Prognosis and Characterization of Microenvironment in Cervical Cancer Influenced by Fatty Acid Metabolism-Related Genes

Abstract

Increasing evidence suggests that diverse activation patterns of metabolic signalling pathways may lead to molecular diversity of cervical cancer (CC). But rare research focuses on the alternation of fatty acid metabolism (FAM) in CC. Therefore, we constructed and compared models based on the expression of FAM-related genes from the Cancer Genome Atlas by different machine learning algorithms. The most reliable model was built with 14 significant genes by LASSO-Cox regression, and the CC cohort was divided into low-/high-risk groups by the median of risk score. Then, a feasible nomogram was established and validated by C-index, calibration curve, net benefit, and decision curve analysis. Furthermore, the hub genes among differential expression genes were identified and the post-transcriptional and translational regulation networks were characterized. Moreover, the somatic mutation and copy number variation landscapes were depicted. Importantly, the specific mutation drivers and signatures of the FAM phenotypes were excavated. As a result, the high-risk samples were featured by activated de novo fatty acid synthesis, epithelial to mesenchymal transition, angiogenesis, and chronic inflammation response, which might be caused by mutations of oncogenic driver genes in RTK/RAS, PI3K, and NOTCH signalling pathways. Besides the hyperactivity of cytidine deaminase and deficiency of mismatch repair, the mutations of POLE might be partially responsible for the mutations in the high-risk group. Next, the antigenome including the neoantigen and cancer germline antigens was estimated. The decreasing expression of a series of cancer germline antigens was identified to be related to reduction of CD8 T cell infiltration in the high-risk group. Then, the comprehensive evaluation of connotations between the tumour microenvironment and FAM phenotypes demonstrated that the increasing risk score was related to the suppressive immune microenvironment. Finally, the prediction of therapy targets revealed that the patients with high risk might be sensitive to the RAF inhibitor AZ628. Our findings provide a novel insight for personalized treatment in CC.

Analysis and experimental validation of fatty acid metabolism-related genes prostacyclin synthase (PTGIS) in endometrial cancer

“…Fatty acid metabolism is involved in energy synthesis, production of signaling molecules, and regulation of the tumor microenvironment, thereby influencing tumor progression [ 24 ]. Although the significance of fatty acid metabolism has been extensively investigated in the context of breast and cervical cancer, there exists a noticeable dearth of research concerning the underlying mechanisms governing fatty acid metabolism in the initiation and advancement of EC [ 25 , 26 ]. Consequently, the primary aim of this study was to establish a prognostic model for EC based on genes associated with FAMGs and identify significant therapeutic targets for EC.…”

Personalized Immunotherapy: Advancing processes to extend patient collectives

“…The hypothesis is to determine if this neoantigen DNA vaccine is capable of developing CD4+ and CD8+ T cell responses. These vaccines are comprised of prioritized neoantigens together with personalized mesothelin epitopes (79). The clinical trial NCT03956056 is also targeted toward pancreatic cancer patients to evaluate immune cell responses to neoantigen vaccines co-administered with immunostimulant poly-ICLC.…”

“…Immunotherapy is rarely administered during pregnancy because of concerns about the potential effects on the fetus. For ICIs, seven cases of women becoming pregnant while undergoing ICI treatment have been reported (76)(77)(78)(79)(80)(81), and four cases of ICI therapy beginning during pregnancy, with or without chemotherapy (76,(82)(83)(84). Three of the melanoma mothers showed disease progression after delivery (80,82,83), and one had an emergency Caesarean section at 24 weeks gestation due to tumor progression and died the day after surgery (82).…”

“…During follow-up, none of the children showed signs of tumor metastasis. Three women developed irAE, one with diarrhea (83) and two with hepatotoxicity (79), and one of the latter discontinued ICIs (80). A case report indicated that exposure to ICIs may cause irAE in newborns (82).…”

Combination of multiple omics techniques for a personalized therapy or treatment selection

“…In light of the important role of lipids for signaling as well as for membrane formation, Zhu and coauthor analyzed specimens from bladder cancer identifying a gene signature with 11 lipid-related genes that was able not only to stratify patients better than the currently used system based on clinical characteristics, but also to predict response to immunotherapy ( 78 ). In cervical cancer, a signature based more specifically on fatty acid metabolism identified high risk patients ( 79 ), whereas the sphingolipid metabolism in association with hypoxia stratified patients with pancreatic ductal adenocarcinoma ( 80 ).…”