Potential role of CFLAR in enhancing 5-FU sensitivity and modulating immune cell infiltration in breast cancer DOI Creative Commons

Yuwei Sun,

Weilun Fang,

Jinwu Peng

и другие.

European journal of medical research, Год журнала: 2025, Номер 30(1)

Опубликована: Апрель 10, 2025

Breast cancer (BRCA), the most common malignancy among women, is a highly heterogeneous disease. Chemoresistance major factor leading to treatment failure in BRCA. However, mechanisms underlying development of chemoresistance remain unclear. In this study, we performed comprehensive bioinformatic analysis examine role cell death-associated genes BRCA treatment. Specifically, focused on caspase 8 and Fas-associated protein with death domain-like apoptosis regulator (CFLAR), which was identified as co-differentially expressed molecule potential prognostic values. We then validated these findings through vitro experiments BT- 549 MDA-MB- 231 breast cells. Based bioinformatics analysis, CFLAR expression found be downregulated patients BRCA, whereas its high significantly associated improved prognosis. Kyoto Encyclopedia Genes Genomes (KEGG) pathway indicated that aberrantly potentially oxidative phosphorylation, T receptor signaling, NADH dehydrogenase (ubiquinone) activity. demonstrated overexpression inhibited generation reactive oxygen species (ROS), consequently promoting 5-fluorouracil (5-FU) sensitivity The positively correlated abundance several tumor-infiltrating immune cells, especially CD8 + further supporting regulation. conclusion, study reveals novel roles enhancing chemotherapy patient outcome underscores therapeutic target. These results supported target biomarker patients.

Язык: Английский

Development and external validation of a machine learning-based model to predict postoperative recurrence in patients with duodenal adenocarcinoma: a multicenter, retrospective cohort study DOI Creative Commons
Xu Liu,

Qifeng Xiao,

Zongting Gu

и другие.

BMC Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Фев. 21, 2025

Duodenal adenocarcinoma (DA) has a high recurrence rate, making the prediction of after surgery critically important. Our objective is to develop machine learning-based model predict postoperative DA. We conducted multicenter, retrospective cohort study in China. 1830 patients with DA who underwent radical between 2012 and 2023 were included. Wrapper methods used select optimal predictors by ten learning learners. Subsequently, these learners utilized for development. The model's performance was validated using three separate cohorts, assessed concordance index (C-index), time-dependent calibration curve, receiver operating characteristic curves, decision curve analysis. After selecting predictors, feature subsets identified. And combined permutation, resulting development 100 predictive models, Penalized Regression + Accelerated Oblique Random Survival Forest (PAM) exhibited best performance. C-index PAM 0.882 (95% CI 0.860–0.886) training cohort, 0.747 0.683–0.798) validation 1, 0.736 0.649–0.792) 2, 0.734 0.674–0.791) 3. A publicly accessible web tool developed PAM. potential identify patients. This can assist clinicians assessing severity disease, facilitating patient follow-up, aiding formulation adjuvant treatment strategies.

Язык: Английский

Процитировано

0

Potential role of CFLAR in enhancing 5-FU sensitivity and modulating immune cell infiltration in breast cancer DOI Creative Commons

Yuwei Sun,

Weilun Fang,

Jinwu Peng

и другие.

European journal of medical research, Год журнала: 2025, Номер 30(1)

Опубликована: Апрель 10, 2025

Breast cancer (BRCA), the most common malignancy among women, is a highly heterogeneous disease. Chemoresistance major factor leading to treatment failure in BRCA. However, mechanisms underlying development of chemoresistance remain unclear. In this study, we performed comprehensive bioinformatic analysis examine role cell death-associated genes BRCA treatment. Specifically, focused on caspase 8 and Fas-associated protein with death domain-like apoptosis regulator (CFLAR), which was identified as co-differentially expressed molecule potential prognostic values. We then validated these findings through vitro experiments BT- 549 MDA-MB- 231 breast cells. Based bioinformatics analysis, CFLAR expression found be downregulated patients BRCA, whereas its high significantly associated improved prognosis. Kyoto Encyclopedia Genes Genomes (KEGG) pathway indicated that aberrantly potentially oxidative phosphorylation, T receptor signaling, NADH dehydrogenase (ubiquinone) activity. demonstrated overexpression inhibited generation reactive oxygen species (ROS), consequently promoting 5-fluorouracil (5-FU) sensitivity The positively correlated abundance several tumor-infiltrating immune cells, especially CD8 + further supporting regulation. conclusion, study reveals novel roles enhancing chemotherapy patient outcome underscores therapeutic target. These results supported target biomarker patients.

Язык: Английский

Процитировано

0