Differential analysis of histopathological and genetic markers of cancer aggressiveness, and survival difference in EBV-positive and EBV-negative prostate carcinoma

Authors

Khalid Ahmed, Aga Khan University
Ali Sheikh salman Sheikh, Aga Khan UniversityFollow
Tahira Ghulam, Aga Khan UniversityFollow
Ghulam Haider, Aga Khan UniversityFollow
Kulsoom Ghias, Aga Khan UniversityFollow
Saira Fatima, Aga Khan UniversityFollow
Farhat Abbas, Aga Khan UniversityFollow
Muhammad Nouman Mughal, Aga Khan UniversityFollow
Syed Hani Abidi, Aga Khan UniversityFollow
Antonio Sarria Santamera, Nazarbayev University, Kazakhstan

Document Type

Article

Department

Biological and Biomedical Sciences

Abstract

Several studies have shown an association between prostate carcinoma (PCa) and Epstein-Barr virus (EBV); however, none of the studies so far have identified the histopathological and genetic markers of cancer aggressiveness associated with EBV in PCa tissues. In this study, we used previously characterized EBV-PCR-positive (n = 39) and EBV-negative (n = 60) PCa tissues to perform an IHC-based assessment of key histopathological and molecular markers of PCa aggressiveness (EMT markers, AR expression, perineural invasion, and lymphocytic infiltration characterization). Additionally, we investigated the differential expression of key oncogenes, EMT-associated genes, and PCa-specific oncomiRs, in EBV-positive and -negative tissues, using the qPCR array. Finally, survival benefit analysis was also performed in EBV-positive and EBV-negative PCa patients. The EBV-positive PCa exhibited a higher percentage (80%) of perineural invasion (PNI) compared to EBV-negative PCa (67.3%) samples. Similarly, a higher lymphocytic infiltration was observed in EBV-LMP1-positive PCa samples. The subset characterization of T and B cell lymphocytic infiltration showed a trend of higher intratumoral and tumor stromal lymphocytic infiltration in EBV-negative tissues compared with EBV-positive tissues. The logistic regression analysis showed that EBV-positive status was associated with decreased odds (OR = 0.07; p-value < 0.019) of CD3 intratumoral lymphocytic infiltration in PCa tissues. The analysis of IHC-based expression patterns of EMT markers showed comparable expression of all EMT markers, except vimentin, which showed higher expression in EBV-positive PCa tissues compared to EBV-negative PCa tissues. Furthermore, gene expression analysis showed a statistically significant difference (p < 0.05) in the expression of CDH1, AR, CHEK-2, CDKN-1B, and CDC-20 and oncomiRs miR-126, miR-152-3p, miR-452, miR-145-3p, miR-196a, miR-183-3p, and miR-146b in EBV-positive PCa tissues compared to EBV-negative PCa tissues. Overall, the survival proportion was comparable in both groups. The presence of EBV in the PCa tissues results in an increased expression of certain oncogenes, oncomiRs, and EMT marker (vimentin) and a decrease in CD3 ITL, which may be associated with the aggressive forms of PCa.

Comments

Pagination is not provided by author/publisher.

Publication (Name of Journal)

Scientific Reports

DOI

10.1038/s41598-024-60538-0

Recommended Citation

Ahmed, K., Sheikh, A. s., Ghulam, T., Haider, G., Ghias, K., Fatima, S., Abbas, F., Mughal, M. N., Abidi, S. H., Santamera, A. S. (2024). Differential analysis of histopathological and genetic markers of cancer aggressiveness, and survival difference in EBV-positive and EBV-negative prostate carcinoma. Scientific Reports, 14(1).
Available at: https://ecommons.aku.edu/pakistan_fhs_mc_bbs/1059