JAM3 as a Prognostic Biomarker in Muscle-Invasive Urothelial Carcinoma: Correlation With Therapeutic Response and Survival Outcomes

Bladder cancer(BC) is the 10th most common cancer globally, with a higher incidence in males than females, being the 6th most common cancer in men with high mortality, causing a societal burden worldwide.

Known risk factors include age, gender, cigarettes, genetic factors, and other environmental influences .

BC can be classified into non-muscle-invasive BC (NMIBC) and muscle-invasive BC (MIBC) . MIBC exhibits a more aggressive nature, correlates with a higher level of T-stage, and has more significant genetic heterogeneity .

Despite comprehensive treatment regimens comprising neoadjuvant chemotherapy, radical cystectomy (RC) and adjuvant immunotherapies, a significant proportion of MIBC patients continue to progress to more advanced stages with limited clinical indicators.

Unfortunately, the mechanisms underlying BC initiation, proliferation, and progression remain largely unknown.

The occurrence of genetic alterations is believed to be closely linked to BC tumorigenesis. Therefore, investigating the genetic alterations might offer opportunities to further understand biological changes in BC .

A key mechanism underlying tumor progression and metastasis is the epithelial-mesenchymal transition (EMT), which is associated with increased invasiveness, chemoresistance, and immune evasion.

EMT is characterized by the downregulation of epithelial markers such as E-cadherin (CDH1) and the upregulation of mesenchymal markers like N-cadherin (CDH2), vimentin, Snail, and ZEB proteins .

Emerging evidence suggests that junctional adhesion molecule 3 (JAM3) plays a role in EMT and cancer progression, with documented involvement in gastric cancer.

However, its significance in MIBC remains poorly understood. Investigating JAM3 expression in MIBC may provide novel prognostic insights and help refine patient stratification for NAC and immunotherapy.

Aim:

This study aims to analyze JAM3 expression in transurethral biopsies from MIUC patients and correlate it with:

• Tumor aggressiveness (grading, staging, and histological features).
• Response to neoadjuvant chemotherapy .
• Patient survival and disease progression.

This study will provide a better understanding of JAM3's role in EMT and MIUC progression, offering potential biomarker-driven insights for treatment stratification.

If JAM3 is validated as a prognostic factor, it could guide personalized therapeutic approaches and optimizing NAC outcomes.