PO.MCB09.06 · 分子与细胞生物学
波多黎各粪便样本中鉴定的癌前息肉的性别特异性代谢特征：一项试点研究
Sex-specific metabolic features in pre-cancerous polyps identified in Puerto Rican stool samples: A pilot study
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：在波多黎各，将男性和女性合并计算时，结直肠癌（CRC）是导致癌症死亡的首要原因，且其表现存在显著的性别差异。男性CRC发病率较高，总体死亡率也较高，而女性更常被诊断为对常规治疗反应较差的近端肿瘤。这一模式提示存在影响CRC发生的潜在性别特异性通路。代谢物丰度分析为识别与疾病机制和进展相关的生化改变提供了一种全面的方法。本研究旨在表征癌前息肉与健康样本之间粪便代谢物的差异，并探索一个西班牙裔队列中的性别特异性代谢差异。
方法：采用病例对照设计，分析了97名波多黎各参与者（68名女性，29名男性）的粪便样本，包括有和无结直肠腺瘤者。使用气相色谱-质谱进行代谢物鉴定；随后对光谱峰数据进行归一化，并使用MetaboAnalyst 6.0和RStudio进行分析。采用配对t检验进行两两比较，采用双因素方差分析进行多变量分析以评估显著性。
结果：在各样本中共检测到59种代谢物，在女性中观察到息肉与对照之间存在显著丰度差异：β-丙氨酸（校正p=0.0014）和N-乙酰-L-天冬氨酸（校正p=0.0017）。在男性中我们观察到不同的主要代谢物：白蜡酸（名义p=0.019）和胆固醇（名义p=0.035）。在校正性别后的多变量分析中，在息肉与对照之间鉴定出七种代谢物（名义p<0.05）：烟酸、β-丙氨酸、3,4-二羟基氢化肉桂酸、异亮氨酸、洒李醇酸、棕榈油酸和白蜡酸。
结论：在男性与女性中观察到的不同代谢物谱提供了证据，支持按性别不同的致癌机制，这可能有助于解释所报道的CRC表现和结局的差异。所检测到的代谢物可能是潜在的生物标志物候选，我们将利用更多样本、甚至进行组间匹配来考察微生物组整合分析。这些努力将共同使我们能够更精确地界定性别依赖性代谢通路，最终为量身定制的CRC风险分层和预防策略提供依据。
查看英文原文 English abstract
Background: Colorectal cancer (CRC) is the leading cause of cancer deaths in Puerto Rico when combining men and women, with notable differences in presentation according to sex. Men have a higher incidence of CRC, with a higher overall mortality, while women are more often diagnosed with proximal tumors that respond less effectively to conventional therapies. This pattern suggests the existence of underlying sex-specific pathways that influence CRC development. Metabolite abundance analysis offers a comprehensive approach to identifying biochemical alterations associated with disease mechanisms and progression. This study aimed to characterize metabolite differences in stool between pre-cancerous polyps and healthy samples, and to explore sex-specific metabolic differences in a Hispanic cohort.
Methods: A case-control design was used to analyze stool samples from ninety-seven Puerto Rican participants (68 females, 29 males) with and without colorectal adenomas. Gas chromatography-mass spectrometry was used for metabolite identification; afterwards spectral peak data was normalized and analyzed using MetaboAnalyst 6.0 and RStudio. Significance was assessed using paired t-test for pairwise comparisons and 2-way ANOVA for multivariate analysis.
Results: Fifty-nine metabolites were detected across samples, with significant abundance differences between polyps and controls observed in females: beta-alanine (adjusted p=0.0014) and N-acetyl-L-aspartic acid (adjusted p=0.0017). We observed different top metabolites in males: Thapsic acid (nominal p= 0.019) and cholesterol (nominal p = 0.035). In a multivariate analysis, seven metabolites were identified in polyps vs controls, adjusting for sex (nominal p<0.05): Nicotinic acid, beta-alanine, 3,4-Dihydroxyhydrocinnamic acid, Isoleucine, Callitrisic acid, Palmitoleic acid, and Thapsic acid.
Conclusion: The different metabolite profiles observed in males versus females provide evidence supporting different carcinogenic mechanisms according to sex, which may contribute to the CRC differences in presentation and outcomes reported. The metabolites detected could be potential biomarker candidates and we will be examining microbiome integration analyses with additional samples and even matching across groups. Together, these efforts will enable a more precise delineation of sex-dependent metabolic pathways that can ultimately inform tailored CRC risk stratification and prevention strategies.
利益披露 Disclosure
M. G. Soto-Santiago, None..
L. A. Casiano Agosto, None..
M. Gonzalez-Pons, None.