Autoantibody Panel Differentiates Lung Cancer From Benign Nodules

A set of autoantibodies was found to be associated with lung adenocarcinoma when compared to smoker control patients, according to a new study. A separate autoantibodies set also can differentiate lung cancer from benign nodules that return a positive CT scan test, offering a potential way to reduce CT scan false positives.

Early detection of lung cancer with molecular biomarkers is difficult because of their very low concentration in blood; detecting the presence of tumor cells based on the immune response represents an alternative strategy. “These responses of the adaptive immune system against target tumor antigens effectively amplify the signals from the minute amount of tumor proteins released from cancer tissue,” wrote study authors led by Jie Wang, PhD, of Arizona State University in Tempe.

The new study had several steps. First, researchers profiled seroreactivity to 10,000 full-length proteins in both 40 patients with early-stage lung cancer and in 40 smoker controls. From that, 17 promising antigens were identified and tested further using enzyme-linked immunosorbent assays in 137 cancer patients and 127 smoker controls.

The result was a five-autoantibody classifier assay that could differentiate lung cancer patients from the smoker controls with a sensitivity of 30% and a specificity of 89%. The included autoantibodies were tetratricopeptide repeat domain 14 (TTC14); B-Raf proto-oncogene, serine/threonine kinase (BRAF); actin like 6B (ACTL6B); MORC family CW-type zinc finger 2 (MORC2); and cancer/testis antigen 1B (CTAG1B). Alone, each of those autoantibodies had a specificity of 97.6% and a sensitivity ranging from 5.1% to 12.4%.

A separate set of autoantibodies was found to differentiate between lung cancer patients and a set of 170 patients with CT-positive benign nodules. These included keratin 8, type II (KRT8); TTC14; Kruppel-like factor 8 (KLF8); BRAF; and tousled like kinase 1 (TLK1). This panel had a sensitivity of 30% and specificity of 88% to differentiate between the lung cancer and benign nodule patients.

There was no difference between those deemed autoantibody responders and non-responders with regard to known clinical risk factors including sex, age, or smoking history. The authors wrote that this suggests the autoantibody panel offers information beyond known risk factors.

“The [autoantibody] markers reported in this study are still limited in their sensitivity,” they wrote. “It will be useful in the future to combine these markers with other existing markers to create a panel with better distinguishing characteristics. In the future, we will be focusing on combining existing markers with our panel to achieve higher sensitivity.” Using longitudinal samples to track changes in antibody expression could also be useful in developing the assay.