknome Database includes “thousands of understudied proteins encoded by genes in the human genome, whose existence is known but whose functions are mostly not,” according to a news release.
The database, which is available to the public and which can be customized by the user, “ranks proteins based on how little is known about them,” the PLOS Biology paper notes.
It should be of interest to pathologists and clinical laboratory scientists. The fruit of this research may identify additional biomarkers useful in diagnosis and for guiding decisions on how to treat patients.
“These uncharacterized genes have not deserved their neglect,” said Sean Munro, PhD (above), MRC Laboratory of Molecular Biology in Cambridge, England, in a press release. “Our database provides a powerful, versatile and efficient platform to identify and select important genes of unknown function for analysis, thereby accelerating the closure of the gap in biological knowledge that the unknome represents.” Clinical laboratory scientists may find the Unknome Database intriguing and useful. (Photo copyright: Royal Society.)
Risk of Ignoring Understudied Proteins
Proteomics (the study of proteins) is a rapidly advancing area of clinical laboratory testing. As genetic scientists learn more about proteins and their functions, diagnostics companies use that information to develop new assays. But did you know that researchers tend to focus on only a small fraction of the total number of protein-coding DNA sequences contained in the human genome?
The study of proteomics is primarily interested in the part of the genome that “contains instructions for building proteins … [which] are essential for development, growth, and reproduction across the entire body,” according to Scientific American. These are all protein-coding genes.
Proteomics estimates that there are more than two million proteins in the human body, which are coded for 20,000 to 25,000 genes, according to All the Science.
To build their database, the MRC researchers ranked the “unknome” proteins by how little is known about their functions in cellular processes. When they tested the database, they found some of these less-researched proteins important to biological functions such as development and stress resistance.
“The role of thousands of human proteins remains unclear and yet research tends to focus on those that are already well understood,” said Sean Munro, PhD, MRC Laboratory of Molecular Biology in Cambridge, England, in the news release. “To help address this we created an Unknome database that ranks proteins based on how little is known about them, and then performed functional screens on a selection of these mystery proteins to demonstrate how ignorance can drive biological discovery.”
In the paper, they acknowledged the human genome encodes about 20,000 proteins, and that the application of transcriptomics and proteomics has “confirmed that most of these new proteins are expressed, and the function of many of them has been identified.
“However,” the authors added, “despite over 20 years of extensive effort, there are also many others that still have no known function.”
They also recognized limited resources for research and that a preference for “relative safety” and “well-established fields” are likely holding back discoveries.
The researchers note “significant” risks to continually ignoring unexplored proteins, which may have roles in cell processes, serve as targets for therapies, and be associated with diseases as well as being “eminently druggable,” Genetic Engineering News reported.
Setting up the Unknome Database
To develop the Unknome Database, the researchers first turned to what has already come to fruition. They gave each protein in the human genome a “knownness” score based on review of existing information about “function, conservation across species, subcellular localization, and other factors,” Interesting Engineering reported.
It turns out, 3,000 groups of proteins (805 with a human protein) scored zero, “showing there’s still much to learn within the human genome,” Science News stated, adding that the Unknome Database catalogues more than 13,000 protein groups and nearly two million proteins.
The researchers then tested the database by using it to determine what could be learned about 260 “mystery” genes in humans that are also present in Drosophila (small fruit flies).
“We used the Unknome Database to select 260 genes that appeared both highly conserved and particularly poorly understood, and then applied functional assays in whole animals that would be impractical at genome-wide scale,” the researchers wrote in PLOS Biology.
“We initially selected all genes that had a knownness score of ≤1.0 and are conserved in both humans and flies, as well as being present in at least 80% of available metazoan genome sequences. … After testing for viability, the nonessential genes were then screened with a panel of quantitative assays designed to reveal potential roles in a wide range of biological functions,” they added.
“Our screen in whole organisms reveals that, despite several decades of extensive genetic screens in Drosophila, there are many genes with essential roles that have eluded characterization,” the researchers conclude.
Clinical Laboratory Testing Using the Unknome Database
Future use of the Unknome Database may involve CRISPR technology to explore functions of unknown genes, according to the PLOS Biology paper.
