Utilizing multimodal mass spectrometry imaging for profiling immune cell composition and N-glycosylation across colorectal carcinoma disease progression.
Utilizing multimodal mass spectrometry imaging for profiling immune cell composition and N-glycosylation across colorectal carcinoma disease progression.
复制标题
DOI：
10.3389/fphar.2023.1337319
复制
发表时间：
2023
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
结直肠癌（CRC）是世界范围内的主要死亡原因，通常由特定的基因突变引起，从癌前腺瘤进展为腺癌。通过定期筛查的早期发现可以使患者的5年生存率达到90%。然而，不幸的是，只有一小部分CRC病例在浸润前阶段被确定，允许进展在10-15年内悄然发生。肿瘤微环境中免疫系统和肿瘤细胞之间错综复杂的相互作用在CRC的进展中起着关键作用。免疫细胞簇可以抑制或促进肿瘤的发生、生长和转移。为了更好地理解这种关系，我们使用基质辅助激光解吸电离质谱成像（MALDI-MSI）进行了N-糖组学分析。我们在所有样本中检测到近100种N-聚糖，揭示了N-聚糖谱从正常组织到癌组织的转变，其标志是高甘露糖N-聚糖的减少。癌前浸润性癌的进一步分析显示，随着疾病进展，寡甘露糖双触角和四触角N-聚糖增加。此外，在非粘液性和粘液性CRC组织之间观察到N-糖组谱的明显分层，这是由少甘露糖、高甘露糖和平分N-聚糖驱动的。值得注意的是，我们鉴定了CD 20 + B细胞和CD 3/CD 44 + T细胞的免疫簇，其具有二等分和分支N-聚糖的特征谱。这些空间N-聚糖谱在CRC的整个进展过程中提供了潜在的生物标志物和治疗靶点。
Colorectal cancer (CRC) stands as a leading cause of death worldwide, often arising from specific genetic mutations, progressing from pre-cancerous adenomas to adenocarcinomas. Early detection through regular screening can result in a 90% 5-year survival rate for patients. However, unfortunately, only a fraction of CRC cases are identified at pre-invasive stages, allowing progression to occur silently over 10–15 years. The intricate interplay between the immune system and tumor cells within the tumor microenvironment plays a pivotal role in the progression of CRC. Immune cell clusters can either inhibit or facilitate tumor initiation, growth, and metastasis. To gain a better understanding of this relationship, we conducted N-glycomic profiling using matrix-assisted laser desorption-ionization mass spectrometry imaging (MALDI-MSI). We detected nearly 100 N-glycan species across all samples, revealing a shift in N-glycome profiles from normal to cancerous tissues, marked by a decrease in high mannose N-glycans. Further analysis of precancerous to invasive carcinomas showed an increase in pauci-mannose biantennary, and tetraantennary N-glycans with disease progression. Moreover, a distinct stratification in the N-glycome profile was observed between non-mucinous and mucinous CRC tissues, driven by pauci-mannose, high mannose, and bisecting N-glycans. Notably, we identified immune clusters of CD20+ B cells and CD3/CD44+ T cells distinctive and predictive with signature profiles of bisecting and branched N-glycans. These spatial N-glycan profiles offer potential biomarkers and therapeutic targets throughout the progression of CRC.
登录
查看更多内容
影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
4.6
作者：
Doherty M;Theodoratou E;Walsh I;Adamczyk B;Stöckmann H;Agakov F;Timofeeva M;Trbojević-Akmačić I;Vučković F;Duffy F;McManus CA;Farrington SM;Dunlop MG;Perola M;Lauc G;Campbell H;Rudd PM
通讯作者：
Rudd PM
影响因子：
168.9
作者：
Cunningham, David;Atkin, Wendy;Starling, Naureen
通讯作者：
Starling, Naureen
影响因子：
--
作者：
de Vroome SW;Holst S;Girondo MR;van der Burgt YEM;Mesker WE;Tollenaar RAEM;Wuhrer M
通讯作者：
Wuhrer M
影响因子：
4.2
作者：
Coura MMA;Barbosa EA;Brand GD;Bloch C Jr;de Sousa JB
通讯作者：
de Sousa JB