Open AccessAnalysis of anti‐apoptotic PVT1 oncogene and apoptosis‐related proteins (p53, Bcl2, PD‐1, and PD‐L1) expression in thyroid carcinoma
Author(s) -
Ibrahiem Afaf T.,
Makhdoom Amin K.,
Alanazi Khalid S.,
Alanazi Abdulaziz M.,
Mukhlef Abdulaziz M.,
Elshafey Saad H.,
Toraih Eman A.,
Fawzy Manal S.
Publication year - 2022
Publication title -
journal of clinical laboratory analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 50
eISSN - 1098-2825
pISSN - 0887-8013
DOI - 10.1002/jcla.24390
Subject(s) - pvt1 , apoptosis , immunohistochemistry , oncogene , medicine , cancer research , downregulation and upregulation , cancer , survival analysis , pathology , oncology , biology , long non coding rna , gene , cell cycle , biochemistry
Abstract Background An aberrant expression of long non‐coding RNA PVT1 has been associated with apoptosis in various cancer types. We aimed to explore the PVT1 and four apoptosis‐related proteins (p53, Bcl2, and PD‐1/PD‐L1) signature in thyroid cancer (TC). Methods The PVT1 expression level was measured in 64 FFPE TC paired samples by real‐time quantitative PCR. Overall and stratified analyses by different clinicopathological features were done. The apoptotic proteins were evaluated by immunohistochemistry staining. Results Overall analysis showed significant PVT1upregulation in TC tissues ( p < 0.001). Similarly, subgroup analysis by BRAF V600E mutation showed consistent results. Lower expression of p53 was associated with mortality ( p = 0.001). Bcl2 overexpression was associated with greater tumor size ( p = 0.005). At the same time, HCV‐positive cases were associated with repressed Bcl2 expression levels (54.3% in HCV‐negative vs . 6.9% in HCV‐positive cases, p = 0.011). PD‐1 expression was associated with lymph node metastasis ( p = 0.004). Enhanced PD‐L1 expression in the tumor was associated with a higher tumor stage, lymphovascular invasion, and mortality risk. Kaplan–Meier curves for overall survival showed that low p53 and high PD‐L1 expressions were associated with lower survival time. The p53‐positive staining is associated with a 90% decreased mortality risk (HR = 0.10, 95%CI = 0.02–0.47, p = 0.001), while patients with high PD‐L1 were five times more likely to die (HR = 4.74, 95%CI = 1.2–18.7, p = 0.027). Conclusion Our results confirm the upregulation of PVT1 in TC. The apoptosis‐related proteins (p53, Bcl2, and PD‐1/PD‐L1) showed different prognostic utility in TC patients; in particular, low p53 and high PD‐L1 expressions associated with low survival times. Further large‐scale and mechanistic studies are warranted.