Nakamichi Naosuke, Shiozaki Atsushi, Kosuga Toshiyuki, Shimizu Hiroki, Kudou Michihiro, Kiuchi Jun, Nanishi Kenji, Arita Tomohiro, Konishi Hirotaka, Komatsu Shuhei, Kuriu Yoshiaki, Kubota Takeshi, Fujiwara Hitoshi, Morinaga Yukiko, Konishi Eiichi, Otsuji Eigo
Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Surgical Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Ann Surg Oncol. 2025 Aug 19. doi: 10.1245/s10434-025-18083-1.
Transient receptor potential vanilloid 2 (TRPV2) is a calcium channel involved in signaling pathways that control cell proliferation, the cell cycle, and apoptosis. The relationship between TRPV2 expression and prognosis has been reported in cancers of various organs. However, the functions and clinical significance of TRPV2 in colon cancer (CC) remain unclear. This study aimed to investigate the role of TRPV2 in CC.
After small interfering RNA-induced TRPV2 knockdown in CC cells, we examined the effects on cell proliferation, cell cycle, apoptosis, and wound-healing. Gene expression profiles of CC cells were examined using microarray analysis. Immunohistochemistry of TRPV2 expression was performed on samples from 200 patients who underwent radical colectomy. The patients were divided into two groups according to TRPV2 expression, and their clinicopathologic background and prognosis were analyzed.
The study showed that TRPV2-depleted CC cells reduced cell proliferation and migration, together with the induction of apoptosis. Based on the cell cycle assay, the transition from the G1 to the S phase was suppressed in the cell cycle. The microarray analysis showed that TRPV2 was involved in PI3K/AKT-, ERK/MAPK-, and role of tissue factor in cancer-signaling pathways. Immunohistochemical analysis showed that high TRPV2 expression was an independent poor prognostic factor (p = 0.016; hazard ratio, 2.045).
The study findings suggested that TRPV2 controls the proliferation, apoptosis, and migration of CC cells. Furthermore, the study identified high TRPV2 expression as a poor prognostic factor for patients with CC.
瞬时受体电位香草酸亚型2(TRPV2)是一种钙通道,参与控制细胞增殖、细胞周期和细胞凋亡的信号通路。TRPV2表达与多种器官癌症预后的关系已有报道。然而,TRPV2在结肠癌(CC)中的功能和临床意义仍不清楚。本研究旨在探讨TRPV2在CC中的作用。
在CC细胞中通过小干扰RNA诱导TRPV2基因敲低后,我们检测了其对细胞增殖、细胞周期、细胞凋亡和伤口愈合的影响。使用微阵列分析检测CC细胞的基因表达谱。对200例行根治性结肠切除术患者的样本进行TRPV2表达的免疫组织化学检测。根据TRPV2表达将患者分为两组,并分析其临床病理背景和预后。
研究表明,TRPV2缺失的CC细胞可减少细胞增殖和迁移,并诱导细胞凋亡。基于细胞周期分析,细胞周期中从G1期到S期的转变受到抑制。微阵列分析表明,TRPV2参与PI3K/AKT、ERK/MAPK以及组织因子在癌症信号通路中的作用。免疫组织化学分析表明,TRPV2高表达是一个独立的不良预后因素(p = 0.016;风险比,2.045)。
研究结果表明,TRPV2控制CC细胞的增殖、凋亡和迁移。此外,该研究确定TRPV2高表达是CC患者的不良预后因素。