PIK3R1 acts as a prominent biomarker for tumor immune microenvironment modulation in intravenous leiomyomatosis
In current clinical practice, intravenous leiomyomatosis (IVL) can be surgically resected using either one-step or two-step approach. However, several challenges persist, including a high rate of postoperative recurrence, the difficulty in achieving complete resection in complex cases, and the inability to timely identify a substantial number of early-stage IVL cases. The mainstream theory regarding the pathogenesis and development mechanism of IVL is that it originates from uterine leiomyomas, yet the specific molecular mechanisms underlying this process remain to be elucidated. In this study, high-throughput transcriptome sequencing and molecular detection methods such as immunohistochemistry were employed to analyze the molecular expression differences at the transcriptome and immune microenvironment levels between 5 cases of IVL and paired uterine leiomyomas. These findings were subsequently validated in a cohort consisting of 45 IVL cases. The cross-enrichment analysis of differentially expressed genes (DEGs) at the transcriptome and immune level in paired samples yielded significant results. Notably, the up-regulated gene PIK3R1 and the down-regulated gene BMP4 emerged as two of the most critical representatives. Further investigation into the function of the PIK3R1 gene in IVL and its relationship with the immune microenvironment revealed that this gene was highly expressed in IVL and positively correlated with the abundance of plasma cells, while negatively correlated with follicular helper T cells and resting dendritic cells. The overall immune microenvironment of IVL was inactive, leading to tumor cells being less likely to be recognized and eliminated by immune cells. This study has conducted an in-depth analysis of the molecular expression, immune microenvironment characteristics, and related mechanisms of IVL. Further studies on larger cohort are warranted to demonstrate the potential value of inhibiting PIK3R1 as the adjuvant medicine for IVL therapy.