The biochemistry of cancer cells diverges significantly from normal cells as a result of a comprehensive reprogramming of metabolic pathways. A major factor influencing cancer metabolism is hypoxia, which is mediated by HIF1α and HIF2α. HIF1α represents one of the principal regulators of metabolism and energetic balance in cancer cells through its regulation of glycolysis, glycogen synthesis, Krebs cycle and the pentose phosphate shunt. However, less is known about the role of HIF1α in modulating lipid metabolism. Lipids serve cancer cells to provide molecules acting as oncogenic signals, energetic reserve, precursors for new membrane synthesis and to balance redox biological reactions. To study the role of HIF1α in these processes, we used HCT116 colorectal cancer cells expressing endogenous HIF1α and cells in which the hif1α gene was deleted to characterize HIF1α-dependent and independent effects on hypoxia regulated lipid metabolites. Untargeted metabolomics integrated with proteomics revealed that hypoxia induced many changes in lipids metabolites. Enzymatic steps in fatty acid synthesis and the Kennedy pathway were modified in a HIF1α-dependent fashion. Palmitate, stearate, PLD3 and PAFC16 were regulated in a HIF-independent manner. Our results demonstrate the impact of hypoxia on lipid metabolites, of which a distinct subset is regulated by HIF1α.
The role of Fyn‐related kinase (FRK) in malignant tumors remains controversial. Our study investigated the function of FRK in lung cancer. Immunohistochemistry staining and generating a knockout of FRK by CRISPR/Cas9 in H1299 (FRK‐KO‐H1299) cells were strategies used to explore the role of FRK. Immunohistochemistry staining indicated that FRK expression was elevated in 223 lung cancer tissues compared to 26 distant normal lung tissues. FRK contributed to poor survival status in lung cancer patients and acted as a predictor for poor prognosis of lung cancer. Knockout of FRK by CRISPR/Cas9 markedly inhibited proliferation, invasion, colony formation and epithelial–mesenchymal transition (EMT) process in the lung cancer cell line H1299. Further exploration indicated that FRK‐KO damaged the stemness phenotype of H1299 by inhibiting CD44 and CD133 expression. Seahorse detection and a U‐13C flux assay revealed that FRK‐KO induced metabolism reprogramming by inhibiting the Warburg effect and changing the energy type in H1299 cells. Epidermal growth factor stimulation recovered the expression of FRK and biological functions, metabolic reprogramming and stemness phenotype of H1299 cells. FRK plays an oncogenic role in lung cancer cells via a novel regulation mechanism of enhancing the stemness of H1299 cells by inducing metabolism reprogramming, which finally promotes EMT and metastasis. Our study also indicates that FRK could be used as a potential therapeutic target for drug development.
Background Suicidal ideation in cancer patients is a critical challenge. At present, few studies focus on factors associated with suicidal ideation, and predictive models are still lacking. This study aimed at investigating the risk factors for suicidal ideation among cancer patients, and developed a predictive nomogram to screen high risk cancer patients for early prevention and intervention. Methods A questionnaire survey was conducted among cancer patients between May 2021 and January 2022. The factors associated with suicidal ideation were used to construct a multivariate logistic regression model, which was visualized as a predictive nomogram to evaluate the risk of suicidal ideation. Areas under the curve, calibration plot, decision curve analysis, and internal and external validation were used to validate the discrimination, calibration and clinical usefulness of the model. Results A total of 820 patients with cancer were recruited for this study and 213 (25.98%) developed suicidal ideation. Levels of demoralization, depression and cancer staging, marital status, residence, medical financial burden, and living condition were influence factors for suicidal ideation. Comparing nomogram with Self-rating Idea of Suicide Scale (SIOSS), the nomogram had a satisfactory discrimination ability with an AUC of 0.859 (95% CI: 0.827–0.890) and 0.818 (95% CI: 0.764–0.873) in the training and validation sets, respectively. The calibration plot and decision curve analysis revealed that this nomogram was in good fitness and could be beneficial in clinical applications. Conclusions Suicidal ideation is common in cancer patients. Levels of demoralization, depression and cancer staging were independent predictors of suicidal ideation. The nomogram is an effective and simple tool for predictive suicidal ideation in cancer patients.
Purpose Suicidal ideation (SI) is often overlooked as a risk factor for people with cancer. Because it is often a precursor for suicidal behavior, it is critical to identify and address SI in a timely manner. This study investigated SI incidence and risk factors in a cohort of Chinese patients with mixed cancer types. Methods Data from this cross-sectional study were collected from 588 patients receiving medical therapy for tumors at Nanfang Hospital and the Integrated Hospital of Traditional Chinese Medicine at Southern Medical University. SI was measured using the Self-rating Idea of Suicide Scale (SIOSS). Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). The Chinese version of the Demoralization Scale II (DS-II-C) was used to assess demoralization. Univariate and correlation analyses were used to identify correlative factors of SI and multiple stepwise linear regression analysis was used to characterize potential risk factors. Results SI was reported in 24.7% of participants and the SIOSS score was 14.00 (13.00, 15.00) in the SI group. Multiple linear regression results showed that demoralization, medical financial burden, cancer type, living condition, caretaker, working state, residence, gender, and marital status explained 32.1% of the SI in this cohort (F = 28.705, P < 0.001). Conclusion Approximately one-quarter of cancer patients in this study reported SI influenced by both external and internal factors. Characterizing these factors can be informative for prevention and treatment efforts.
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