Department of Colorectal Surgery, Cork University Hospital, Cork, Ireland.
Department of Academic Surgery, Cork University Hospital, Cork, Ireland.
J Gastrointest Cancer. 2023 Mar;54(1):247-258. doi: 10.1007/s12029-022-00813-3. Epub 2022 Mar 3.
Metabolomic analysis in colorectal cancer (CRC) is an emerging research area with both prognostic and therapeutic targeting potential. We aimed to identify metabolomic pathway activity prognostic for CRC recurrence and overall survival and cross-reference such metabolomic data with prognostic genomic single-nucleotide polymorphisms (SNPs).
A systematic search of PubMed, Embase and Cochrane Library was performed for studies reporting prognostic metabolomic pathway activity in CRC in keeping with PRISMA guidelines. The QUADOMICS tool was used to assess study quality. MetaboAnalyst software (version4.0) was used to map metabolites that were associated with recurrence and survival in CRC to recognise metabolic pathways and identify genomic SNPs associated with CRC prognosis, referencing the following databases: Human Metabolome Database (HMDB), the Small Molecule Pathway Database (SMPDB), PubChem and Kyoto Encyclopaedia of Genes and Genomes (KEGG) Pathway Database.
Nine studies met the inclusion criteria, reporting on 1117 patients. Increased metabolic activity in the urea cycle (p = 0.002, FDR = 0.198), ammonia recycling (p = 0.004, FDR = 0.359) and glycine and serine metabolism (p = 0.004, FDR = 0.374) was prognostic of CRC recurrence. Increased activity in aspartate metabolism (p < 0.001, FDR = 0.079) and ammonia recycling (p = 0.004, FDR = 0.345) was prognostic of survival. Eight resulting SNPs were prognostic for CRC recurrence (rs2194980, rs1392880, rs2567397, rs715, rs169712, rs2300701, rs313408, rs7018169) and three for survival (rs2194980, rs169712, rs12106698) of which two overlapped with recurrence (rs2194980, rs169712).
With a caveat on study heterogeneity, specific metabolites and metabolic pathway activity appear evident in the setting of poor prognostic colorectal cancers and such metabolic signatures are associated with specific genomic SNPs.
代谢组学分析在结直肠癌（CRC）中是一个新兴的研究领域，具有预后和治疗靶向的潜力。我们旨在确定对 CRC 复发和总生存具有预后意义的代谢组学途径活性，并将此类代谢组学数据与预后基因组单核苷酸多态性（SNP）交叉参考。
根据 PRISMA 指南，系统地检索了 PubMed、Embase 和 Cochrane Library 中报道 CRC 中具有预后意义的代谢组学途径活性的研究。使用 QUADOMICS 工具评估研究质量。使用 MetaboAnalyst 软件（版本 4.0）将与 CRC 复发和生存相关的代谢物映射到识别代谢途径，并识别与 CRC 预后相关的基因组 SNP，参考以下数据库：人代谢组数据库（HMDB）、小分子途径数据库（SMPDB）、PubChem 和京都基因与基因组百科全书（KEGG）途径数据库。
符合纳入标准的 9 项研究报告了 1117 名患者的数据。尿素循环（p=0.002， FDR=0.198）、氨回收（p=0.004，FDR=0.359）和甘氨酸和丝氨酸代谢（p=0.004，FDR=0.374）的代谢活性增加与 CRC 复发具有预后意义。天冬氨酸代谢（p<0.001，FDR=0.079）和氨回收（p=0.004，FDR=0.345）的活性增加与生存具有预后意义。有 8 个由此产生的 SNP 与 CRC 复发具有预后意义（rs2194980、rs1392880、rs2567397、rs715、rs169712、rs2300701、rs313408、rs7018169），3 个与生存具有预后意义（rs2194980、rs169712、rs12106698），其中 2 个与复发重叠（rs2194980、rs169712）。
尽管存在研究异质性，但在预后不良的结直肠癌中，特定代谢物和代谢途径活性显然存在，并且这些代谢特征与特定的基因组 SNP 相关。
