Gastrointestinal stromal tumors (GISTs) can occur anywhere in the digestive tract but are most common in the stomach (60–70%) and small intestine (25–30%)[2, 12]. Local GISTs are mainly treated by surgery. Adjuvant treatment is not required for low-risk and intermediate-risk GISTs or high-risk GISTs that are sensitive to imatinib [13]. Approximately 30% of GISTs are malignant, and their complex biological behavior is related to the malignant transformation of the tumor, so the prognosis of patients cannot be determined by only a few factors[14]. A retrospective study did not observe the effect of gender on the prognosis of GISTs [9]. However, in this study, we found that gender is an independent predictor of gastric GIST prognosis, and male patients have a higher risk of death than female patients. To the best of our knowledge, this is the first study to study the relationship between gender and gastric GIST prognosis through PSM, and the sample size was relatively large.
This study collected data from the SEER database of 1,050 gastric GIST patients. We found that the incidence of GISTs was related to marital status, surgical treatment, tumor size, and mitotic index, which was consistent with the findings of a previous study[15]. Some previous studies have found that GISTs are more common in men and that its incidence in black individuals is approximately twice that in white individuals [16, 17]. However, in this study, we found that female patients had a higher incidence of gastric GIST than males (51.2% vs 48.8%), and white individuals had a higher incidence than black individuals (62.0% vs 24.8%), which is inconsistent with previous research results. At present, the prognostic assessment of GISTs is mainly based on the NIH consensus, which is based on tumor size, mitosis number, and tumor location but does not include age, gender, ethnicity, surgical treatment, or other factors[5]. Zhang et al. found that gender, tumor location, size, mitotic number, and rupture were associated with recurrence of GISTs[18]. In this study, male patients and female patients showed significant differences in marital status, surgical treatment, tumor size, and mitotic index, so we performed propensity score matching to avoid these confounding factors affecting the credibility of our results.
After property score matching, all baseline variables between male patients and female patients were completely balanced, and we found that male patients had a higher risk of death than female patients. The result of our study is consistent with that of a previous study [8]. The correlation between gender differences and prognosis may be due to sex hormones. Sex hormone levels vary widely between men and women. Studies have found that sex hormones and their metabolites are involved in the development of many tumors, such as colorectal cancer, prostate cancer, breast cancer and lung cancer[19–22]. The sex hormone signaling pathway may affect cancer susceptibility and the tumor microenvironment through a variety of mechanisms. For example, fat-soluble steroid hormones act on intracellular receptors, causing their receptors to shuttle through the nucleus, affecting DNA methylation and chromatin conformation[23]. Sex hormones also regulate angiogenesis and inflammation, affecting cancer progression between the sexes. ERβ levels are usually reduced in cancer, and continuous ERβ expression is a marker of good tumor prognosis. In many cases, higher estrogen signaling activates ER, providing a protective effect from tumors[24]. Studies have found that estrogen plays a key role in maintaining gastrointestinal epithelial barrier function, and estrogen may reduce the risk of gastrointestinal tumors[25, 26]. In addition, a retrospective study found that GIST estrogen receptor expression was negative, but the expression of progesterone (5.4%) and androgen receptor (17.6%) was observed in some GISTs[27].
We used a Cox model to predict risk factors affecting OS in patients with gastric GIST, and we found that gender is an independent prognostic factor for gastric GIST patients. A previous study revealed that gender was associated with GI bleeding, and male GIST patients were more likely to have GI bleeding. In addition, GI bleeding is a risk factor for poor prognosis in GIST patients, men with GIST are more likely to have GI bleeding, and women have higher OS and CSS rates[15, 28]. Currently, surgical resection is the main treatment for GISTs[3]. Even if the patient has undergone radical surgery, the recurrence rate is still 40–80%[29]. Patients with uncontrollable gastrointestinal bleeding often require emergency surgery[30]. In addition to surgical treatment, treatment with imatinib mesylate, a small molecule tyrosine kinase inhibitor, significantly improved the prognosis of GIST [31]. GIST survival rates were higher in women than in men during imatinib treatment[32]. Similarly, in a confirmed case study of c-KIT, women had higher 5-year survival rates than men (75–52%)[33].
Our research has some limitations. First, the data we collected from the SEER database are from American patients, so the results of the study cannot be generalized to other populations. Second, this was a retrospective study, and the SEER database lacks some treatment data, including information on targeted drug therapies such as imatinib, which is also important for survival analysis. Therefore, large, randomized, controlled studies are still needed.
Perspectives and significance
In summary, based on the SEER database, we investigated for the first time the effect of gender on the survival of gastric GIST patients. We found that male gastric GIST patients have worse survival rates than female patients. Further research is still needed to clarify the specific mechanism of gender and gastric GIST prognosis. In addition, marital status and tumor grade are also independent risk factors that affect the prognosis of gastric GIST patients. In general, male gastric GIST patients are at greater risk, so the sooner male patients receive treatment, the better their prognosis will be.