CDKN2A expression

P1, N=85, Active, not recruiting, Cue Biopharma | Trial completion date: Dec 2023 --> May 2025 | Trial primary completion date: Sep 2023 --> Nov 2024

We developed the I2 index to quantify impairments across geriatric domains and discovered that PBTL p16, Hannum, PhenoAge, and DunedinPACE are promising indicators of frailty in HM.

HPV positivity is rare in NSCLC among a Jordanian subpopulation. P16 INK4a reliability as a surrogate marker for HPV infection in lung cancer must be revisited.

Finally, tumors with p16 knockdown were more sensitive to the anti-folate methotrexate in vivo than control tumors. Together, our data provide evidence to reevaluate the utility of these drugs in patients with p16/CDKN2Alow tumors as loss of p16/CDKN2A may provide a therapeutic window for these agents.

P2, N=30, Recruiting, Washington University School of Medicine | Trial completion date: Oct 2025 --> Oct 2027 | Trial primary completion date: Oct 2025 --> Oct 2027

Moreover, we discovered that CDKN2A expression was linked to a dysfunctional tumor immune microenvironment. The study shows that CDKN2A, a cuproptosis-related gene, can be used as a prognostic marker for thyroid cancer.

Serum P16ink4A may likely be associated with cervical lesions especially CC in our study population and this may aid detection of such lesions. Diagnostic utility studies for circulating P16ink4A in detection of cervical cancer are recommended.

P16INK4A positive staining, early stages, negative cervical lymph node infiltration, and free-surgical margins are associated with better prognosis in OSCC patients. The study emphasizes the importance of early detection and the potential use of p16INK4A and other clinical variables to stratify OSCC patients with high risks of recurrence and worse overall survivals.

HSV and p16INK4A positivity in relation to diagnosis of the biopsies showed statistically most often p16INK4A in OLP and fibroma. The results of co-expression of p16INK4A and HSV in mucocele and fibroma in oral mucosa suggest a cooperation between the molecular alterations induced by these two viruses. Squamous papilloma samples positive for p16INK4A were also positive for HSV, suggesting that the putative pro-oncogenic action of HSV could be an early event.

Our findings demonstrate that CDKN2A downregulation in glioblastoma cells is associated with decreased cell viability, enhanced drug resistance, increased self-renewal capacity, and altered expression of pluripotency markers. The observed CDKN2A expression changes are mediated by promoter methylation. These results highlight the potential role of CDKN2A as a therapeutic target and prognostic marker in glioblastoma.

Additionally, Tfcp2l1 can replicate the hypoxic effect of increasing cellular reprogramming. Altogether, our data suggest that the activation of Tfcp2l1 by hypoxia contributes to immortalization prior to malignant transformation, facilitating tumorigenesis and dedifferentiation by regulating Sox2, Sox9, and Jarid2.

Changes in CDKN2A gene expression can be used to predict the response of CRC patients to 5-FU therapy. Additionally, inhibiting CDKN2A activation with Villosol may present a new approach to overcoming 5-FU resistance in clinical settings.

CDKN2A is a prognostic factor and therapeutic target in EC, and is likely associated with the tumor immune landscape and autophagy.

CDKN2A upregulation extensively enhances the carcinogenesis and progression of SCLC.

These results indicate that BCL11b may be involved in CD30 differentiation and PTCL prognosis. The detection and targeting of BCL11b and CD30 may provide new strategies for the treatment and classification of PTCL.

Our study revealed that high CDKN2A expression in CRC is a potentially valuable prognostic biomarker, which may guide PD-1-mediated immunotherapy.

The results indicate the relationship between miR-10b and -155 and the presence of lymph node metastases in OSCC patients, so these miRNAs can be considered as prognostic markers of the disease.

However, there was negative regulation of miR-484 and CDKN2A, and CDKN2A could partially offset the effect of miR-484. MiR-484 promoted cell migration, invasion and angiogenesis by inhibiting CDKN2A expression.

Altogether, a novel four-EMT-related genes signature was a potential biomarker for EC prognosis. These findings might help to ameliorate the individualized prognostication and therapeutic treatment of EC patients.

P1, N=85, Active, not recruiting, Cue Biopharma | Recruiting --> Active, not recruiting | Trial primary completion date: Jun 2023 --> Sep 2023

HPV status alone seems to be lacking prognostic relevance. In contrast, p16 status was confirmed as an independent prognostic factor. Thus, the expression of p16INK4a is associated with a significantly better MFS. Especially in HPV-negative tumours, the p16 status should be evaluated with regard to the prognostic value and thus also with a view to the treatment decision.

