PFKP is a prospective prognostic, diagnostic, immunological and drug sensitivity predictor across pan-cancer

Peng, Jian; Li, Pingping; Li, Yuan; Quan, Jichuan; Yao, Yanwei; Duan, Junfang; Liu, Xuemei; Li, Hao; Yuan, Dajiang; Wang, Xiaoru

doi:10.1038/s41598-023-43982-2

Cited by 2 publications

(2 citation statements)

References 104 publications

(109 reference statements)

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“…Thirdly, the oncogenic role of PFKP was confirmed by organoids and PDX models in HNSCC. Our findings, along with others [ 11 , 42 ], indicate that PFKP may be a pivotal factor in HNSCC tumorigenesis and progression, making it a potential therapeutic target for HNSCC.…”

Section: Discussionsupporting

confidence: 82%

“…PFKP is the predominant isoform of PFK-1 in various types of tumors [ 8 – 10 ]. Upregulation of PFKP is strongly associated with tumor progression and is a significant indicator of an unfavorable prognosis in breast cancer, glioblastoma, and leukemia [ 8 , 10 , 11 ]. A substantial body of research has demonstrated the critical role of PFKP in promoting aerobic glycolysis within cancer cells, consequently driving cancer cell proliferation and metastasis [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

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A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression

Liu,

Ding,

Tao

et al. 2024

Mol Cancer

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Background The aberrant expression of phosphofructokinase-platelet (PFKP) plays a crucial role in the development of various human cancers by modifying diverse biological functions. However, the precise molecular mechanisms underlying the role of PFKP in head and neck squamous cell carcinoma (HNSCC) are not fully elucidated. Methods We assessed the expression levels of PFKP and c-Myc in tumor and adjacent normal tissues from 120 HNSCC patients. A series of in vitro and in vivo experiments were performed to explore the impact of the feedback loop between PFKP and c-Myc on HNSCC progression. Additionally, we explored the therapeutic effects of targeting PFKP and c-Myc in HNSCC using Patient-Derived Organoids (PDO), Cell Line-Derived Xenografts, and Patients-Derived Xenografts. Results Our findings indicated that PFKP is frequently upregulated in HNSCC tissues and cell lines, correlating with poor prognosis. Our in vitro and in vivo experiments demonstrate that elevated PFKP facilitates cell proliferation, angiogenesis, and metastasis in HNSCC. Mechanistically, PFKP increases the ERK-mediated stability of c-Myc, thereby driving progression of HNSCC. Moreover, c-Myc stimulates PFKP expression at the transcriptional level, thus forming a positive feedback loop between PFKP and c-Myc. Additionally, our multiple models demonstrate that co-targeting PFKP and c-Myc triggers synergistic anti-tumor effects in HNSCC. Conclusion Our study demonstrates the critical role of the PFKP/c-Myc positive feedback loop in driving HNSCC progression and suggests that simultaneously targeting PFKP and c-Myc may be a novel and effective therapeutic strategy for HNSCC.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression

Liu,

Ding,

Tao

et al. 2024

Mol Cancer

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Development of a biomarker prediction model for post-trauma multiple organ failure/dysfunction syndrome based on the blood transcriptome

Duran,

Banerjee,

Flaherty

et al. 2024

Ann. Intensive Care

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Background Multiple organ failure/dysfunction syndrome (MOF/MODS) is a major cause of mortality and morbidity among severe trauma patients. Current clinical practices entail monitoring physiological measurements and applying clinical score systems to diagnose its onset. Instead, we aimed to develop an early prediction model for MOF outcome evaluated soon after traumatic injury by performing machine learning analysis of genome-wide transcriptome data from blood samples drawn within 24 h of traumatic injury. We then compared its performance to baseline injury severity scores and detection of infections. Methods Buffy coat transcriptome and linked clinical datasets from blunt trauma patients from the Inflammation and the Host Response to Injury Study (“Glue Grant”) multi-center cohort were used. According to the inclusion/exclusion criteria, 141 adult (age ≥ 16 years old) blunt trauma patients (excluding penetrating) with early buffy coat (≤ 24 h since trauma injury) samples were analyzed, with 58 MOF-cases and 83 non-cases. We applied the Least Absolute Shrinkage and Selection Operator (LASSO) and eXtreme Gradient Boosting (XGBoost) algorithms to select features and develop models for MOF early outcome prediction. Results The LASSO model included 18 transcripts (AUROC [95% CI]: 0.938 [0.890–0.987] (training) and 0.833 [0.699–0.967] (test)), and the XGBoost model included 41 transcripts (0.999 [0.997–1.000] (training) and 0.907 [0.816–0.998] (test)). There were 16 overlapping transcripts comparing the two panels (0.935 [0.884–0.985] (training) and 0.836 [0.703–0.968] (test)). The biomarker models notably outperformed models based on injury severity scores and sex, which we found to be significantly associated with MOF (APACHEII + sex—0.649 [0.537–0.762] (training) and 0.493 [0.301–0.685] (test); ISS + sex—0.630 [0.516–0.744] (training) and 0.482 [0.293–0.670] (test); NISS + sex—0.651 [0.540–0.763] (training) and 0.525 [0.335–0.714] (test)). Conclusions The accurate assessment of MOF from blood samples immediately after trauma is expected to aid in improving clinical decision-making and may contribute to reduced morbidity, mortality and healthcare costs. Moreover, understanding the molecular mechanisms involving the transcripts identified as important for MOF prediction may eventually aid in developing novel interventions.

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PFKP is a prospective prognostic, diagnostic, immunological and drug sensitivity predictor across pan-cancer

Cited by 2 publications

References 104 publications

A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression

A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression

Development of a biomarker prediction model for post-trauma multiple organ failure/dysfunction syndrome based on the blood transcriptome

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