ROMO1 as a Diagnostic Biomarker in Cervical Neoplasia: Evidence from Normal, Pre-Invasive, and Invasive Lesions

Area of Science:

• Oncology
• Biomarker Discovery
• Gynecologic Pathology

Background:

• Cervical cancer (CC) is a major global health concern, particularly in developing nations, with persistent high-risk human papillomavirus (HPV) infection as the primary cause.
• Current biomarkers like p16 and Ki-67 have limitations in distinguishing progressive from transient HPV infections, necessitating novel biomarkers for improved accuracy.
• ROMO1, a marker associated with high-ROS, high-risk tumors, has not been studied in the context of cervical neoplasia, despite links between oxidative stress and HPV-driven carcinogenesis.

Purpose of the Study:

• To investigate the expression pattern of ROMO1 throughout the development of cervical squamous neoplastic lesions, from normal epithelium to invasive carcinoma.
• To determine if ROMO1 expression correlates with the severity and clinicopathologic features of cervical intraepithelial neoplasia (CIN) and cervical cancer (CC).
• To evaluate ROMO1 as a potential auxiliary biomarker for the early detection of cervical cancer and high-grade precancerous lesions.

Main Methods:

• Immunohistochemical analysis of ROMO1 expression was performed on cervical tissue samples.
• Samples included healthy cervix (n=30), cervical intraepithelial neoplasia (CIN) (n=41), and invasive cervical carcinoma (n=205).
• ROMO1 expression in invasive carcinoma was quantified using an H-score, and results were analyzed for associations with various clinicopathologic variables.

Main Results:

• ROMO1 expression was negligible in normal cervical epithelium but showed 100% expression in the suprabasal layers of CIN lesions.
• In invasive cervical carcinomas, ROMO1 expression was heterogeneous, highest in stage I tumors and declining in more advanced stages.
• ROMO1 expression showed a significant association with histologic subtype (SCC vs. AC/ASC) and tumor stage (pT1b1 vs. pT2a), but not with FIGO stage, grade, lymphovascular invasion, nodal status, or patient age.

Conclusions:

• ROMO1 exhibits a distinct expression pattern across the cervical neoplasia spectrum: negligible in normal tissue, significantly elevated in CIN, and attenuated in invasive tumors with a peak in early stages.
• The overexpression of ROMO1 in early lesions supports the hypothesis that oxidative stress plays a role in the initial stages of cervical malignant transformation.
• ROMO1 holds promise as a valuable auxiliary biomarker for detecting high-grade precancerous lesions and early-stage cervical cancer.