Analysis of anti-apoptotic PVT1 oncogene and apoptosis-related proteins (p53, Bcl2, PD-1, and PD-L1) expression in thyroid carcinoma.

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 BRAFV600E 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.

MicroRNA-155 and Disease-Related Immunohistochemical Parameters in Cutaneous Melanoma.

Cutaneous melanoma is a severe and life-threatening form of skin cancer with growing incidences. While novel interventions have improved prognoses for these patients, early diagnosis of targeted treatment remains the most effective approach. MicroRNAs have grown to good use as potential biomarkers for early detection and as targets for treatment. miR-155 is well-studied for its role in tumor cell survival and proliferation in various tissues, although its role in melanoma remains controversial. In silico data analysis was performed in the dbDEMC v.3 to identify differentially expressed miRNA. We validated gene targets in melanoma using TarBase v8.0 and miRPath v3.0 and determined protein-protein interactions of the target genes. One hundred forty patients (age range 21-90 years) with cutaneous melanoma who underwent resection were included. Molecular assessment using Real-Time RT-qPCR, clinicopathological associations, and a literature review for the different roles of miR-155 in melanoma were performed. Analysis of the dbDEMC reveals controversial findings. While there is evidence of upregulation of miR-155 in primary and metastatic melanoma samples, others suggest decreased expression in later-stage melanoma and cases with brain metastasis. miR-155 has been overexpressed in prior cases of melanoma and precancerous lesions, and it was found to be dysregulated when compared to benign nevi. While miR-155 expression was associated with favorable outcomes in some studies, others showed an association with metastasis. Patients with high levels of miR-155 also noted reduction after receiving anti-PD-1 treatment, correlated with more prolonged overall survival. In our patient's cohort, 22.9% relapsed during treatment, and 45% developed recurrence, associated with factors such as lymph node infiltration, high mitotic index, and positive staining for CD117. Although overall analysis revealed miR-155 downregulation in melanoma specimens compared to non-cancer tissues, increased expression of miR-155 was associated with cases of superficial spreading melanoma subtype (p = 0.005) and any melanoma with a high mitotic rate (p = 0.010). The analysis did not identify optimum cutoff values to predict relapse, recurrence, or mortality. In conclusion, miR-155 could have, in part, a potential prognostic utility in cutaneous melanoma. Further mechanistic studies are required to unravel the multifunctional role of miR-155 in melanoma.