BACKGROUND As a novel endogenous anti-angiogenic molecule, vasohibin 1(VASH1) is not only expressed in tumor stroma, but also in tumor tissue. Moreover, studies have shown that VASH1 may be a prognostic marker in colo...BACKGROUND As a novel endogenous anti-angiogenic molecule, vasohibin 1(VASH1) is not only expressed in tumor stroma, but also in tumor tissue. Moreover, studies have shown that VASH1 may be a prognostic marker in colorectal cancer(CRC). Knockdown of VASH1 enhanced transforming growth factor-β1(TGF-β1)/Smad3 pathway activity and type Ⅰ/Ⅲ collagen production. Our previous findings suggest that ELL-associated factor 2(EAF2) may play a tumor suppressor and protective role in the development and progression of CRC by regulating signal transducer and activator of transcription 3(STAT3)/TGF-β1 signaling pathway. However, the functional role and mechanism of VASH1-mediated TGF-β1 related pathway in CRC has not been elucidated.AIM To investigate the expression of VASH1 in CRC and its correlation with the expression of EAF2. Furthermore, we studied the functional role and mechanism of VASH1 involved in the regulation and protection of EAF2 in CRC cells in vitro.METHODS We collected colorectal adenocarcinoma and corresponding adjacent tissues to investigate the clinical expression of EAF2 protein and VASH1 protein in patients with advanced CRC. Following, we investigated the effect and mechanism of EAF2 and VASH1 on the invasion, migration and angiogenesis of CRC cells in vitro using plasmid transfection.RESULTS Our findings indicated that EAF2 was down-regulated and VASH1 was upregulated in advanced CRC tissue compared to normal colorectal tissue. KaplanMeier survival analysis showed that the higher EAF2 Level group and the lower VASH1 Level group had a higher survival rate. Overexpression of EAF2 might inhibit the activity of STAT3/TGF-β1 pathway by up-regulating the expression of VASH1, and then weaken the invasion, migration and angiogenesis of CRC cells.CONCLUSION This study suggests that EAF2 and VASH1 may serve as new diagnostic and prognostic markers for CRC, and provide a clinical basis for exploring new biomarkers for CRC. This study complements the mechanism of EAF2 in CRC cells, enriches the role and mechanism of CRC cellderived VASH1, and provides a new possible subtype of CRC as a therapeutic target of STAT3/TGF-β1 pathway.展开更多
目的:探讨浆液性卵巢癌中血管生成抑制蛋白-1(vasohibin-1)、结肠癌转移相关蛋白1(metastasis-associated in colon cancer-1,MACC1)和抗癌1号蛋白(KAI1)表达之间的关系及其临床意义。方法:收集124例卵巢浆液性癌(卵巢浆液性癌组)和30...目的:探讨浆液性卵巢癌中血管生成抑制蛋白-1(vasohibin-1)、结肠癌转移相关蛋白1(metastasis-associated in colon cancer-1,MACC1)和抗癌1号蛋白(KAI1)表达之间的关系及其临床意义。方法:收集124例卵巢浆液性癌(卵巢浆液性癌组)和30例卵巢浆液性囊腺瘤(卵巢浆液性囊腺瘤组)术后组织标本,采用免疫组织化学ElivisionTM法检测所有肿瘤组织中vasohibin-1,MACC1和KAI1蛋白的表达情况。结果:卵巢浆液性癌组vasohibin-1和MACC1蛋白的阳性表达率分别为48.4%和58.1%,均高于卵巢浆液性囊腺瘤组(分别为10.0%和13.3%);而卵巢浆液性癌组KAI1蛋白阳性表达率为33.9%,低于浆液性囊腺瘤组(86.7%),差异均有统计学意义(均P<0.05);3种蛋白的表达与浆液性卵巢癌的病理组织学分级、国际妇产科联盟(Federation International of Gynecology and Obstetrics,FIGO)分期以及盆腔淋巴结转移有关(均P<0.05);KAI1蛋白的表达与vasohibin-1和MACC1的表达呈负相关(r值分别为–0.500和–0.600,均P<0.01),同时,vasohibin-1与MACC1蛋白的表达呈正相关(r=0.518,P<0.01)。Kaplan-Meier生存分析表明:vasohibin-1和MACC1的过表达以及KAI1的低表达均与患者的生存率有关,vasohibin-1和MACC1表达阳性及KAI1表达阴性的患者生存率明显低于vasohibin-1和MACC1表达阴性及KAI1表达阳性的患者(均P<0.05)。多因素分析表明:FIGO分期、vasohibin-1和KAI1蛋白的表达是影响浆液性卵巢癌根治术后患者预后的独立因素(RR值分别为2.185,3.893,0.413;95% CI分别为1.263~3.779,2.190~6.921,0.251~0.681;均P<0.05)。结论:浆液性卵巢癌组织中vasohibin-1和MACC1的表达上调以及KAI1的表达下调与肿瘤的分化程度、临床分期、转移和预后等因素相关,这些指标的联合检测可作为判断浆液性卵巢癌患者肿瘤演进及生存预后的重要指标。展开更多
基金the Natural Science Foundation of Liaoning Province,No.2023-MS-149.
