Analysis of the Results of Gastrin-17 and its Related Inuencing Factors in Health Check-Up Population

Background: To analyze the difference of serum gastrin-17 levels in different sexs, ages, and body mass index (BMI) of healthy people, and to explore the correlation between gastrin 17 and pepsinogen, in addition to study the inuence of Helicobacter pylori infection and various inammatory factors on the secretion level of gastrin-17. Methods: 531 subjects who received physical examination in our center from April 2019 to December 2019 were enrolled in the study. All the staff were tested for gastrin 17 (G17), pepsinogen I (PGI), pepsinogen II (PGII), PGI / PGII (PGR), Helicobacter pylori (Hp) and C-reactive protein (CRP) and other inammatory factors. To compare the difference of G17 secretion in different populations and its correlation with PG, then to understand the HP infection and the inuence of inammatory indicators on G17. Results: There was no signicant difference in the secretion level of G17 in different sex, age and BMI (P > 0.05); G17 was positively correlated with PGI and PGII, but negatively correlated with PGR; the level of G17 in Helicobacter pylori positive patients was 10.16±12.84, which was signicantly higher than that in negative patients(3.27±6.65), P =0.017, 95% CI: 1.713 (1.100, 2.668); the increase of serum amyloid A(SAA) in different inammatory indicators was the high-risk factor of G17 abnormality, P=0.016, 95% CI: 2.692 (1.202, 6.028), obviously CRP and erythrocyte sedimentation rate (ESR) had no effect on G17 abnormalities. Conclusions: The secretion of G17 is closely related to PG and HP. Combined screening is helpful for early screening of gastrointestinal diseases in high-risk of gastric cancer, but the inuence of inammatory

Conclusions: The secretion of G17 is closely related to PG and HP. Combined screening is helpful for early screening of gastrointestinal diseases in healthy or high-risk groups of gastric cancer, but the in uence of in ammatory indicators on G17 should be excluded to improve the reliability of the results.

Background
Gastric cancer is a common digestive tract malignant tumor. Its incidence rate and mortality rate rank the forefront of global malignant tumors [1] . It is the nal result of the progression of precancerous lesions, including non-atrophic gastritis, atrophic gastritis, intestinal metaplasia and dysplasia. Epidemiological studies show that the 5-year survival rate of early gastric cancer is as high as 90%, while that of advanced gastric cancer was only 25% [2] . Therefore, early screening, early diagnosis and early treatment are important measures to reduce the mortality of gastric cancer.
Compared with the markers in tissues, serological markers are less invasive, easier to obtain, lower cost and shorter time-consuming. Currently available serological markers associated with gastric diseases include Pepsinogen I(PGI), Pepsinogen II(PGII), PG I/PG II(PGR), Gastrin 17(G17) and anti-Helicobacter pyliri (HpIgG). Based on the existing evidence, these serological markers may help to identify those with precancerous lesions who should be referred to gastroscopy [3] . Although the use of these biomarkers of the stomach for serological biopsy of gastric mucosa has been used for the detection of gastric cancer and precancerous lesions for more than 20 years, previous studies mainly focused on PGI, PGI / II ratio and HpIgG, while other biomarkers such as G-17 and PGII were ignored [4] .
G17 is closely related to in ammation, immunity, invasion and metastasis of gastric cancer cells. It has a low level of expression in healthy people. When the pathological changes of gastritis, gastric cancer and others occur, the level of the expression increases signi cantly [5] . The increase or decrease of G17 can prompt the occurrence risk of gastric cancer. The increase or decrease of G17 can prompt the occurrence risk of gastric cancer. It is not a direct cause of gastric cancer in itself, but it can promote some carcinogenic factors, activate multiple signal transduction pathways, produce anti apoptotic and antiin ammatory effects, and induce gastric acid secretion, thus leading to tumorigenesis [3,6] . The aim of this study was to analyze the G17 ndings and possible in uencing factors of normal physical health people, in order to understand the secretory characteristics and application value of G17 in healthy people. Methods 1. Participants: a total of 531 healthy subjects who received physical examination in the healthcare department center of Wuhan Union Hospital from April 2019 to December 2019 were selected for the study, including 307 males and 224 females, aged 22-78 years. In addition to routine physical examination, G17, PGI, PGII, PGR, Hp typing, C-reactive protein(CRP), erythrocyte sedimentation rate(ESR) and serum amyloid A(SAA) were detected. Excluding acute and chronic in ammatory disease, liver and gallbladder disease, diabetes, blood disease, kidney disease, rheumatic immune disease, tumor, etc.
Grouped according to age, BMI and Hp typing.

Methods
2.1 Serological test: About 3ml fasting venous blood was collected, after centrifugation, serum was obtained. The serum PGI, PGII, PGR and G17 were quantitatively detected by enzyme-linked immunosorbent assay (ELISA). The testing equipment is BIOHIT Healthcare(Hefei) Co., Ltd and Wuhan Yolins Technology Trade Co., Ltd. According to the requirements of the kit, PGI < 70ng / ml concurrently with PGR < 3 were de ned as PG positive, and G17 < 1 or > 15pmol / l was regarded as G17 positive.