Munro told Science News the research team may work with other research efforts aimed at understanding “mysterious proteins,” such as the Understudied Proteins Initiative.
The Unknome Database’s ability to be customized by others means researchers can create their own “knownness” scores as it applies to their studies. Thus, the database could be a resource in studies of treatments or medications to fight diseases, Chemistry World noted.
According to a statement prepared for Healthcare Dive by SomaLogic, a Boulder, Colorado-based protein biomarker company, diagnostic tests that measure proteins can be applied to diseases and conditions such as:
“The 27-protein model has potential as a ‘universal’ surrogate end point for cardiovascular risk,” the researchers wrote in Science Translational Medicine.
Proteomics definitely has its place in clinical laboratory testing. The development of MRC-LMB’s Unknome Database will help researchers’ increase their knowledge about the functions of more proteins which should in turn lead to new diagnostic assays for labs.
Clinical laboratories and pathologists should expect to receive increase referrals from oncologists with younger patients
More people are getting serious cases of cancer at younger and younger ages. So much so that some anatomic pathologists and epidemiologists are using the term “Turbo Cancers” to describe “the recent emergence of aggressive cancers that grow very quickly,” Vigilant News reported.
Cancer continues to be the second leading cause of death in the United States and current trends of the disease appearing in younger populations are causing alarm among medical professionals and scientists.
“Because these cancers have been occurring in people who are too young to get them, basically, compared to the normal way it works, they’ve been designated as turbo cancers,” Harvey Risch, MD, PhD, Professor Emeritus of Epidemiology in the Department of Epidemiology and Public Health at the Yale School of Public Health and Yale School of Medicine, in an interview with Epoch TV’sAmerican Thought Leaders.
It’s anatomic pathologists who receive the biopsies and analyze them to diagnose the cancer. Thus, they are on the front lines of seeing an increased number of biopsies for younger patients showing up with the types of cancers that normally take many years to grow large enough to be discovered by imaging and lumps leading to biopsy and diagnosis. It’s a medical mystery that may have long term effects on younger populations.
“What clinicians have been seeing is very strange things,” said Harvey Risch, MD, PhD (above), Professor Emeritus of Epidemiology at the Yale School of Public Health and Yale School of Medicine, in an Epoch TV interview. “For example, 25-year-olds with colon cancer, who don’t have family histories of the disease—that’s basically impossible along the known paradigm for how colon cancer works—and other long-latency cancers that they’re seeing in very young people.” Epidemiologists and anatomic pathologists are describing these conditions as “turbo cancers.” (Photo copyright: Yale University.)
Early-Onset Cancer Rates Jump Sharply
According to the federal Centers for Disease Control and Prevention (CDC), about 3.3 million Americans died in 2022, and 607,800 of those deaths were attributed to cancer. This statistic translates to approximately 18.4% of US deaths being due to cancer last year.
An article published in the Journal of the American Medical Association titled, “Patterns in Cancer Incidence among People Younger than 50 Years in the US, 2010 to 2019,” states that the rates of cancer in people under the age of 50 has risen sharply in recent years. The study found that “the incidence rates of early-onset cancer increased from 2010 to 2019. Although breast cancer had the highest number of incident cases, gastrointestinal cancers had the fastest-growing incidence rates among all early-onset cancers.”
The largest increase in cancer diagnoses occurred in people in the 30 to 39-year-old age group. This number represents a jump of almost 20% for the years analyzed for individuals in that demographic. The researchers also found that cancer rates decreased in individuals over the age of 50.
Breast cancer, which increased by about 8% in younger people, accounted for the most diagnoses in this age group. However, the biggest increase was 15% for gastrointestinal cancers, including colon, appendix, bile duct, and pancreatic cancer.
Because cancer can recur or progress, researchers have concerns about what happens to young cancer patients as they grow older and what effect cancer may have on their lives.
“They are at a transitional stage in life,” Chun Chao, PhD, Research Scientist, Division of Epidemiologic Research at Kaiser Permanente, told The Hill. “If you think about it, this is the age when people are trying to establish their independence. Some people are finishing up their education. People are trying to get their first job, just start to establish their career. And people are starting new families and starting to have kids. So, at this particular age, having a cancer diagnosis can be a huge disruption to these goals.”
