Background/Objectives: Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, with significant racial and ethnic disparities in incidence, molecular characteristics, and patient outcomes. However, genomic studies focusing on Hispanic/Latino (H/L) populations remain scarce, limiting our understanding of ethnicity-specific molecular alterations. This study aims to characterize pathway-specific mutations in TP53, WNT, PI3K, TGF-Beta, and RTK/RAS signaling pathways in GC and compare mutation frequencies between H/L and Non-Hispanic White (NHW) patients. Additionally, we evaluate the impact of these alterations on overall survival using publicly available datasets. Methods: We conducted a bioinformatics analysis using publicly available GC datasets to assess mutation frequencies in TP53, WNT, PI3K, TGF-Beta, and RTK/RAS pathway genes. A total of 800 patients were included in the analysis, comprising 83 H/L patients and 717 NHW patients. Patients were stratified by ethnicity (H/L vs. NHW) to evaluate differences in mutation prevalence. Chi-squared tests were performed to compare mutation rates between groups and Kaplan–Meier survival analysis was used to assess overall survival differences based on pathway alterations among both H/L and NHW patients. Results: Significant differences were observed in the TP53 pathway and related genes when comparing GC in H/L patients to NHW patients. TP53 mutations were less prevalent in H/L patients (9.6% vs. 19%,p= 0.03). Borderline significant differences were noted in the WNT pathway when comparing GC in H/L patients to NHW GC patients, with WNT alterations more frequent in H/L GC (8.4% vs. 4%,p= 0.08) and APC mutations being significantly higher (3.6% vs. 0.8%,p= 0.05). Although alterations in PI3K, TGF-Beta, and RTK/RAS pathways were not statistically significant, borderline significance was observed in genes related to these pathways, including EGFR (p= 0.07), FGFR1 (p= 0.05), FGFR2 (p= 0.05), and PTPN11 (p= 0.05) in the PI3K pathway and SMAD4 (p= 0.08) in the TGF-Beta pathway. Survival analysis revealed no significant differences among H/L patients. However, NHW patients with TP53 and PI3K pathway alterations exhibited significant differences in overall survival, while those without TGF-Beta pathway alterations also showed a significant survival impact. In contrast, WNT pathway alterations were not associated with significant survival differences. These findings suggest that TP53, PI3K, and TGF-Beta pathway disruptions may have distinct prognostic implications in NHW GC patients. Conclusions: This study provides one of the first ethnicity-focused analyses of TP53, WNT, PI3K, TGF-Beta, and RTK/RAS pathway alterations in GC, revealing significant racial/ethnic differences in pathway dysregulation. The findings suggest that TP53 and WNT alterations may play a critical role in GC among H/L patients, while PI3K and TGF-Beta alterations may have greater prognostic significance in NHW patients. These insights emphasize the need for precision medicine approaches that account for genetic heterogeneity and ethnicity-specific pathway alterations to improve cancer care and outcomes for underrepresented populations.
**背景/目的：** 胃癌是全球癌症相关死亡的主要原因之一，其发病率、分子特征及患者预后存在显著的种族和民族差异。然而，针对西班牙裔/拉丁裔人群的基因组研究仍然匮乏，限制了我们对其种族特异性分子改变的理解。本研究旨在分析胃癌中TP53、WNT、PI3K、TGF-β及RTK/RAS信号通路的特异性突变，并比较西班牙裔/拉丁裔患者与非西班牙裔白人患者之间的突变频率。此外，我们利用公开数据集评估了这些改变对总生存期的影响。 **方法：** 我们利用公开的胃癌数据集进行了生物信息学分析，以评估TP53、WNT、PI3K、TGF-β及RTK/RAS通路相关基因的突变频率。分析共纳入800例患者，包括83例西班牙裔/拉丁裔患者和717例非西班牙裔白人患者。按种族/民族分层，以评估突变流行率的差异。采用卡方检验比较组间突变率，并使用Kaplan-Meier生存分析评估基于通路改变的西班牙裔/拉丁裔与非西班牙裔白人患者的总生存期差异。 **结果：** 比较西班牙裔/拉丁裔与非西班牙裔白人胃癌患者时，在TP53通路及相关基因中观察到显著差异。TP53突变在西班牙裔/拉丁裔患者中发生率较低（9.6% vs. 19%，p=0.03）。比较两组胃癌时，WNT通路改变显示出临界显著性差异，在西班牙裔/拉丁裔胃癌中更常见（8.4% vs. 4%，p=0.08），且APC突变显著更高（3.6% vs. 0.8%，p=0.05）。尽管PI3K、TGF-β和RTK/RAS通路的改变无统计学显著性，但在这些通路的相关基因中观察到临界显著性，包括PI3K通路中的EGFR（p=0.07）、FGFR1（p=0.05）、FGFR2（p=0.05）和PTPN11（p=0.05），以及TGF-β通路中的SMAD4（p=0.08）。生存分析显示西班牙裔/拉丁裔患者中无显著差异。然而，存在TP53和PI3K通路改变的非西班牙裔白人患者总生存期有显著差异，而无TGF-β通路改变的患者也显示出显著的生存影响。相比之下，WNT通路改变与显著的生存差异无关。这些发现提示，TP53、PI3K和TGF-β通路失调可能在非西班牙裔白人胃癌患者中具有不同的预后意义。 **结论：** 本研究首次针对胃癌中TP53、WNT、PI3K、TGF-β及RTK/RAS通路改变进行了以种族/民族为重点的分析，揭示了通路失调方面存在显著的种族/民族差异。研究结果表明，TP53和WNT改变可能在西班牙裔/拉丁裔胃癌患者中起关键作用，而PI3K和TGF-β改变可能在非西班牙裔白人患者中具有更重要的预后意义。这些见解强调了需要采用精准医疗方法，考虑遗传异质性和种族特异性通路改变，以改善代表性不足人群的癌症治疗和预后。
肿瘤(癌症)患者之家