GASTROClear is the world’s first molecular blood test for early detection of gastric cancer in high-risk populations.
The GASTROClear test provides information to help doctors identify patients who may benefit from detailed medical examinations to diagnose gastric cancer early, before symptoms appear.
The science behind
The test measures a panel of 12 microRNA biomarkers which has been shown to detect 87% of all gastric cancers, including up to 89% of early-stage (stage 1-2) gastric cancers.. The expression levels of these 12 microRNAs are translated into a risk score calculated by a clinically validated proprietary algorithm. Based on risk scores, patients are classified as high risk, intermediate risk, or low risk, with specific follow-up recommendations for doctors in managing each group.
The benefits of using GASTROClear
The GASTROClear, an in-vitro diagnostic medical device (IVD), is intended for use as an adjunctive test for the detection of gastric neoplasia associated miRNA biomarkers in human serum. GASTROClear is NOT intended as a replacement for gastroscopy; it should be used in conjunction with gastroscopy and other test methods in accordance with recognised clinical guidelines. It is thus an adjective tool to aid in the detection of gastric cancer.
As such, only patients who met certain criteria are tested using GASTROClear. The result obtained from the test may indicate the presence of gastric cancer and the patient then goes for gastroscopy and biopsy as required. The output of the GASTROClear test is a risk score where a high score may indicate the presence of gastric cancer and should be followed up by gastroscopy.
This test is intended for adults of either sex, 40 years or older at average risk of having gastric cancer with one of the following risk factors:
- Frozen serum: 200µl per patient per run
- Both PCR Instruments below are required:
Applied Biosystems Veriti Dx 96-well Thermocycler instrument model 9912, with 0.2 ml sample wells (catalog no: 4452300).
Applied Biosystems QuantStudio Dx 384W Real-Time PCR Instrument with the QuantStudio Dx Software (catalog no: 4479890).
for healthcare professionals
GASTROClear is the world’s first molecular blood test approved for use in early detection of gastric (stomach) cancer. It is an in vitro diagnostic (IVD) test intended to be used in conjunction with gastroscopy for detection of gastric cancer.
No. GASTROClear is an adjunctive test that is intended to be used in conjunction with gastroscopy and other test methods in accordance with recognized clinical guidelines. It is NOT intended as a replacement for gastroscopy.
No. GASTROClear is not indicated for use as a standalone diagnostic test. Gastric cancer is clinically diagnosed through gastroscopy or imaging tests like barium X-ray or CT scan, and histopathological examination.
As an in vitro diagnostic test, GASTROClear is intended for adults of either sex, 40 years or older at average risk of having gastric cancer with any one of the following risk factors:
- Family history of gastric cancer.
- A history of Helicobacter pylori (H. pylori) infection.
- Previous history of stomach lymphoma and stomach polyps.
- Long term stomach inflammation (chronic gastritis).
- Diets containing large amounts of fried food, smoked foods, salted fish, processed meat, and pickled foods.
- Diets containing nitrites and nitrate substances commonly found in cured meats.
- Diet low in fruits and vegetables.
GASTROClear has been verified to have 82% sensitivity and 88% specificity for detecting gastric cancer in an asymptomatic, average-risk Chinese and Korean population.
In a symptomatic, high-risk Singaporean population, GASTROClear had sensitivities of 87.5% for stage I and 89.5% for stage II gastric cancer, at 68.4% specificity.
The purpose of screening is to detect gastric cancer, if any, at an early stage so that treatment can begin as soon as possible, thus improving the chances of survival.
Gastric cancer is the second leading cause of death in the world. East Asian countries account for about half of the world’s gastric cancer incidence, and mortality is much higher than other countries and regions. Japan and South Korea have significantly reduced deaths caused by gastric cancer through national screening programmes for gastric cancer. Gastric cancer is one of the most lethal cancer types because most gastric cancers are diagnosed in the advanced stage, when the tumour cannot be surgically removed. Even if they can be surgically removed, the 5-year survival rate is less than 30%. Early stage gastric cancer can be surgically resected with a good prognosis. The 5-year survival rate is more than 90% for early gastric cancers treated with surgery. Gastric cancer causes no symptoms or mild symptoms in the early stage and is very easily overlooked. More than 70% of gastric cancers in Singapore are detected in the late stages. Therefore, early screening can lead to early detection of gastric cancer and this can effectively improve gastric cancer patient survival.