Sadly, young cancer survivors have a heightened risk of developing a second cancer and a variety of other health conditions, such as cardiovascular diseases and metabolic disorders.
Lifestyle a Factor in Increased Risk for Cancer
“The increase in early-onset cancers is likely associated with the increasing incidence of obesity as well as changes in environmental exposures, such as smoke and gasoline, sleep patterns, physical activity, microbiota, and transient exposure to carcinogenic compounds,” according to the JAMA study.
“Suspected risk factors may involve increasing obesity among children and young adults; also the drastic change in our diet, like increasing consumption of sugar, sweetened beverages, and high fat,” Hyuna Sung, PhD, Cancer Surveillance Researcher at the American Cancer Society, told US News and World Report. “The increase in cancers among young adults has significant implications. It is something we need to consider as a bellwether for future trends.”
“Increased efforts are required to combat the risk factors for early-onset cancer, such as obesity, heavy alcohol consumption, and smoking,” said Daniel Huang, MD, Assistant Professor of Medicine at the National University of Singapore, one of the authors of the study, in the US News and World Report interview.
Other studies also have shown a rise in so-called turbo cancers.
“Cancer as a disease takes a long time to manifest itself from when it starts. From the first cells that go haywire until they grow to be large enough to be diagnosed, or to be symptomatic, can take anywhere from two or three years for the blood cancers—like leukemias and lymphomas—to five years for lung cancer, to 20 years for bladder cancer, or 30 to 35 years for colon cancer, and so on,” Risch told the Epoch Times.
Not the Occurrence Oncologists Expect
“Some of these cancers are so aggressive that between the time that they’re first seen and when they come back for treatment after a few weeks, they’ve grown dramatically compared to what oncologists would have expected,” Risch continued. “This is just not the normal occurrence of how cancer works.”
Risch believes that damage to the immune system is the most likely cause of the rise in turbo cancers. He said the immune system usually recognizes, manages, and disables cancer cells so they cannot progress. However, when the immune system is impaired, cancer cells can multiply to the point where the immune system cannot cope with the number of bad cells.
It is a statistical fact that more people are being diagnosed with serious cases of cancer at younger and younger ages. If this trend continues, clinical laboratories and pathologists can expect to see more oncology case referrals and perform more cancer diagnostic tests for younger patients.
HIMSS names SMC a ‘world leader’ in digital pathology and awards the South Korean Healthcare provider Stage 7 DIAM status
Anatomic pathologists and clinical laboratory managers in hospitals know that during surgery, time is of the essence. While the patient is still on the surgical table, biopsies must be sent to the lab to be frozen and sectioned before going to the surgical pathologist for reading. Thus, shortening time to answer for frozen sections is a significant benefit.
This effort in surgical pathology is part of a larger story of the digital transformation underway across all service lines at this hospital. For years, SMC has been on track to become one of the world’s “intelligent hospitals,” and it is succeeding. In February, SMC became the first healthcare provider to achieve Stage 7 in the HIMSS Digital Imaging Adoption Model (DIAM), which “assesses an organization’s capabilities in the delivery of medical imaging,” Healthcare IT News reported.
As pathologists and clinical laboratory leaders know, implementation of digital pathology is no easy feat. So, it’s noteworthy that SMC has brought together disparate technologies to reduce turnaround times, and that the medical center has caught the eye of leading health information technology (HIT) organizations.
“The digital pathology system established by the pathology department and SMC’s information strategy team could be one of the good examples of the fourth industrial revolution model applied to a hospital system,” anatomic pathologist Kee Taek Jang, MD (above), Professor of Pathology, Sungkyunkwan University School of Medicine, Samsung Medical Center told Healthcare IT News. Clinical laboratory leaders and surgical pathologists understand the value digital pathology can bring to faster turnaround times. (Photo copyright: Samsung Medical Center.)