Asymptomatic lesions with typical histological features and intact BAP1 and MTAP appear to have a low risk of progression. Cases with WDPMT morphology but loss of BAP1 should be classified as papillary MIS. There is a risk of progression to mesothelioma.

No abstract available

The area under the receiver operating characteristic (ROC) curve (AUC) of the nomogram was significantly higher than the AUC of the CRG score at 7 years. The CRG score, combined with other clinical features, could afford a practical long-term outcome predictor in patients with ER+ EBC.

We therefore addressed this knowledge gap through multi-omic interrogation of tumours from patients enrolled into arm 4 of the Mesothelioma Stratified Therapy umbrella trial (NCT03654833, MiST4), a multi-centre single arm phase IIA trial of atezolizumab and bevacizumab in patients with relapsed mesothelioma. We propose a model in which interacting tumour intrinsic and extrinsic factors correlate with response to PDL1-VEGF inhibition in patients with mesothelioma. Gut microbiota composition represents a new, potentially modifiable target with potential to improve immunotherapy outcomes in patients with mesothelioma. Clinical trial information: NCT03654833.

Furthermore, we demonstrate that in response to ALDH1A3 inhibition, CDKN2A loss skewed cell fate from senescence to apoptosis. Dissecting the role of ALDH1A3 isoform in MPM cells and tumour microenvironment can open new fronts in the treatment of this cancer.

The study deeply defined the concrete roles of cuproptosis-related gene CDKN2A in tumorigenesis. The results provided new insights and pieces of evidence for treatment.

P1, N=85, Recruiting, Cue Biopharma | Trial completion date: Aug 2023 --> Dec 2023 | Trial primary completion date: Feb 2023 --> Jun 2023

p16INK4a expression in the skin is not associated with frailty level or treatment outcome in intermediate fit and frail NDMM patients. Recent literature suggests that p16INK4a mRNA expression in peripheral T cells could be a more accurate marker for cellular senescence. Based on our results, we discourage the evaluation of p16INK4a protein levels in skin biopsies to improve frailty assessment in older patients with newly diagnosed MM.

 This proof-of-concept study shows that invading prostate cancer cells frequently show signs of cellular senescence. This finding may open new avenues for neoadjuvant and adjuvant treatment concepts in men with locally advanced prostate cancer.

Increasing expression of Cdkn2a in control ovaries over time suggests a critical and yet unstudied role for senescence in folliculogenesis. The increasing expression of Cdkn2a in AKA ovaries suggests a potential role for senescence in endometriosis progression and, potentially, attenuation of the development of ovarian cancer. Primary granulosa cells offer an additional model to study these innovative results further.

Furthermore, expression quantitative trait locus analysis demonstrated that the expression of CDKN2A was dependent on the genotype of rs77283072. Taken together, the findings of the present study provided novel insights into the mechanism underlying how the genetic variation in this locus was able to influence breast cancer susceptibility and further the treatment for this disease.

And plicamycin inhibits the progression of HNSCC in cellular assays. In conclusion, this study elucidated a potential mechanism of action of the cuproptosis-associated gene CDKN2A in HNSCC and revealed that plicamycin targets CDKN2A to improve the prognosis of patients.

P=N/A, N=110, Active, not recruiting, Manchester University NHS Foundation Trust | Trial completion date: Jun 2022 --> Oct 2023 | Trial primary completion date: Jun 2022 --> Oct 2023

Last, our study revealed the synergism between ACTR5/IES6-targeting and pharmacological inhibition of CDK in treating HCC. These results indicate that the dynamic interplay between epigenetic regulators, tumor suppressors, and cell cycle machinery could provide novel opportunities for combinational HCC therapy.

The significant increase of p16 INK4A expression level in peripheral immune cells represents potential for use as a CRC screening marker.

We identified that homozygous deletion of CDKN2a to be a predictor of response in most UroA subtype tumors, while some cell lines were inherently resistant possibly from elevated EGFR expression. Identifying gene signatures that are predictive of response will be useful in identifying patients that are likely to respond to IFNα therapy.

TISIDB analysis indicated that AKT1, CD44, and CDKN2A expression had a strong relationship with immune infiltration in lung adenocarcinoma. These hub genes, AKT1, CD44, and CDKN2A, may represent tumor biomarkers that may contribute to the understanding, diagnosis, and treatment of lung adenocarcinoma.