The GASTROClear test detects multiple microRNA (miRNA) biomarkers associated with gastric cancer. The quantities of 12 miRNAs are measured to provide an additive association with gastric cancer. The result from the test may indicate the presence of gastric cancer and the patient then goes for gastroscopy and biopsy as required. The output of the GASTROClear test is a risk score where a high score may indicate the presence of gastric cancer and should be followed up by gastroscopy.
microRNAs or miRNAs are biological molecules that have important regulatory functions in normal human cells. However, because they are important for normal functioning of the human body, abnormalities affecting the quantities of miRNAs in the body can lead to many diseases such as cancer.
Cancer patients have changes in miRNA composition and quantities compared to healthy individuals. Differences in miRNA profiles have been observed in different cancer types and in different stages of the same cancer. Healthy people have a healthy miRNA signature while people with gastric cancer have a gastric cancer-associated miRNA signature that we have identified through years of research starting in 2012. From this research, we developed the GASTROClear panel of 12 miRNA markers that can be used for accurate detection of gastric cancer. We have evidence from large-scale clinical validation studies that GASTROClear can accurately assess a person’s risk of having gastric cancer at the time when blood is drawn for the test.
The miRNAs detected may be secreted into a patient’s blood by cancer cells or by other cells affected by the cancer. These gastric cancer-associated miRNAs may be involved in the process of gastric cancer formation. For example, they may have functions in regulating inflammation, proliferation, invasion, and angiogenesis. We can assess the risk that a patient may have a gastric tumour in your body by measuring the quantities of these miRNAs in the patient’s blood.
GASTROClear uses a RT-qPCR (reverse transcription quantitative polymerase chain reaction) technology with a highly-controlled workflow to detect and quantify miRNAs.
Some of these miRNAs were shown to promote cancer metastasis and modulate tumor immune environment but additional research studies are required to elucidate their roles in gastric cancer development and progression.
The clinical studies pertaining to the development and validation of the GASTROClear test have been peer-reviewed and published in Gut, a leading international medical journal. The scientific paper can be accessed here:
GASTROClear was developed by an international team comprising clinicians and researchers from the Singapore Gastric Cancer Consortium, the Agency for Science, Technology and Research (A*STAR), National University Hospital (NUH), Tan Tock Seng Hospital (TTSH), Yonsei Cancer Center, and MiRXES.
GASTROClear has been approved for in vitro diagnostic use by the Health Sciences Authority. It has been included in the Singapore Medical Device Register since May 2019:
There are currently no MOH recommendations for gastric cancer screening in Singapore. The only countries that have currently implemented national gastric cancer screening using gastroscopy and/or X-ray are Japan and Korea which have high incidence of gastric cancer. GASTROClear is designed as an adjunctive test to identify high-risk individuals for gastroscopy screening, as a cost-effective strategy of mass screening in countries like Singapore which have intermediate to high gastric cancer incidence. Further data from post-market and health economics studies may lead to future recommendations for use of GASTROClear and gastroscopy in mass screening.
GASTROClear is an in vitro diagnostic test which must be ordered by a medical professional for a patient meeting the criteria for testing.
No. Patients can have their blood drawn 2 hours after a meal. It is recommended that they do not drink alcohol, smoke, or eat pickled food for at least 1 day before blood collection.
GASTROClear can specifically detect and assess the risk of early stage gastric cancer by quantifying miRNAs. Conventional gastric cancer protein markers such as pepsinogen 1 (PG1), pepsinogen 2 (PG2) and gastrin-17 (G-17) specifically detect atrophic gastritis rather than gastric cancer. Although atrophic gastritis sometimes progresses to gastric cancer, many patients with atrophic gastritis will not develop cancer. Tumour markers such as CA72-4, CEA, and CA19-9 are also commonly used to detect various cancers but they also have low sensitivity and are not suitable for detecting early stage gastric cancer. Our published research shows that GASTROClear is around 20% more accurate than any other conventional blood-based biomarker tests for gastric cancer detection:
GASTROClear is the world’s first liquid biopsy (blood) test that has received regulatory approval for in vitro diagnostic use in early detection of gastric cancer. Other cancer liquid biopsy diagnostic tests based on detection of circulating tumour DNA (ctDNA) or circulating tumour cells (CTCs) are predominantly still in the research stage and the studies have so far reported relatively poor sensitivity (below 50%) in detecting early stage gastric cancers. GASTROClear is validated to have high sensitivity (above 80%) in detecting early stage gastric cancer because it measures miRNA biomarkers which are present at relatively high levels in the blood of gastric cancer patients, even when the cancer is in the early stages (stage I and II).
