GC were responsible for the majority of cancer-related deaths globally before[14]. Stomach cancer posed a significant burden primarily in East Asia while Western Europe and North America experienced comparatively lower incidence rates[15, 16]. It is projected that between 2021–2035 there will be approximately 10 million newly diagnosed cases of gastric cancer resulting in around 5.6 million fatalities; however, a considerable percentage ranging from 7.6–35.% could potentially be prevented through diverse preventive measures[17]. This research specifically targeted patients suffering from an upset stomach who exhibited GIM (an intermediate precancerous gastric lesion)[18]. Many individuals seeking outpatient care reported experiencing symptoms related to their stomach but refrained from using prescribed medications instead opting for self-administration of drugs like omeprazole; consequently excluding them from participation in this study due to these preferences.The prevalence rate of Hp infection observed during this investigation stood[19]. This may be attributed to the fact that our hospital received a significant influx of patients referred for upper gastrointestinal tract assessment and treatment due to unsuccessful eradication of Hp, leading to a higher incidence of Hp infection compared to previous findings. Similarly, a study conducted in Thailand also reported elevated rates of Hp infection in cases of GIM[4].
Previous studies have identified risk factors linked to the development of GIM. Both bacterial virulence and host immune response play a role in gastric mucosal inflammation. Gender is a demographic variable that influences the occurrence of GIM. This study found a significant association between male patients and the presence of GIM in their gastric pathology. This aligns with previous research indicating a higher prevalence of GIM among males, possibly due to prolonged gastric inflammation. Additionally, PGⅡ as a comorbidity was independently associated with the development of GIM, although no prior reports have explored this relationship. The mechanism behind this association remains unclear. Lastly, the most crucial risk factor for developing GIM was having a history of Hp eradication since addressing this modifiable factor can halt gastric inflammatory processes and subsequent cancer cell differentiation.
This study includes 3 clinical implications. Firstly, there is a significant association between low levels of PGⅡ and the prevalence of GIM. Previous research has already established a strong link between the presence of GIM and symptoms of dyspepsia[20]. PGⅡ levels serve as an indicator for the overall secretion function of the gastric mucosa, with lower levels suggesting reduced secretion function. Following the development of GIM, chief cells that secrete pepsin undergo acute reprogramming into mucin-secreting cells involved in wound healing[21]. Consequently, there is a decrease in the number of acid-producing cells within the gastric mucosa in individuals with GIM. Therefore, low levels of PGⅡ may indicate an increased risk for outpatients developing GIM. Hence, when utilizing serum gastric function as part of gastric cancer screening protocols, it is important to consider the role played by PGⅡ within the evaluation system. Some studies have indicated that individuals with PGI levels above 127.20 ng/mL are more likely to exhibit signs of GIM compared to those with high PGⅡ levels[22]. This discrepancy could be attributed to factors such as outpatient patients being included in this study where even individuals from the NC group displayed some level of stomach inflammation; thus patients within the GIM group might present low PGⅡ levels.
Secondly, it is worth noting that gender was identified as an independent factor influencing the prevalence of GIM. However, it should be emphasized that the incidence of GIM can vary among individuals of the same gender but with different levels of PGⅡ. It is widely acknowledged that males have a strong association with the development of GIM [23, 24]. Our study also observed a higher susceptibility to GIM in males. Furthermore, females with lower levels of PGⅡ are more prone to developing GIM. This implies that PGⅡ may play a significant role in the occurrence of GIM across both genders.
Thirdly, although the eradication of Hp has been closely linked to the prevalence of GIM[25, 26], there was no observed association between Hp eradication history and the occurrence of GIM in individuals with high PGⅡ levels. Conversely, individuals with low PGⅡ levels who had undergone Hp eradication exhibited a higher incidence of GIM compared to those with high PGⅡ levels and no prior history of Hp eradication. This indicates that the levels of PGⅡ play a significant role in the development of GIM among individuals who have undergone Hp eradication treatment.
Consistent with the gender and eradication history of Hp, the incidence of GIM was higher in females with a history of Hp eradication who had low levels of PGⅡ compared to those with high levels. This suggests that PGⅡ levels may play a significant role in the development of GIM in females with a history of Hp eradication.
In the high PGⅡ group, males with and without a history of Hp eradication exhibited a higher occurrence of GIM compared to females without a history of Hp eradication. Conversely, in the low PGⅡ group, both males and females who had undergone Hp eradication displayed an increased incidence of GIM when compared to females without a history of Hp eradication. These findings suggest that the incidence of GIM is influenced by sex and history of Hp eradication differently depending on the level of PGⅡ.
The strength of our study lies in its extensive population-based analysis, which identified predictors for GIM. Moreover, it indicated that low PGⅡ contributed to GIM. Additionally, it highlighted the association between low PGⅡ levels and GIM development. However, this retrospective cross-sectional investigation encountered certain limitations. Firstly, incomplete data in some patients prevented us from conducting severity grading of GIM using the OLGIM system. Secondly, as this study was conducted at a single center, its robustness may be slightly diminished compared to multi-center studies. Nonetheless, our findings provide compelling evidence suggesting that low PGⅡ levels could potentially serve as an indicator for increased risk of gastric mucosal intestinal metaplasia among outpatients.
In conclusion, males with low PGⅡ levels and a history of Hp eradication could be significant predictors for GIM in outpatients experiencing stomach discomfort. Low PGII levels may indicate an increased risk of GIM; however, it is also important to consider the patient's gender and history of Hp eradication.