Gastric cancer is one of the most common malignant tumors in the world, and China is a high incidence area of gastric cancer, and its mortality rate ranks the second in malignant tumors. Since early gastric cancer has no specific symptoms and signs, the consultation rate of patients is low, and the proportion of gastroscopy screening in China is not high, so the detection rate of early gastric cancer is low, and 84% of patients are already in the progressive stage when detected. In Japan, early gastric cancer accounts for more than 80% of the total number of detected gastric cancer, and in Korea, it is 46%-67%. The prognosis of gastric cancer is directly related to its stage. The 5-year survival rate after surgery for early-stage gastric cancer is >95%, while that for progressive stage is 20%-30%. Early diagnosis and early treatment are important to improve the therapeutic efficacy and reduce the death rate of gastric cancer.
I. Serological tests
1.Tumor markers.
Tumor markers are substances synthesized or released by tumor cells or produced by host cells in response to tumor during the process of tumorigenesis and proliferation, and exist in cells, tissues or body fluids. Currently, the commonly used ones are carcinoembryonic antigen, CA19-9, CA72-4, CA125, CA242, etc. A recent meta-analysis in Japan showed that the positive rates of CA72-4, CA19-9 and CEA were relatively high in gastric cancer, with overall positive rates of 29,9%, 27,0% and 24,0%, respectively. The positive rates of CA724 in stage I-IV gastric cancer were 12,0%, 15,6%, 36,7% and 49,6%, respectively, while the positive rates of CA72-4, CA19-9 and CEA in stage IV gastric cancer were less than 50,0% and only about 10% in early gastric cancer.
In addition, serum gastric cancer-associated antigens were discovered by Academician Fan Daiming’s team, which also established a highly sensitive immuno-PCR technique for detecting serum MG7-Ag. The results showed that the sensitivity of this method was 77.5%, specificity was 95.6%, and accuracy was 73.1%, among which 55.0% were stage I and II gastric cancer. widely used.
2.Pepsinogen.
Two isoenzymes PGⅠ and PGⅡ are expressed in human body, PGⅠ is produced by gastric bottom glands, while all gastric mucosa can secrete PGⅡ, 90% of which are secreted into gastric lumen and 1% into blood. Low serum PGI value can reflect the degree of progression of atrophic gastritis. according to Miki, PGⅠ≤70ng/ml and PGⅠ/PGⅡ≤3,0 defined as positive, the sensitivity of predicting atrophic gastritis is 93,0%, specificity 88,0%, and the sensitivity of detecting gastric cancer is 84,6%, specificity 67,2%. In Japan, serum PG measurement has been used for population screening since the 1990s, and the detection rate of gastric cancer is 0.28% with combined PG test and imaging screening, which is higher than 0.10% with imaging screening alone, and 88.0% is early gastric cancer. However, PG detection is affected by gender, age, tumor tissue type, lesion site and infiltration depth, and the sensitivity and specificity of gastric cancer detection vary in different countries and regions, so large sample studies are needed to set reference standards for each region and improve the effectiveness of PG detection. However, serum PG test for primary screening of gastric cancer has the advantages of high sensitivity, easy acceptance and low cost, which is suitable for large population screening and is important for improving the early diagnosis rate of gastric cancer.
3.H. pylori antibody.
Hp is a Gram-negative bacillus parasitic in gastric mucosa, which is an independent pathogenic factor of non-cardia gastric adenocarcinoma. its carcinogenic effect depends on the virulence factors of Hp, mainly cytotoxin-associated protein A (CagA) and vacuolar toxin A (VacA). Hp infection causes gastric mucosa to experience inflammation, atrophy, intestinal epithelial chemosis, heterogeneous hyperplasia, and then evolve into cancer. Combined detection of serum Hp antibodies and PG is divided into 3 groups according to the results, group A [Hp(-), PG(-)], group B [HP(+), PG(-)], and group C [Hp(+), PG(+) and Hp(-), PG(+)], called the ABC method. A 14-year-long study of 8286 healthy people in Japan showed that the incidence of gastric cancer in the above three groups was 0, 0, 21% and 1, 87%, respectively. This method can screen not only the high-risk group of gastric cancer, but also the low-risk group of gastric cancer, and is useful for the preliminary screening of gastric cancer related brother plaque plastic
4.Succrose permeability measurement.