Anatomic Pathologists Can Read Frozen Sections on Their Smartphones
Prior to implementation of its 5G digital pathology system, surgeons and their patients waited as much as 20 minutes for anatomic pathologists to traverse SMC’s medical campus to reach the healthcare provider’s cancer center diagnostic reading room, Healthcare IT News reported.
Now, SMC’s integrated digital pathology system—which combines slide scanners, analysis software, and desktop computers with a 5G network—has enabled a “rapid imaging search across the hospital,” Healthcare IT News noted. Surgical pathologists can analyze tissue samples faster and from remote locations on digital devices that are convenient to them at the time, a significant benefit to patient care.
“The system has been effective in reducing the turnaround time as pathologists can now attend to frozen test consultations on their smartphone or tablet device via 5G network anywhere in the hospital,” Jean-Hyoung Lee, SMC’s Manager of IT Infrastructure, told Healthcare IT News which noted these system results:
TAT decreased from 20 minutes to 10 minutes.
Transferring scans of large frozen tissues up to three gigabyte in size is now possible through the 5G network.
Additionally, through the 5G network, pathologists can efficiently access CT scans and MRI data on proton therapy cancer treatments. Prior to the change, the doctors had to download the image files in SMC’s Proton Therapy Center, according to a news release from KT Corporation, a South Korean telecommunications company that began working with SMC on building the 5G-connected digital pathology system in 2019.
DIAM is an approach for gauging an organization’s medical imaging delivery capabilities. To achieve Stage 7—External Image Exchange and Patient Engagement—healthcare providers must also have achieved all capabilities outlined in Stages 5 and 6.
In addition, the following must also have been adopted:
The majority of image-producing service areas are exchanging and/or sharing images and reports and/or clinical notes based on recognized standards with care organizations of all types, including local, regional, or national health information exchanges.
The application(s) used in image-producing service areas support multidisciplinary interactive collaboration.
Patients can make appointments, and access reports, images, and educational content specific to their individual situation online.
Patients are able to electronically upload, download, and share their images.
“This is the most comprehensive use of integrated digital pathology we have seen,” Andrew Pearce, HIMSS VP Analytics and Global Advisory Lead, told Healthcare IT News.
SMC’s Manager of IT Planning Seungho Lim told Healthcare IT News the medical center’s goal is to become “a global advanced intelligent hospital through digital health innovation.” The plan is to offer, he added, “super-gap digital services that prioritize non-contact communication and cutting-edge technology.”
For pathologists and clinical laboratory leaders, SMC’s commitment to 5G to move digital pathology data is compelling. And its recognition by HIMSS could inspire more healthcare organization to make changes in medical laboratory workflows. SMC, and perhaps other South Korean healthcare providers, will likely continue to draw attention for their healthcare IT achievements.
Google designed the suite to ease radiologists’ workload and enable easy and secure sharing of critical medical imaging; technology may eventually be adapted to pathologists’ workflow
Clinical laboratory and pathology group leaders know that Google is doing extensive research and development in the field of cancer diagnostics. For several years, the Silicon Valley giant has been focused on digital imaging and the use of artificial intelligence (AI) algorithms and machine learning to detect cancer.
Now, Google Cloud has announced it is launching a new medical imaging suite for radiologists that is aimed at making healthcare data for the diagnosis and care of cancer patients more accessible. The new suite “promises to make medical imaging data more interoperable and useful by leveraging artificial intelligence,” according to MedCity News.
In a press release, medical technology company Hologic, and healthcare provider Hackensack Meridian Health in New Jersey, announced they were the first customers to use Google Cloud’s new suite of medical imaging products.
“Hackensack Meridian Health has begun using it to detect metastasis in prostate cancer patients earlier, and Hologic is using it to strengthen its diagnostic platform that screens women for cervical cancer,” MedCity News reported.
“Google pioneered the use of AI and computer vision in Google Photos, Google Image Search, and Google Lens, and now we’re making our imaging expertise, tools, and technologies available for healthcare and life sciences enterprises,” said Alissa Hsu Lynch (above), Global Lead of Google Cloud’s MedTech Strategy and Solutions, in a press release. “Our Medical Imaging Suite shows what’s possible when tech and healthcare companies come together.” Clinical laboratory companies may find Google’s Medical Imaging Suite worth investigating. (Photo copyright: Influencive.)
