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Plasma fatty acids depletion: a metabolic signature related to colon cancer

ABSTRACT: Understanding the complex interplay between tumor biology and host metabolism presents a formidable challenge with important clinical implications. At the local level, metabolic alterations of tumor cells and tumor microenvironment is a well-recognized process and constitute one of the major hallmarks of cancer cells. Consequently, research has largely isolated tumor biology from systemic metabolic dynamics, overlooking their potential interrelation. Nonetheless, cancer pathology is also very clearly associated with broad systemic metabolic disturbances, as exemplified by the frequent development of cachexia, which reaches up to 40% of colon cancer (CC) patients. Other metabolic alterations observed associated with cancer include insulin resistance, hypercalcemia, and amino acid metabolism, which underline the extensive systemic impact of cancer on the metabolic networks. In addition to these alterations, another interesting yet less studied phenomenon in cancer pathology is the observation that cancer patients present alterations of their typical fatty acid profiles in circulation. Evidence of this phenomenon is limited and scattered across the literature, although some studies have identified this alteration in patients with colorectal and liver cancer. Nonetheless, discerning whether these lipid profile shifts signify an intrinsic metabolic alteration or are secondary to factors such as malnutrition, adipose tissue dynamics, or clinical parameters like tumor staging and location has yet to be determined. It is evident that addressing this issue requires a more comprehensive analysis of the possible factors involved. Our study adopted an integrative methodology to study this process in CC, combining advanced body composition analysis, nutritional assessments, extensive clinical and transcriptomic data of the tumor, and precise profiling of esterified fatty acids in plasma. This multifaceted strategy has enabled us to confirm that the alteration of FA levels is a frequent phenomenon in patients with CC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE267846 | GEO | 2025/05/28

REPOSITORIES: GEO

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Project description:Cervical cancer (CC) is one of the most common malignancy in women worldwide. It is characterized by a natural continuous phenomenon, that is, it is in the initial stage of HPV infection, progresses to intraepithelial neoplasia, and then develops into invasion and metastasis. Determining the complexity of tumor microenvironment (TME) can deepen our understanding of lesion progression and provide novel therapeutic strategies for CC. We performed the single-cell RNA sequencing on the normal cervix, intraepithelial neoplasia, primary tumor and metastatic lymph node tissues to describe the composition, lineage, and functional status of immune cells and mesenchymal cells at different stages of CC progression. A total of 59913 single cells were obtained and divided into 9 cellular clusters, including immune cells (T/NK cells, macrophages, B cells, plasma cells, mast cells and neutrophils) and mesenchymal cells (endothelial cells, smooth muscle cells and fibroblasts). Our results showed that there were distinct cell subpopulations in different stages of CC. High-stage intraepithelial neoplasia (HSIL) tissue exhibited a low, recently activated TME, and it was characterized by high infiltration of tissue-resident CD8 T cell, effector NK cells, Treg, DC1, pDC, and M1-like macrophages. Tumor tissue displayed high enrichment of exhausted CD8 T cells, resident NK cells and M2-like macrophages, suggesting immunosuppressive TME. Metastatic lymph node consisted of naive T cell, central memory T cell, circling NK cells, cytotoxic CD8+ T cells and effector memory CD8 T cells, suggesting an early activated phase of immune response. This study is the first to delineate the transcriptome profile of immune cells during CC progression using single-cell RNA sequencing. Our results indicated that HSIL exhibited a low, recently activated TME, tumor displayed immunosuppressive statue, and metastatic lymph node showed early activated phase of immune response. Our study enhanced the understanding of dynamic change of TME during CC progression and has implications for the development of novel treatments to inhibit the initiation and progression of CC.

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Plasma fatty acids depletion: a metabolic signature related to colon cancer

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