have found significantly higher levels of cytoskeleton-associated protein 4
(CKAP4) in the blood of patients with lung cancer than in healthy individuals
- Novel biomarker (CKAP4)
that is detected as early as in stage 1 non-small-cell lung
cancer and squamous cell carcinoma now identified.
- Poor prognosis of lung cancer is mainly due to
the late diagnosis of the disease.
- Using a combination of CKAP4 and conventional markers for early
diagnosis could markedly improve diagnostic accuracies and change current
practices regarding the treatment of lung cancer patients.
Moreover, the protein is sensitive enough to be detected in the patients' blood
as early as in stage I of non-small-cell lung cancer and squamous cell
carcinoma, compared to current biomarkers. This could potentially make it a
non-invasive diagnostic marker for specific lung cancers to be used for early
detection and to improve patient outcomes.
"The identification of patients
at an early stage of cancer when it can be treated surgically is extremely
important to improve prognosis," explained Yuichi Sato, PhD, Department of
Molecular Diagnostics, Kitasato University School of Allied Health Sciences, Sagamihara,
Kanagawa, Japan, who led the study. "We need better biomarkers for early
‘Scientists have now identified a new biomarker called CKAP4 that can be detected at the stage 1 level of the disease; this could change current practices in the diagnosis and treatment of some types of lung cancer and improve patient outcomes.’
The findings are published in The American Journal of Pathology
protein 4 (CKAP4) or
CLIMP-63 (cytoskeleton-linking membrane protein 63)
apart from playing an essential role in the maintenance of the endoplasmic
reticulum structure has more recently been identified as a cell surface receptor for four unique extracellular ligands
(substances that bind to biomolecules to serve a biological function); these
are tissue plasminogen activator, surfactant protein A, Dickkopf1 (DKK1)
, and antiproliferative factor.
CKAP4 has also been described as a
marker in different cancers.
Recently, simultaneous expressions of DKK1 and CKAP4 were frequently observed
in tumor lesions of human pancreatic and lung
, and it was noted that if the levels of the co-expressed
proteins in tumor tissues were less, then there was better prognosis and
relapse-free survival in the patients.
Current Biomarkers for Lung Cancer
biomarkers used in detecting lung cancer up until now are not sensitive enough
to detect tumors at an early stage; these include carcinoma embryonic
antigen (CEA), sialyl Lewis X antigen (SLX), squamous cell carcinoma (SCC)
antigen, and cytokeratin fragment (CYFRA) 21-1. Across various stages of the
disease (I-IV), the sensitivities of
serum CEA, CYFRA, and SCCA are reported as 30 to 52, 17 to 82, and 24 to 39
. Sensitivity denotes the fraction of people who have
the disease and who test positive. A perfect diagnostic marker will show 100% sensitivity, i.e., all patients with the disease
will be detected.
Study - Detection of high levels of CKAP4 in lung
- Two hundred and seventy one lung cancer patients
and hundred healthy individuals were chosen for the study.
- Blood taken from the individuals were analyzed
using a reverse-phase protein array
(RPPA) analysis machine that measures protein expression levels in a
large number of biological samples using validated high-quality
- For this particular experiment, the monoclonal
antibody used was called KU-Lu-1
which reacted only with tumor cells and tumor stromal fibroblasts and not
with normal lung tissues. The crosstalk between stromal cells and cancer
cells is highly responsible for the progression of tumors and their metastasis.
- The researchers confirmed that the KU-Lu-1
antibody recognized CKAP4 in lung cancer cells and tissues using immunoprecipitation
and mass spectrometry.
- The investigators also studied a validation set
that consisted of samples from 100 patients with lung cancer and 38
of the study
- Serum CKAP4 had a
sensitivity of 81 percent in the training set and 69 percent in the
validation set; these rates were higher than those of the current
- The sensitivity of serum
CKAP4 was high even when measured in stage I non-small-cell lung cancer
and squamous cell carcinoma.
"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," concluded Dr. Sato.
cancer is one of the most common cancers in the world and one that leads to the
most number of cancer deaths. Cigarette smoking is the greatest risk factor for
lung cancer, followed by pollution, radiation and asbestos exposure.
Common symptoms are a persistent
cough that progressively worsens over time, constant chest pain, coughing up
blood, shortness of breath and repeated pneumonia or bronchitis
Diagnosing lung cancer at an
advanced stage is the main reason for the poor outcome of the disease.
- Lung Cancer - (https://medlineplus.gov/lungcancer.html)
- Kengo Yanagita, Ryo Nagashio, Shi-Xu Jiang, Yuki Kuchitsu, Kazuo Hachimura, Masaaki Ichinoe, Satoshi Igawa, Eriko Fukuda, Naoki Goshima,
Yukitoshi Satoh, Yoshiki Murakumo, Makoto Saegusa, Yuichi Sato. "Cytoskeleton-Associated Protein 4 Is a Novel Serodiagnostic Marker for Lung Cancer", American
Journal of Pathology (2018) https://doi.org/10.1016/j.ajpath.2018.03.007