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Easing the Burden on Radiologists
Clinical laboratory leaders and pathologists know that laboratory data drives most healthcare decision-making. And medical images make up 90% of all healthcare data, noted an article in Proceedings of the IEEE (Institute of Electrical and Electronics Engineers).
More importantly, medical images are growing in size and complexity. So, radiologists and medical researchers need a way to quickly interpret them and keep up with the increased workload, Google Cloud noted.
“The size and complexity of these images is huge, and, often, images stay sitting in data siloes across an organization,” said Alissa Hsu Lynch, Global Lead, MedTech Strategy and Solutions at Google, told MedCity News. “In order to make imaging data useful for AI, we have to address interoperability and standardization. This suite is designed to help healthcare organizations accelerate the development of AI so that they can enable faster, more accurate diagnosis and ease the burden for radiologists,” she added.
According to the press release, Google Cloud’s Medical Imaging Suite features include:
Imaging Storage: Easy and secure data exchange using the international DICOM (digital imaging and communications in medicine) standard for imaging. A fully managed, highly scalable, enterprise-grade development environment that includes automated DICOM de-identification. Seamless cloud data management via a cloud-native enterprise imaging PACS (picture archiving and communication system) in clinical use by radiologists.
Imaging Lab: AI-assisted annotation tools that help automate the highly manual and repetitive task of labeling medical images, and Google Cloud native integration with any DICOMweb viewer.
Imaging Datasets and Dashboards: Ability to view and search petabytes of imaging data to perform advanced analytics and create training datasets with zero operational overhead.
Imaging AI Pipelines: Accelerated development of AI pipelines to build scalable machine learning models, with 80% fewer lines of code required for custom modeling.
Imaging Deployment: Flexible options for cloud, on-prem (on-premises software), or edge deployment to allow organizations to meet diverse sovereignty, data security, and privacy requirements—while providing centralized management and policy enforcement with Google Distributed Cloud.
First Customers Deploy Suite
Hackensack Meridian Health hopes Google’s imaging suite will, eventually, enable the healthcare provider to predict factors affecting variance in prostate cancer outcomes.
“We are working toward building AI capabilities that will support image-based clinical diagnosis across a range of imaging and be an integral part of our clinical workflow,” said Sameer Sethi, Senior Vice President and Chief Data and Analytics Officer at Hackensack, in a news release.
The New Jersey healthcare network said in a statement that its work with Google Cloud includes use of AI and machine learning to enable notification of newborn congenital disorders and to predict sepsis risk in real-time.
Hologic, a medical technology company focused on women’s health, said its collaboration integrates Google Cloud AI with the company’s Genius Digital Diagnostics System.
“By complementing our expertise in diagnostics and AI with Google Cloud’s expertise in AI, we’re evolving our market-leading technologies to improve laboratory performance, healthcare provider decision making, and patient care,” said Michael Quick, Vice President of Research and Development and Innovation at Hologic, in the press release.
Hologic says its Genius Digital Diagnostics System combines AI with volumetric medical imaging to find pre-cancerous lesions and cancer cells. From a Pap test digital image, the system narrows “tens of thousands of cells down to an AI-generated gallery of the most diagnostically relevant,” according to the company website.
Hologic plans to work with Google Cloud on storage and “to improve diagnostic accuracy for those cancer images,” Hsu Lynch told MedCity News.
Medical image storage and sharing technologies like Google Cloud’s Medical Imaging Suite provide an opportunity for radiologists, researchers, and others to share critical image studies with anatomic pathologists and physicians providing care to cancer patients.
One key observation is that the primary function of this service that Google has begun to deploy is to aid in radiology workflow and productivity, and to improve the accuracy of cancer diagnoses by radiologists. Meanwhile, Google continues to employ pathologists within its medical imaging research and development teams.
Assuming that the first radiologists find the Google suite of tools effective in support of patient care, it may not be too long before Google moves to introduce an imaging suite of tools designed to aid the workflow of surgical pathologists as well.
