804 Background: Lymphovascular invasion (LVI) is a key pathological feature linked to tumor dissemination and poor outcomes in bladder cancer, yet no reliable preoperative predictor exists. Low-coverage whole-genome sequencing (lcWGS) of urinary tumor DNA (utDNA) has emerged as a noninvasive method for detecting genome-wide copy number variations (CNVs) and chromosomal instability (CIN) from urine samples, with proven value in disease diagnosis and recurrence monitoring. Typical CNV patterns in bladder cancer include recurrent gains (e.g., 1q, 8q) and losses (e.g., 5q, 9p/q), reflecting genomic instability related to tumor invasion and progression. High CIN is also recognized as an indicator of unfavorable prognosis. However, the association between specific chromosomal alterations detected in preoperative urine and LVI status remains unclear. This study aimed to evaluate the relationship between chromosomal alterations detected by urine-based lcWGS and the presence of LVI in bladder cancer. Methods: A total of 71 patients with histologically confirmed urothelial carcinoma of the bladder who underwent transurethral resection of bladder tumor (TURBT) were prospectively analyzed. Preoperative urine samples were subjected to low-coverage (~0.1×) whole-genome sequencing for CNV profiling. Z-scores were calculated for each chromosomal arm, and arms with |Z|>3 were defined as abnormal. Genome-wide CIN status was categorized as high when ≥1 arm showed |Z|>3. LVI was assessed on TURBT pathology. Associations between chromosomal alterations and LVI were tested using Fisher’s exact test, with multiple testing adjusted by the Benjamini–Hochberg (BH) procedure. Standardized mean differences (SMD) were calculated to evaluate genome-wide CNV balance between LVI groups. Results: Among 71 patients, 58 (81.7%) were classified as CIN-high and 20 (28.2%) exhibited LVI. Deletion of chromosome 5q (5q−) was detected in 17 patients, including 12 with LVI and 5 without, whereas among 54 patients without 5q−, 8 had LVI and 46 did not. Fisher’s exact test revealed a strong association between 5q− and LVI (OR = 13.8, 95% CI 3.59–43.0, p < 0.001). After BH correction across all chromosomal arms, no other arm reached statistical significance (q < 0.05), and most demonstrated |SMD| < 0.20, indicating comparable genome-wide CNV patterns between groups aside from 5q. These findings support a specific and independent link between 5q loss and the presence of LVI in bladder cancer. Conclusions: Urine-based lcWGS revealed a significant association between chromosome 5q deletion and LVI, independent of global CIN pattern differences. These findings suggest that 5q loss may serve as a potential noninvasive biomarker reflecting invasive tumor behavior in bladder cancer. Further studies are needed to elucidate the biological mechanisms underlying this association.
Xue et al. (Sun,) studied this question.