Abstract：
OBJECTIVE: The low expression of somatostatin receptor (SSTR) subtypes in somatotropinoma is associated with a poor response to somatostatin analogs (SSAs). However, the correlation between SSTRs and tumor invasion has not yet been clarified. Therefore, the authors aimed to investigate the relationship between SSTRs and tumor invasion, as well as the correlation between tumor invasiveness and pharmacological response to SSAs.
METHODS: A total of 102 patients with acromegaly who underwent surgery between December 2016 and December 2021 at the largest pituitary tumor surgery center in southern China were included in this retrospective study. Patients were divided into the noninvasive tumor group (Knosp grades 0-2 and Hardy-Wilson grade I or II) and invasive group (either Knosp grade 3 or 4 or Hardy-Wilson grade III or IV). The positive response to SSAs was defined by the following criteria after at least 3 months of SSA treatment: 1) ≥ 50% reduction or age- and sex-adjusted normal range of insulin-like growth factor-1 (IGF-1) level; 2) ≥ 80% reduction in or normal range of growth hormone (GH) level; or 3) > 20% reduction in tumor volume. The reference for the normal range of age- and sex-adjusted serum IGF-1 levels was derived from a survey of 2791 healthy adults (1339 males and 1452 females) in China. Demographics and clinical characteristics including tumor size, biochemical assessment, expression levels of SSTRs, and response to preoperative SSAs were compared between the invasive group and noninvasive group. Receiver operating characteristic (ROC) curve analysis was performed to assess the association between SSTR2 and tumor invasion.
RESULTS: Compared with the noninvasive group, the invasive group presented with a larger tumor size (9.99 ± 10.41 cm3 vs 3.50 ± 4.02 cm3, p < 0.001), relatively lower SSTR2 expression (p < 0.001), and poorer response to SSAs (36.4% vs 91.7%, p < 0.001). In addition, there was a significant negative correlation between SSTR2 mRNA level and tumor size (r = -0.214, p = 0.031). However, there were no statistically significant differences in the expression of SSTR1, SSTR3, and SSTR5 between the groups. ROC analysis revealed that the low SSTR2 mRNA level was closely associated with tumor invasion (area under the curve 0.805, p < 0.0001).
CONCLUSIONS: Tumor invasion is negatively correlated with SSTR2 level but is not associated with other SSTR subtypes. Patients with invasive tumors have a poorer response to SSA therapy, which may be due to the low level of SSTR2 expression. Therefore, SSTR2 could be considered as a routine investigative marker for aiding management of postoperative residual tumors.
METHODS: A total of 102 patients with acromegaly who underwent surgery between December 2016 and December 2021 at the largest pituitary tumor surgery center in southern China were included in this retrospective study. Patients were divided into the noninvasive tumor group (Knosp grades 0-2 and Hardy-Wilson grade I or II) and invasive group (either Knosp grade 3 or 4 or Hardy-Wilson grade III or IV). The positive response to SSAs was defined by the following criteria after at least 3 months of SSA treatment: 1) ≥ 50% reduction or age- and sex-adjusted normal range of insulin-like growth factor-1 (IGF-1) level; 2) ≥ 80% reduction in or normal range of growth hormone (GH) level; or 3) > 20% reduction in tumor volume. The reference for the normal range of age- and sex-adjusted serum IGF-1 levels was derived from a survey of 2791 healthy adults (1339 males and 1452 females) in China. Demographics and clinical characteristics including tumor size, biochemical assessment, expression levels of SSTRs, and response to preoperative SSAs were compared between the invasive group and noninvasive group. Receiver operating characteristic (ROC) curve analysis was performed to assess the association between SSTR2 and tumor invasion.
RESULTS: Compared with the noninvasive group, the invasive group presented with a larger tumor size (9.99 ± 10.41 cm3 vs 3.50 ± 4.02 cm3, p < 0.001), relatively lower SSTR2 expression (p < 0.001), and poorer response to SSAs (36.4% vs 91.7%, p < 0.001). In addition, there was a significant negative correlation between SSTR2 mRNA level and tumor size (r = -0.214, p = 0.031). However, there were no statistically significant differences in the expression of SSTR1, SSTR3, and SSTR5 between the groups. ROC analysis revealed that the low SSTR2 mRNA level was closely associated with tumor invasion (area under the curve 0.805, p < 0.0001).
