YAP1 positive

The present study demonstrated that YAP1 positively regulates aerobic glycolysis by inhibiting EGLN2 expression, which results in an increased HIF-1α protein level and transcriptional activity. YAP1 was positively regulated and significantly correlated with HIF-1α-targeted glycolytic genes, including glucose transporter type 1(GLUT1), hexokinase2 (HK2) and lactate dehydrogenase A (LDHA). Elevated YAP1 expression and concomitant downregulation of EGLN2 contributed to poor survival in patients with pancreatic cancer. Our results suggest that YAP1 may be a promising predictive marker and treatment target for human pancreatic cancer.

The therapeutic vulnerabilities associated with POU2F3 expression in SCLC suggest that a similar approach might be considered for POU2F3-positive carcinomas of the sinonasal tract. Given their diagnostic and possible therapeutic relevance, nNEM have potential to transform the way we approach the diagnosis and management of sinonasal small round epithelial/neuroepithelial malignancies.

In extensive-stage disease (ED), the median OS was 11.3 months for the YAP1-positive group and 11 months for the YAP1-negative group (P=0.03). Positive expression of YAP1 can be associated with durable CR and favorable survival outcomes in patients with SCLC, especially in LD.

Survival and Cox regression analyses indicated that high CPNE3 expression was an independent prognostic marker for GC. This study elucidated the pivotal involvement of an aberrantly activated CPNE3/YAP1 positive feedback loop in the malignant progression of GC, thereby uncovering novel prognostic factors and therapeutic targets in GC.

P=N/A, N=110, Completed, Tianjin Medical University Second Hospital | Recruiting --> Completed | N=60 --> 110 | Trial completion date: May 2023 --> Nov 2023

Finally, aberrant activation of ENO1/YAP1/PLCB1 and decreased HPGD expression in clinical hepatocellular carcinoma samples indicate a potential correlation between ENO1-regulated AA metabolism and cancer development. These findings underline a new function of ENO1 in regulating AA metabolism and tumorigenesis, suggesting a therapeutic potential for aspirin in patients with liver cancer with aberrant expression of ENO1 or YAP1.

Diagnosis by real-time PCR is a relatively fast, accessible and easily interpreted method that allows verification of the molecular group in 70% of cases of supratentorial ependymomas without the use of additional methods.

Our whole-section analysis in resected SCLCs reveals the highly heterogeneous nature of the molecular subtype and its clinicopathologic relevance. Although YAP1 is not a subtype delineator, YAP1 relates to the phenotypic plasticity of SCLC and may serve as a poor prognostic factor in resected SCLC.

This suggests that the ability for cancer cells to acquire YAP1 expression and, perhaps, pLCNEC-like features, may be a resistance mechanism in relapsed SCLC, contributing to the abundant intratumoral heterogeneity and highlighting potential vulnerabilities to overcome resistance. In summary, YAP1 may be a predictive biomarker of intact RB1 and response to cellular and checkpoint immunotherapy and MEK1/CDK4/6 inhibition in pLCNEC and relapsed SCLC.

We found rare extrapulmonary POU2F3-positive tumors arising from previously unappreciated cells of origin. Our data show novel molecular pathologic features of EP-NEC/PDCs including potential therapeutic vulnerabilities, thereby emphasizing the need for focusing on unique features of EP-NEC/PDCs.

P=N/A, N=60, Recruiting, Tianjin Medical University Second Hospital | Trial completion date: May 2020 --> May 2023 | Trial primary completion date: May 2019 --> May 2023

Moreover, patients with high USP49 and YAP1 expression had extremely short overall survival. The findings of this study reveal that the aberrant activation of the USP49/YAP1 positive feedback loop plays a critical role in the malignant progression of GC, thus providing potential novel prognostic factors and therapeutic targets for GC.

And HJURP/YAP1/NDRG1 axis could affect cell proliferation and chemotherapy sensitivity in triple-negative breast cancer. Taken together, these findings provide insights into the transcriptional regulation axis of HJURP/YAP1/NDRG1 in triple-negative breast cancer progression and therapeutic response.

Although rare in primary SCLC, some cases of primary LCNEC have many YAP1-positive cells, which is correlated with chemotherapy resistance. YAP1 staining may be useful in the exclusion diagnosis of SCLC or in the selection of treatment for LCNEC.

Our results demonstrated that inhibiting the UPS using a selective UBA1 inhibitor, TAK-243, is an effective anti-cancer strategy for SCLC. We determined a distinct transcriptomic-stratified (YAP1low and BEND3high) population of SCLC that is sensitive to UBA1-inhibition therapy with TAK-243 as a single agent and a radiosensitizer.

Our results demonstrated that inhibiting the UPS using a selective UBA1 inhibitor, TAK-243, is an effective anti-cancer strategy for SCLC. We determined a distinct transcriptomic-stratified (YAP1 and BEND3) population of SCLC that is sensitive to UBA1-inhibition therapy with TAK-243 as a single agent and a radiosensitizer.

YAP1 expression within the TME might be useful as a predictive biomarker for immune response and a novel immunotherapeutic prognostic biomarker for LUAD.

In addition, treatment with EnzaR-EVs induces the abilities of cancer stemness, lipid metabolism and enzalutamide resistance in its parental cells. Taken together, these results suggest that YAP1 might be a crucial factor involved in the development of enzalutamide resistance and can be an alternative therapeutic target in prostate cancer.

These preliminary findings raise the possibility that neuroendocrine CHE may be genetically distinct from the conventional RHE/CHE spectrum. Further studies are needed to investigate the pathogenetic relationship of fusion-negative cases with this subset and, less likely, with other members of the HE family of tumors.