New protein may help to catch lung cancer early

Researchers may have found a biomarker for lung cancer, which could soon enable healthcare professionals to detect the disease while it is still in stage 1.

Lung cancer is the second most prevalent form of cancer in men and women and the top cancer killer among both sexes.

The American Cancer Society (ACS) estimate that in 2018, 154,050 people in the United States will have died from the disease.

The World Health Organization (WHO) suggest that 1.69 million deaths are brought about by lung cancer worldwide.

The main reason behind why lung cancer has such a high mortality rate is that it is often caught at an advanced stage.

In fact, around three quarters of people with lung cancer already experience symptoms when they present themselves for a checkup, and, by that point, cancer has usually already spread to other parts of the lungs or elsewhere in the body.

"The identification of patients at an early stage of cancer when it can be treated surgically," states Yuichi Sato, of the Department of Molecular Diagnostics at the Kitasato University School of Allied Health Sciences in Kanagawa, Japan, "is extremely important to improve prognosis."

"We need better biomarkers for early diagnosis," adds Sato, who led a new study that identified a protein that may help to diagnose lung cancer while it is still in stage 1.

According to the ACS, the survival rate for individuals whose lung cancer is diagnosed at stage 1 ranges between 68 and 92 percent.

The new protein is called cytoskeleton-associated protein 4 (CKAP4), and its potential as a lung cancer biomarker is detailed in The American Journal of Pathology.

CKAP4 is better than current biomarkers

To develop a marker for cancer, Sato and colleagues developed a so-called monoclonal antibody — that is, a type of antibody used to fight cancer in immunotherapy.

Monoclonal antibodies work by recognizing certain proteins on cells. In this study, the researchers used the antibody called KU-Lu-1 to see whether or not it would recognize cancer proteins in the blood of 271 people with lung cancer.

They also studied the behavior of KU-Lu-1 in the blood of 100 healthy people. The antibody detected CKAP4 in lung cancer tissue and tumor cells.

Sato and team explain the significance of their findings, emphasizing the place of CKAP4 among existing biomarkers for lung cancer.

Study co-author Ryo Nagashio — also affiliated with the Kitasato University School of Allied Health Sciences — explains that the four main biomarkers currently used to detect lung cancer are:

  • carcinoma embryonic antigen (CEA)
  • sialyl Lewis X antigen
  • squamous cell carcinoma antigen (SCCA)
  • cytokeratin fragment (CYFRA) 21-1

But none of these are sensitive enough to detect cancer in its first stages, he says. CEA, CYFRA, and SCCA are known to have the following sensitivities, respectively: 30–52 percent, 17–82 percent, and 24–39 percent.

The sensitivity of a diagnostic biomarker refers to the percentage of cases it manages to detect out of the total number of people who have the disease.

Using machine learning algorithms, the scientists found that CKAP4 proved a sensitivity between 69 and 81 percent.

Crucially, the biomarker sensitivity remained high even in stage 1 lung cancer, meaning that CKAP4 blood levels were high in people with this early stage of the disease.

"The results of our study provide evidence that the CKAP4 protein may be a novel early sero-diagnostic marker for lung cancer," concludes Nagashio.

"The use of CKAP4 as a biomarker could change current practices regarding the treatment of lung cancer patients, and the diagnostic accuracies may be markedly improved by the combination of CKAP4 and conventional markers."

Yuichi Sato