GASTROClear was developed specifically as a miRNA-based diagnostic test for detecting gastric cancer in conjunction with gastroscopy. GASTROClear is the first such test to be launched but similar miRNA-based tests for other cancers are in the pipeline and will be launched once development and clinical validation studies are completed. Eventually, multiple miRNA-based tests can be combined for accurate multi-cancer early detection through one blood draw from a patient.
GASTROClear detects gastric cancer-associated miRNAs are secreted by cancer cells in the stomach. Gastric cancer develops over an extended period of time. As a result, the amount of secreted gastric cancer-associated miRNAs may change over time as the cancer develops. Therefore, the miRNA test can assess gastric cancer risk based on miRNA quantities at that point in time. In contrast, a gastroscopic examination involves having a medical specialist check the stomach mucosa using a gastroscope. A specialist can visually detect the lesion through the gastroscope if it is sufficiently large. However, gastroscopy is a relatively costly and invasive procedure that requires a specialist to perform and patients who should be screened for gastric cancer may refuse to undergo gastroscopy because of these reasons. GASTROClear is not designed to replace gastroscopy but is a complementary detection technique. However, patients who refuse gastroscopy initially may be persuaded to undergo the procedure if they get a “high risk” result from the GASTROClear test.
The test report will include a gastric cancer risk score which will determine if the person tested has low, intermediate, or high gastric cancer risk compared to the general population. Each gastric cancer risk category will come with an interpretation and specific follow-up recommendations for doctors to act on:
Yes. The Code of Practice is a guidance document issued under the PHMC Act to licensees providing clinical genetic/genomic testing and laboratory genetic/genomic testing services. GASTROClear is considered a “genetic test” under the definitions of the Code of Practice because:
- The test quantitates the expression of a specific part of the human gene; and
- miRNA expression levels are recognized to be affected by variants in miRNA genes and hereditary variants may underpin quantitative levels detected
GASTROClear is considered a Level 1 genetic test under the Code of Practice since the test does not pose any additional risks in terms of identification of germline variants.
The GASTROClear test must be ordered by a registered medical practitioner. As Level 1 tests do not pose additional risks as mentioned, the Code of Practice does not impose any additional requirements with regard to consent taking or counselling beyond what would be considered good clinical practice in the ordering of laboratory tests for clinical purposes.
No. A “low risk” test result indicates that the patient’s current risk of having gastric cancer is low compared to the general population. As GASTROClear is not a standalone diagnostic test, the risk score alone does not reflect whether the patient has gastric cancer or not, nor the extent of the disease. Gastroscopy and histopathological examination by specialists are needed for clinical diagnosis of gastric cancer.
No. A “high risk” test result indicates that a patient’s current risk of gastric cancer is high compared to the general population. As GASTROClear is not a standalone diagnostic test, the risk score alone does not reflect whether the patient has gastric cancer or not, nor the extent of the disease. Gastroscopy and histopathological examination by specialists are needed for clinical diagnosis of gastric cancer.
Cancers develop over time and GASTROClear can only indicate a patient’s risk of gastric cancer at the time of the test. Patients need to carry out the GASTROClear test regularly to monitor their risk of gastric cancer, especially if they have elevated risk due to other risk factors like environment and lifestyle. High or medium risk individuals should be screened more regularly than low risk individuals.
GASTROClear has been shown to be a specific test for gastric cancer with little or no cross-reactivity with other cancer types. A small number of blood samples from patients with kidney and colorectal cancer scored as “high risk” when tested with GASTROClear.
GASTROClear is specifically designed to differentiate gastric cancer from gastritis as well as other gastric conditions and pre-malignant lesions. GASTROClear has no cross-reactivity for gastritis.
More longitudinal clinical studies need to be done to study this possibility. In our clinical validation study, 60% of patients with gastric high grade dysplasia (a pre-malignant lesion which is known to have a high risk of progressing to gastric cancer) scored as “high risk” using GASTROClear.
Clinical studies are currently underway by the Singapore Gastric Cancer Consortium to provide clinical evidence for this use of GASTROClear. However, GASTROClear is specifically designed to differentiate gastric cancer from pre-malignant lesions such as IM. In the discovery and verification cohorts, about 50% and 75% of the non-cancer control patients, respectively, had IM. Similarly, the gastric cancer patients used in these cohorts had a mix of patients with and without IM. Therefore, there is preliminary evidence that GASTROClear is able to identify gastric cancer from patients with IM, though this has to be confirmed through the longer-term monitoring study that is underway.