BRAF V600E-mutant colorectal cancer (CRC) is a rare subtype of colorectal cancer with poor prognosis. Compelling evidence indicates that the heparanase (HPSE) gene has multiple functions in cancer, however, its role in BRAF V600E-mutant CRC remains elusive. Differentially expressed genes between BRAF V600E-mutant and wild-type patients were explored by analyzing public data from The Cancer Genome Atlas and the Gene Expression Omnibus. Clinical samples of 172 patients with BRAF V600E-mutant CRC diagnosed at Zhongshan Hospital Fudan University were collected. Overall survival was analyzed using Kaplan–Meier curves and Cox regression models. Cell models and xenografts were utilized to investigate the effect of HPSE on tumor proliferation. HPSE was significantly highly expressed in the BRAF V600E-mutant group. High HPSE expression level was independently associated with inferior survival in the BRAF V600E-mutant cohort. HPSE knockdown impeded tumor proliferation of BRAF V600E-mutant CRC cells in vitro and in vivo. Mechanistically, HPSE silencing arrested cell cycle in G0/G1 phase by downregulating Cyclin E2 expression via the AKT/p27Kip1 pathway. These findings support a role for HPSE in promoting BRAF V600E-mutant CRC progression, which suggests it holds great promise as a prognostic biomarker and a potential therapeutic target for the aggressive CRC subtype.

BRAF V600E突变型结直肠癌（CRC）是一种罕见的结直肠癌亚型，预后不良。令人信服的证据表明乙酰肝素酶 ( HPSE ) 基因在癌症中具有多种功能，然而，它在BRAF V600E 突变型 CRC 中的作用仍然难以捉摸。通过分析来自 The Cancer Genome Atlas 和 Gene Expression Omnibus 的公共数据，探索了BRAF V600E 突变体和野生型患者之间的差异表达基因。收集了复旦大学中山医院确诊的 172 例BRAF V600E 突变型 CRC 患者的临床样本。使用 Kaplan-Meier 曲线和 Cox 回归模型分析总生存期。细胞模型和异种移植物用于研究HPSE对肿瘤增殖的影响。HPSE在BRAF V600E 突变组中显着高表达。在BRAF V600E 突变组中，高HPSE表达水平与较差的生存率独立相关。HPSE敲低在体外和体内阻碍了BRAF V600E 突变 CRC 细胞的肿瘤增殖。从机制上讲，HPSE沉默通过 AKT/p27Kip1 通路下调 Cyclin E2 表达，使细胞周期停滞在 G0/G1 期。这些发现支持HPSE在促进BRAF中的作用V600E 突变 CRC 进展，这表明它作为预后生物标志物和侵袭性 CRC 亚型的潜在治疗靶标具有很大的前景。