Researchers have discovered a blood protein that could be used as a marker for stomach and other cancers that is more accurate than existing diagnostic biomarkers, even in the early stages of the disease. This simple test may lead to earlier diagnosis of often silent gastrointestinal cancers.
Gastrointestinal cancers include esophageal, stomach, colorectal, liver and pancreatic cancers, which often go undetected. Late detection of these cancers affects treatment effectiveness and leads to increased mortality.
While there are biomarkers for detecting cancer, they may not be accurate, do not always detect all types of cancer, or their measurement technology is complex and expensive. Researchers at Nagoya University have discovered a protein that is a reliable marker of stomach cancer, detectable even in the early stages of the disease and requiring only a simple blood test.
Takahiro Shinozuka, first author of the study, said: "Currently, blood tests to detect cancers such as gastric, colorectal, and breast cancer use tumor markers such as CEA and CA19-9. However, these tumor markers do not always accurately detect all cancers, and their accuracy needs to be improved. Other markers have been proposed, but these have several disadvantages, such as complex and expensive measurement procedures or invasive detection methods, which have hindered their use."
Carcinoembryonic antigen (CEA) is produced by colorectal cancer cells and released into the blood. However, not all colorectal cancers produce carcinoembryonic antigen, so normal levels do not necessarily rule out cancer. CEA levels are also elevated in patients with breast, lung, and thyroid cancer, and in non-cancer patients such as liver disease, pancreatitis, and ulcerative colitis. Meanwhile, carbohydrate antigen 19-9 (CA19-9) is released by pancreatic, gallbladder, lung, and colon cancer cells, but diabetes, pancreatitis, and other lung, urinary, and gynecological diseases can also cause elevated levels of CA19-9.
Using a gastric cancer cell line, the researchers identified a new diagnostic biomarker detectable in the blood using a previously reported secretome (proteins expressed by cells, tissues and organs) dataset. They found that stromal cell-derived factor 4 (SDF4) is a potential serum tumor diagnostic marker.
They collected blood samples from 582 patients with gastric, breast, colorectal, pancreatic, esophageal and liver cancer and 80 healthy controls and found that SDF4 was consistently elevated in the cancer samples. In patients with gastric cancer, SDF4 levels increased with clinical stage, and patients with stage I gastric cancer had significantly higher SDF4 levels compared with healthy controls, suggesting that the test can detect gastric cancer early before symptoms appear.
The researchers found that as a biomarker for gastric cancer, SDF4 had a sensitivity of 89% and a specificity of 99%. Sensitivity indicates the test's ability to detect the disease in people who have the disease, while specificity refers to the test's ability to identify people who do not have the disease. Highly sensitive testing means false negative results are rare. In terms of sensitivity, SDF4 outperformed existing cancer biomarkers: 13% for CEA and 17% for CA19-9.
The researchers acknowledged that a major limitation of the study is that the sample size was small and, from a single institution in Japan, may not be representative of other patient populations. Future studies using larger cohorts are necessary to determine the diagnostic significance of SDF4 and to apply the findings to clinical practice. However, they see potential in using SDF4 as a diagnostic marker for gastric and other cancers.
"As a diagnostic marker, SDF4 is superior to traditional tumor markers in two aspects. First, it can diagnose early-stage cancer patients; second, it can be used as a diagnostic marker for various cancers. We are working with a company to develop measurement devices that can be used for cancer screening. If these efforts are successful, we hope to introduce SDF4 into actual cancer screening to help detect cancer early," Shinozuka said.
The research was published in the journal Scientific Reports.