Based on the principle that sucrose does not permeate the gastric mucosa without lesions and is rapidly decomposed in the small intestine, but permeates in the diseased gastric mucosa and is absorbed into the blood, the permeability of gastric mucosa can be understood by measuring the concentration of sucrose in blood. was 92,3% and the specificity was 93,8%. This method is simple, can be automated, and is suitable for mass screening of gastric cancer, but the sample size of the above study is small, and there are few relevant studies, so the value of early gastric cancer screening has yet to be confirmed by large-scale clinical studies.
Urine free amino acid test
Human amino acids are divided into endogenous and exogenous, which together form the body’s amino acid metabolic pool and participate in systemic metabolism. Endogenous amino acids are involved in the physiological regulation of the body, such as gene expression, cell proliferation, and inflammatory response. Malignant cells are characterized by rapid division and high metabolism, requiring large amounts of amino acids for protein and nucleic acid synthesis, resulting in altered amino acid metabolic pools. Specific amino acid metabolism is associated with specific organs, and some amino acids are associated with specific cancers. A study on urinary amino acid profile and gastric cancer showed that urinary free amino acids were elevated in valine, leucine, and isoleucine, decreased in histidine and methionine, and significantly lower in aspartate in gastric cancer patients compared to normal adults. In addition, the urinary amino acid profiles of patients with early-stage gastric cancer differed from those of patients with progressive gastric cancer, with isoleucine and valine levels decreasing in progressive gastric cancer compared with early-stage gastric cancer. There are few studies on the relationship between urinary amino acids and gastric cancer, but metabolomics as a branch of systems biology has developed rapidly in recent years and has good prospects in the future.
III. Intrinsic fluorescence spectroscopy of gastric juice detection
The changes of various components of gastric juice can directly reflect the changes of gastric internal environment due to gastric lesions, and the intrinsic fluorescence spectra of gastric juice in normal and malignant tumor tissues are very different. Studies have shown that the first wave of intrinsic fluorescence at 288 nm is significantly higher in gastric cancer patients than in those with benign gastric lesions. In the ROC curve, P1FⅠ≥76,5 was taken as the best threshold, and its sensitivity of diagnosing gastric cancer was 83,2%, specificity was 80,7%, and accuracy was 82,0%. The sensitivity and specificity of this method are high, but the sensitivity and specificity for early gastric cancer have not been reported. In addition, a simple, economical and painless method to obtain gastric juice needs to be found before it can be promoted.
Imaging examination
X-ray – gas-barium double imaging is a traditional examination method, which can clearly show the fine structure of gastric mucosa through double contrast images, mucosal images, filling images and compression images. The sensitivity of this method is 60%-80% and the specificity is 80%-90%, and it is used for the general screening of gastric cancer in Japan since the early 1960s. In Japan, the detection rate of early gastric cancer can be more than 80% by using gas-barium imaging combined with gastroscopy to screen the population. However, it has been gradually replaced by gastroscopy due to the low diagnosis rate of early gastric cancer because it has not received much attention and is greatly influenced by the operator’s experience.
V. Endoscopy
Gastroscopy can not only directly observe gastric mucosal lesions, but also obtain lesion tissues for pathological examination, which is currently the main method for gastric cancer diagnosis. The sensitivity of gastroscopy in screening gastric cancer ranges from 60% to 84%. Compared with X-ray-air-barium double imaging, gastroscopy has higher detection rate of gastric cancer and the ability to detect early cancer. However, the literature reports that the differences between gastroscopy and gas-barium imaging, calculated by the incidence method, were not statistically significant in both prevalence screening 88,6% and 83,1%, and in incidence screening 95,4% and 85,5%, although the sensitivity of gastroscopy was higher than that of gas-barium imaging. This method avoids the excessive diagnostic bias and length bias of previous methods of studying detection rates, and can more accurately evaluate the value of gastroscopy and dual X-ray-gas-barium imaging in gastric cancer screening. Gastroscopy is important for early gastric cancer screening, but currently it is difficult to be applied to large scale population due to the problems of cost, safety, compliance, technical training and operator’s lack of awareness of early gastric cancer.
At present, there is no comprehensive screening strategy for gastric cancer in China. Based on the above screening methods, the author believes that screening can be performed according to the incidence of gastric cancer in different regions. In conclusion, as China is a high incidence area of gastric cancer, only by establishing a set of screening programs suitable for our population and regularly screening asymptomatic and natural people can we improve the detection rate of early gastric cancer and reduce the death rate.