CONCLUSIONS: Tumor invasion is negatively correlated with SSTR2 level but is not associated with other SSTR subtypes. Patients with invasive tumors have a poorer response to SSA therapy, which may be due to the low level of SSTR2 expression. Therefore, SSTR2 could be considered as a routine investigative marker for aiding management of postoperative residual tumors.
摘要：
目的：促生长素瘤中生长抑素受体（SSTR）亚型的低表达与对生长抑素类似物（SSAs）的反应不良有关。然而,SSTRs与肿瘤侵袭之间的相关性尚未明确。因此,作者旨在研究SSTRs与肿瘤侵袭之间的关系，以及肿瘤侵袭性与SSAs药理反应之间的相关性。
方法：这项回顾性研究纳入了在2016年12月至2021年12月期间在中国南方最大的垂体瘤手术中心接受手术的102例肢端肥大症患者。患者分为非侵袭性肿瘤组（Knosp等级0-2和Hardy-Wilson等级I或II）和侵袭性肿瘤组（Knosp等级3或4或Hardy-Wilson等级III或IV）。SSA治疗至少3个月后，对SSA的阳性反应由以下标准定义：1）胰岛素样生长因子-1（IGF-1）水平降低≥50％或年龄和性别调整的正常范围；2）生长激素（GH）水平降低≥80％或正常范围；或3）肿瘤体积减少>20％。年龄和性别调整后的血清IGF-1水平正常范围的参考来自对中国2791名健康成年人（男性1339名，女性1452名）的调查。人口统计学和临床特征，包括肿瘤大小，生化评估，SSTRs的表达水平，比较侵入组和非侵入组之间对术前SSA的反应。进行受试者工作特征（ROC）曲线分析以评估SSTR2与肿瘤侵袭之间的关联。
结果：与无创性组相比，侵袭组肿瘤体积较大（9.99±10.41cm3vs3.50±4.02cm3，p<0.001），SSTR2表达相对较低（p<0.001），对SSA的反应较差(36.4%对91.7%，p<0.001)。此外,SSTR2mRNA水平与肿瘤大小呈显著负相关(r=-0.214,p=0.031)。然而,各组间SSTR1、SSTR3和SSTR5的表达差异无统计学意义。ROC分析显示低SSTR2mRNA水平与肿瘤侵袭密切相关(曲线下面积0.805,p<0.0001)。
结论：肿瘤侵袭与SSTR2水平呈负相关，但与其他SSTR亚型无关。浸润性肿瘤患者对SSA治疗的反应较差，这可能是由于SSTR2表达水平低。因此,SSTR2可以被认为是辅助治疗术后残留肿瘤的常规研究标记。
方法：这项回顾性研究纳入了在2016年12月至2021年12月期间在中国南方最大的垂体瘤手术中心接受手术的102例肢端肥大症患者。患者分为非侵袭性肿瘤组（Knosp等级0-2和Hardy-Wilson等级I或II）和侵袭性肿瘤组（Knosp等级3或4或Hardy-Wilson等级III或IV）。SSA治疗至少3个月后，对SSA的阳性反应由以下标准定义：1）胰岛素样生长因子-1（IGF-1）水平降低≥50％或年龄和性别调整的正常范围；2）生长激素（GH）水平降低≥80％或正常范围；或3）肿瘤体积减少>20％。年龄和性别调整后的血清IGF-1水平正常范围的参考来自对中国2791名健康成年人（男性1339名，女性1452名）的调查。人口统计学和临床特征，包括肿瘤大小，生化评估，SSTRs的表达水平，比较侵入组和非侵入组之间对术前SSA的反应。进行受试者工作特征（ROC）曲线分析以评估SSTR2与肿瘤侵袭之间的关联。
结果：与无创性组相比，侵袭组肿瘤体积较大（9.99±10.41cm3vs3.50±4.02cm3，p<0.001），SSTR2表达相对较低（p<0.001），对SSA的反应较差(36.4%对91.7%，p<0.001)。此外,SSTR2mRNA水平与肿瘤大小呈显著负相关(r=-0.214,p=0.031)。然而,各组间SSTR1、SSTR3和SSTR5的表达差异无统计学意义。ROC分析显示低SSTR2mRNA水平与肿瘤侵袭密切相关(曲线下面积0.805,p<0.0001)。
结论：肿瘤侵袭与SSTR2水平呈负相关，但与其他SSTR亚型无关。浸润性肿瘤患者对SSA治疗的反应较差，这可能是由于SSTR2表达水平低。因此,SSTR2可以被认为是辅助治疗术后残留肿瘤的常规研究标记。