文摘BACKGROUND As a novel endogenous anti-angiogenic molecule, vasohibin 1(VASH1) is not only expressed in tumor stroma, but also in tumor tissue. Moreover, studies have shown that VASH1 may be a prognostic marker in colorectal cancer(CRC). Knockdown of VASH1 enhanced transforming growth factor-β1(TGF-β1)/Smad3 pathway activity and type Ⅰ/Ⅲ collagen production. Our previous findings suggest that ELL-associated factor 2(EAF2) may play a tumor suppressor and protective role in the development and progression of CRC by regulating signal transducer and activator of transcription 3(STAT3)/TGF-β1 signaling pathway. However, the functional role and mechanism of VASH1-mediated TGF-β1 related pathway in CRC has not been elucidated.AIM To investigate the expression of VASH1 in CRC and its correlation with the expression of EAF2. Furthermore, we studied the functional role and mechanism of VASH1 involved in the regulation and protection of EAF2 in CRC cells in vitro.METHODS We collected colorectal adenocarcinoma and corresponding adjacent tissues to investigate the clinical expression of EAF2 protein and VASH1 protein in patients with advanced CRC. Following, we investigated the effect and mechanism of EAF2 and VASH1 on the invasion, migration and angiogenesis of CRC cells in vitro using plasmid transfection.RESULTS Our findings indicated that EAF2 was down-regulated and VASH1 was upregulated in advanced CRC tissue compared to normal colorectal tissue. KaplanMeier survival analysis showed that the higher EAF2 Level group and the lower VASH1 Level group had a higher survival rate. Overexpression of EAF2 might inhibit the activity of STAT3/TGF-β1 pathway by up-regulating the expression of VASH1, and then weaken the invasion, migration and angiogenesis of CRC cells.CONCLUSION This study suggests that EAF2 and VASH1 may serve as new diagnostic and prognostic markers for CRC, and provide a clinical basis for exploring new biomarkers for CRC. This study complements the mechanism of EAF2 in CRC cells, enriches the role and mechanism of CRC cellderived VASH1, and provides a new possible subtype of CRC as a therapeutic target of STAT3/TGF-β1 pathway.
文摘目的:探讨浆液性卵巢癌中血管生成抑制蛋白-1(vasohibin-1)、结肠癌转移相关蛋白1(metastasis-associated in colon cancer-1,MACC1)和抗癌1号蛋白(KAI1)表达之间的关系及其临床意义。方法:收集124例卵巢浆液性癌(卵巢浆液性癌组)和30例卵巢浆液性囊腺瘤(卵巢浆液性囊腺瘤组)术后组织标本,采用免疫组织化学ElivisionTM法检测所有肿瘤组织中vasohibin-1,MACC1和KAI1蛋白的表达情况。结果:卵巢浆液性癌组vasohibin-1和MACC1蛋白的阳性表达率分别为48.4%和58.1%,均高于卵巢浆液性囊腺瘤组(分别为10.0%和13.3%);而卵巢浆液性癌组KAI1蛋白阳性表达率为33.9%,低于浆液性囊腺瘤组(86.7%),差异均有统计学意义(均P<0.05);3种蛋白的表达与浆液性卵巢癌的病理组织学分级、国际妇产科联盟(Federation International of Gynecology and Obstetrics,FIGO)分期以及盆腔淋巴结转移有关(均P<0.05);KAI1蛋白的表达与vasohibin-1和MACC1的表达呈负相关(r值分别为–0.500和–0.600,均P<0.01),同时,vasohibin-1与MACC1蛋白的表达呈正相关(r=0.518,P<0.01)。Kaplan-Meier生存分析表明:vasohibin-1和MACC1的过表达以及KAI1的低表达均与患者的生存率有关,vasohibin-1和MACC1表达阳性及KAI1表达阴性的患者生存率明显低于vasohibin-1和MACC1表达阴性及KAI1表达阳性的患者(均P<0.05)。多因素分析表明:FIGO分期、vasohibin-1和KAI1蛋白的表达是影响浆液性卵巢癌根治术后患者预后的独立因素(RR值分别为2.185,3.893,0.413;95% CI分别为1.263~3.779,2.190~6.921,0.251~0.681;均P<0.05)。结论:浆液性卵巢癌组织中vasohibin-1和MACC1的表达上调以及KAI1的表达下调与肿瘤的分化程度、临床分期、转移和预后等因素相关,这些指标的联合检测可作为判断浆液性卵巢癌患者肿瘤演进及生存预后的重要指标。
