Jagged-1 induced molecular alterations in HPV associated invasive squamous cell and adenocarcinoma of the human uterine cervix

Richa Tripathi,Showket Hussain,Vishwas Sharma,Poonam Jawanjal,Gayatri Rath,Ravi Mehrotra,Kapil Bandil,Mausumi Bharadwaj

doi:10.1038/s41598-018-27699-1

Abstract

The majority of cervical cancer (CC) cases are attributable to HPV infection. Altered Notch pathway signals and HPV are believed to modify clinicopathogenesis of CC, however, the involvement of each molecular player and its mechanism is still not known. Jagged-1 (JAG1) is one of the ligands that induce Notch pathway. The involvement of JAG1 in the modulation of a disease condition is not very clear. Hence, this study aims to study the role of JAG1 in HPV-16/18 associated different histological sub-types of CC, especially ADC. 40 non-neoplastic cervical tissues, 30 precancer and 118 tumor specimens (total 188 tissue biopsies) were studied for the expression of the JAG1 protein through immunohistochemistry, immunoblotting and for HPV infection. Two folds increase of cytoplasmic (Mean ± S.E, 3.67 ± 0.33; p = 0.0001) and nuclear (3.70 ± 0.38, p = 0.0001) JAG1 expression was identified in normal (N) vs precancer and three folds cytoplasmic (4.44 ± 0.17, p = 0.0001) and nuclear (4.64 ± 0.17; p = 0.0001) in N vs. ISCC. Total 85% of ADC patients were found to be infected with HPV, which were 100% infected with HPV-16. These findings suggest the complex synergistic interplay between JAG1 and HPV in regulating clinicopathological progression of CC through its deregulation.

Highlights

This study aims to fill the research gap by measuring the expression of JAG1 in various degrees of Human Papillomavirus (HPV) linked cervical precancer, invasive squamous cell carcinomas (ISCC) and ADC patients by immunohistochemistry, in order to understand its biological role in activation of Notch signaling and to further evaluate its clinical utility in this cancer
The expression pattern (Fig. 1a–f) and total expression scores (Table 1) of JAG1 were observed in N, precancer, ISCC and ADC tissues
Two folds (Mean ± S.E, 3.67 ± 0.33; p = 0.0001) increase of cytoplasmic JAG1 expression was identified in N vs. precancer, three folds (4.44 ± 0.17; p = 0.0001) in N vs. ISCC

Summary

Objectives

This study aims to study the role of JAG1 in HPV-16/18 associated different histological sub-types of CC, especially ADC. 40 non-neoplastic cervical tissues, 30 precancer and 118 tumor specimens were studied for the expression of the JAG1 protein through immunohistochemistry, immunoblotting and for HPV infection. This study aims to study the role of JAG1 in HPV-16/18 associated different histological sub-types of CC, especially ADC. 40 non-neoplastic cervical tissues, 30 precancer and 118 tumor specimens were studied for the expression of the JAG1 protein through immunohistochemistry, immunoblotting and for HPV infection. This study aims to fill the research gap by measuring the expression of JAG1 in various degrees of HPV linked cervical precancer, ISCC and ADC patients by immunohistochemistry, in order to understand its biological role in activation of Notch signaling and to further evaluate its clinical utility in this cancer

Methods

Results

Conclusion