13 C breath test:
The test was carried out on an empty stomach in the early morning. The equipment used in the research is the kit produced by Shenzhen Zhonghe Headway Bio-Sci Tech Co., Ltd, along with the HCBT-02 13 C breath test instrument. The positive standard of Hp infection was 4.0 times higher than the reference value.
2.3 In ammatory index detection: CRP was measured by immuno uorescence quantitative detection. The apparatus used was I-CHROMA Rester immuno uorescence analyzer provided by Boditech Med Inc; ESR was calculated by Westergren method; SAA adopts SIEMENS BN prospect speci c protein analyzer as well as matching reagents, strictly according to the operation manual.
2.4 Statistical methods: Spss19.0 statistical software was used for analysis. T test was used in the comparison between the two groups, while the One-way ANOVA was used for multiple groups. Correlation analysis was performed by Spearman rank correlation test, with calibration level of 0.01. The single factor Logistic regression analysis was used to analyze the in uencing factors. P < 0.05 was statistically signi cant. Results 1. The difference of gastrin 17 secretion in different sex, age, and BMI There was no signi cant difference in the secretion level of G17 between male and female, the same as different age groups and BMI groups (P > 0.05) ( Table 1). 2. Correlation analysis between G17 and PG G17 and PG were signi cantly correlated, P = 0.000, G17 was positively correlated with PGI and PGII (r = 0.322 and 0.452), but negatively correlated with PGR (r = − 0.367) ( Table 2).

Secretion of G17 in Hp infected population
The secretion of G17 in HP infected population (10.16 ± 12.84) was signi cantly higher than that in uninfected (3.27 ± 6.65) ( Table 3).

Analysis of in uencing factors of G17
The risk factors of G17 secretion abnormality were analyzed, including sex, age, HP infection, CRP, SAA, ESR. It was found that the risk of abnormal G17 secretion in Hp infected patients was 1.713 times higher than that in uninfected patients, which was 2.692 times in patients with increased SAA. Other factors had no effect on the excretion of G17 (Table 4).

Discussion
Gastrin is a gastrointestinal hormone secreted by gastric antrum G cells, and its level is mainly affected by the number and function of G cells, as well as by the negative feedback regulation of gastric acid [7] . As a gastrointestinal hormone, G17 can not only maintain the integrity of digestive tract structure, but also regulate the function of digestive tract. Gastrin 17 level can be used as a biomarker to re ect the function and structure of gastric mucosa. Combined with serum PG and G17 levels, it can provide diagnostic information of gastric mucosa, re ect the degree of gastric aging too, and distinguish pathological state from healthy state [8] . G17 also has multiple biological functions of promoting proliferation and inhibiting apoptosis. The changes of serum G17 level can re ect the state of gastric mucosal lesions, so it can be used as a screening index for gastric cancer and precancerous diseases.
PG is the precursor of pepsin, which is mainly secreted by the main cells. PGI, PGII and their ratio are considered as predictors of various gastric diseases, including atrophic gastritis (AG) and intestinal metaplasia (IM), which are de ned as precancerous lesions of gastric cancer [9] . One meta-analysis showed that the sensitivity and speci city of PG in the diagnosis of AG were 69% and 88% [10] , while another meta-analysis for joint detection showed that the sensitivity and speci city were 74.7% and 95.6% [11] , which were also higher than that of G17 alone in the diagnosis of AG [12] . In this study, G17 and PG showed a weak to moderate correlation, consistent with Wang Rui`s result [13] , which side con rmed that the combined screening effect of G17 and PG was better.
HP positive is considered as a primary carcinogen. HP infection can induce cell division, increase the probability of cell gene mutation, and play an important role in the occurrence and development of gastric cancer [14] . Studies on Helicobacter pylori infection were carried out in China and South Korea respectively. It was found that in Hp positive patients the serum levels of G-17, PGI and PG II increased, especially PG , while the ratio of PGI/PGII decreased [8,15] . This study also found that the level of G17 in Hp positive group was signi cantly higher than that in negative group, which was showing no difference with other studies [16,17] . Patients with Helicobacter pylori infection and low PGI / PGII ratio should be considered as higher risk of GC and secondary diagnosis (endoscopy and histology) should be performed [18] .
Because G17 is easily affected by many factors, such as lesion location, atrophic degree, HP infection, and even in ammatory indicators, for example, this study found that the risk of abnormal G17 in patients with elevated serum amyloid A increased by 2.692 times, so it is not a major diagnostic indicator, but can be combined with PG and Hp detection as a reference to further improve the diagnosis rate of atrophic gastritis and early gastric cancer, also can directly screen high-risk groups. Arrange endoscopy and histological examination according to the results, enhance the compliance of screening and treatment of gastric diseases, avoid unnecessary radiation and discomfort caused by endoscopic examination.
In recent years, Chinese scholars have been drawing on the overseas screening mode of gastric cancer, combined with the situation of China and the current epidemiological investigation, have successively promoted the "four items gastric function" test combined with gastrin-17, pepsinogen, and Helicobacter pylori. With expectation to nd and optimize the screening path of early gastric cancer suitable for China's national conditions, timely provide evaluation and intervention suggestions for high-risk groups, early screening, early diagnosis, early treatment, reduce mortality, prolong life, and protect people's health.

Conclusions
The incidence rate and mortality of gastric cancer in China are higher. Precancerous lesions are the key stage of the development of gastric cancer. Therefore, it is necessary to actively nd effective means to screen gastrointestinal diseases. Combined screening is helpful to early screen gastrointestinal diseases in healthy people or high-risk groups of gastric cancer, but the in uence of relevant factors should be excluded to improve the reliability of the results.

Declarations
Ethics approval and consent to participate The institutional review board of Shanghai Changhai Hospital Ethics Committee approved all procedures.
Consent to Participate All participants were informed about their con dentiality and were asked to voluntarily electronically consent to participate. There was no incentive for participation. "Your involvement in the study is voluntary, and you may choose not to participate or to stop at any time without penalty or loss of bene ts to which you are otherwise entitled."

Consent for publication
Not applicable.

Competing interests
The authors declare that they have no competing interests.

Funding
There is no funding to report.