LINE-1-ORF1p Is a Promising Biomarker for Early Cancer Detection, But More Research Is Needed

Amanda Brink, DNP, APRN, FNP-BC, AOCNP

Imagine learning about a groundbreaking serum biomarker that has the potential to revolutionize the early detection of cancer. Would you be open to undergoing such a test? Personally, I'm inclined to say yes. This innovative approach could motivate me to ensure that my cancer screenings are up to date and empower me to proactively manage my healthcare. It's not just a test; it's a step towards more effective early detection and prevention.

A variety of biomarkers are available to assist in detecting, stratifying the risk, and monitoring patients undergoing cancer treatment. Oncology nurses are familiar with tumor marker biomarkers, such as cancer antigen 125 (CA-125), which is often elevated in gynecologic cancers, and carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA), which are often elevated in gastrointestinal malignancies, among others. However, despite their use in patients with a confirmed cancer diagnosis, these tumor markers are often non-specific and not always helpful in early cancer detection. Even in patients with a known malignancy who commonly produce these proteins, tumor markers may not be elevated in all patients, particularly in the early stages of their cancer treatment journey. Consequently, healthcare professionals and researchers are consistently searching for alternative non-invasive tests for the early detection of cancer.

Highlighting a Potential New Serum Biomarker: LINE-1-ORF1p

Long interspersed element-1 (LINE-1) open reading frame 1 protein (ORF1p) is a protein found to be overexpressed in cancer and high-risk cancer precursors, such as Barrett’s esophagus, a condition associated with a heightened risk of developing esophageal cancer, with minimal expression in normal tissue. ORF1p is particularly prevalent in solid tumors including esophageal, colorectal, lung, breast, prostate, ovarian, endometrial, pancreatic, and head and neck cancers. Consequently, ORF1p may serve as a highly specific serum biomarker for multiple types of common cancers, as outlined in a recent article in Cancer Discovery.¹

While ORF1p is easily detectable in tumor tissue (found in up to 91% of colorectal cancer tumors, for example), its presence in the blood is limited to low concentrations, posing a challenge for conventional clinical laboratories. Therefore, the authors employed a more sensitive test known as Single Molecule Array to detect ORF1p in the blood.

Investigators tested the blood of patients with cancer as well as the blood of over 400 “healthy” individuals as controls. Patients ages ranged from 20 to 90 years. ORF1p was undetectable in approximately 99% of the controls. Among the 5 control patients with detectable ORF1p, the individual with the highest result was diagnosed with advanced prostate cancer 6 months after the ORF1p testing and cutaneous T cell lymphoma 19 months later. As of now, it is unknown whether any of the other 4 healthy controls have been diagnosed with cancer or a high-risk cancer precursor.

In patients with a known cancer diagnosis who were tested for ORF1p in the blood, the highest proportion of positive cases was observed in patients with colorectal cancer (58%, n = 101) and ovarian cancer (71%, n = 145). While many patients presented with advanced disease, some with detectable ORF1p were still in the early stages, including 4 out of 8 patients with stage I ovarian cancer.

The authors also tested 30 patients with chronic liver disease, and the 1 patient who tested positive was later diagnosed with hepatocellular carcinoma.

Patients with systemic lupus erythematosus (SLE) were also tested because individuals with autoimmune disorders are known to produce antibodies against ORF1p. None of the patients with SLE were found to have detectable levels of ORF1p.

Nursing Considerations

Patients, including those without a known cancer diagnosis, may come across information about testing for ORF1p in the news and be curious about how to undergo this test. However, since ORF1p as a biomarker is still in the early stages of development, it is not widely available for routine testing. Nurses would need to explain to patients that additional research is necessary with larger cohorts of patients to further validate the study authors’ findings. Furthermore, the authors have only studied patients with solid tumor carcinomas and have not yet investigated patients with other cancer types, such as hematologic malignancies.

The cost of any new technology is also a consideration. While the study authors indicate that the tests used in this study are cost-effective, rapid, and simple to perform, additional clarification is needed regarding how this testing could be made available in other laboratories in the future. It is possible that a patient’s sample would need to be sent to an outside lab for testing, and results may not be readily available from any hospital lab.

I reaffirm my sentiments from the opening paragraph of this article. I hope that, in the future, we can employ ORF1p testing, among other tests, to aid in the early detection of cancer when it is most treatable. There is ongoing work to validate this test, and I appreciate the efforts of researchers, such as the study authors highlighted here, who are instrumental in leading the way.

Reference

Taylor MS, Wu C, Fridy PC, et al. Ultrasensitive detection of circulating LINE-1 ORF1p as a specific multi-cancer biomarker. Published online September 12, 2023. Cancer Discov. doi:10.1158/2159-8290.CD-23-0313