Expression and Clinical Significance of ROR1 in Different Histologic Types of Invasive Lung Adenocarcinoma
-
摘要:
目的 研究受体酪氨酸激酶样孤儿受体1（receptor tyrosine kinase-like orphan rectetpor 1，ROR1）在不同组织学分级的浸润性肺腺癌中的表达情况，分析其与肺腺癌病理组织学分级的关系；探讨其是否可作为浸润性肺腺癌诊断评估的潜在指标。 方法 收集浸润性肺腺癌石蜡包埋组织标本290例，行HE染色切片后进行组织学分级，通过免疫组化染色，使用半定量法判读ROR1表达水平，统计分析ROR1表达与浸润性肺腺癌分级的关系。 结果 ROR1高表达于低分化的浸润性肺腺癌（P < 0.001）；低分化组的浸润性肺腺癌中Ki-67指数明显高于高、中分化组（P < 0.001）；Ki-67指数在ROR1高表达组高于低表达组（P < 0.01）。 结论 ROR1在不同分级的肺腺癌中表达水平存在明显差异，其表达水平与浸润性肺腺癌的分化程度及恶性程度密切相关，这使得它有可能成为新的肺腺癌诊断生物标志物并辅助肺腺癌的临床特征和预后的评估，为患者制定个性化治疗策略提供科学依据。 Abstract:Objective To investigate the expression of receptor tyrosine kinase-like orphan rectetpor 1 （ROR1） in invasive lung adenocarcinoma with different histological grades, and to analyze its relationship with histopathological grade of lung adenocarcinoma so as to explore whether it can be used as a potential indicator for the diagnostic evaluation of invasive lung adenocarcinoma. Methods A total of 290 paraffin-embedded tissue specimens of invasive lung adenocarcinoma were collected, and the relationship between ROR1 expression and invasive lung adenocarcinoma grade was statistically analyzed by HE staining sections. Results ROR1 was significantly highly expressed in the poorly differentiated invasive lung adenocarcinoma （P < 0.001）, the Ki-67 index in the low-differentiated group was significantly higher than that in the high-differentiation and medium-differentiated groups（P < 0.001）, and the Ki-67 index was higher in the high-expression group than in the low-expression group （P < 0.01）. Conclusion There are significant differences in the expression levels of ROR1 in different grades of lung adenocarcinoma, and its expression level is closely related to the degree of differentiation and malignancy of invasive lung adenocarcinoma, which makes it possible to become a new biomarker for the diagnosis of lung adenocarcinoma and assist in the evaluation of clinical features and prognosis of lung adenocarcinoma, and provide a scientific basis to formulate personalized treatment strategies for patients. -
Key words:
- Lung adenocarcinoma /
- ROR1 /
- Ki-67 /
- Pathological grading /
- Immunohistochemistry
-
图 1 浸润性肺腺癌组织学分级（HE×200）
A：高分化；B：中分化；C：低分化。
Figure 1. Histological grading of invasive lung adenocarcinoma （HE×200）
图 2 ROR1在不同组织学分级肺腺癌中的强度（IHC×200）
A：弱阳性；B：中阳性；C：强阳性。
Figure 2. The intensity of ROR1 in different histologically graded lung adenocarcinoma （IHC×200）
表 1 ROR1在不同分级肺腺癌中的表达[n（%）]
Table 1. Expression of ROR1 in different grades of lung adenocarcinoma[n（%）]
肺腺癌病理分级 n ROR1 χ2 P 高表达 低表达 高分化 49 15（30.61） 34（69.39）
61.534
<0.001*中分化 180 139（77.22） 41（22.88） 低分化 61 58（95.08） 3（4.92） *P < 0.05。 
下载: 导出CSV
表 2 肺腺癌不同组织学分级与Ki-67指数相关性
Table 2. Ki-67 index of lung adenocarcinoma with different histological grades
肺腺癌病理分级 n Ki-67指数 r P 高分化 49 4.78 −0.750 <0.001* 中分化 180 11.68 低分化 61 38.85 *P < 0.05。
下载: 导出CSV
表 3 ROR1表达程度与Ki-67指数的相关性
Table 3. Relationship between ROR1 expression degree and Ki-67 index
ROR1 n Ki-67指数 r P 高表达 212 19.88 −0.527 0.001* 低表达 78 6.32 *P < 0.05。
下载: 导出CSV
-
[1] 金美华,唐娟,秦家丽,等. 2002—2020年间的肺癌流行病学分析[J]. 华夏医学,2021,34(6):34-38. [2] 司华,闫灿,曾宪焕. TN-C和Ki-67的表达与非小细胞肺癌临床病理特征的相关性[J]. 实用癌症杂志,2021,36(3):360-363. [3] Chen P,Liu Y,Wen Y,et al. Non-small cell lung cancer in China[J]. Cancer Commun (Lond),2022,42(10):937-970. doi: 10.1002/cac2.12359 [4] 张仁锋,张岩,温丰标,等. 6,058例肺癌患者病理类型和临床流行病学特征的分析[J]. 中国肺癌杂志,2016,19(3):129-135. [5] Siegel R L,Miller K D,Jemal A. Cancer statistics,2017[J]. CA Cancer J Clin,2017,67(1):7-30. doi: 10.3322/caac.21387 [6] Sung H J,Cho J Y. Biomarkers for the lung cancer diagnosis and their advances in proteomics[J]. BMB Rep,2008,41(9):615-625. doi: 10.5483/BMBRep.2008.41.9.615 [7] Borcherding N,Kusner D,Liu G H,et al. ROR1,an embryonic protein with an emerging role in cancer biology[J]. Protein Cell,2014,5(7):496-502. doi: 10.1007/s13238-014-0059-7 [8] Cetin M,Odabas G,Douglas L R,et al. ROR1 expression and its functional significance in hepatocellular carcinoma cells[J]. Cells,2019,8(3):210. doi: 10.3390/cells8030210 [9] Nomi M,Oishi I,Kani S,et al. Loss of mRor1 enhances the heart and skeletal abnormalities in mRor2-deficient mice: Redundant and pleiotropic functions of mRor1 and mRor2 receptor tyrosine kinases[J]. Mol Cell Biol,2001,21(24):8329-8335. doi: 10.1128/MCB.21.24.8329-8335.2001 [10] Ho H Y,Susman M W,Bikoff J B,et al. Wnt5a-Ror-Dishevelled signaling constitutes a core developmental pathway that controls tissue morphogenesis[J]. Proc Natl Acad Sci USA,2012,109(11):4044-4051. doi: 10.1073/pnas.1200421109 [11] Hudecek M,Lupo-Stanghellini M T,Kosasih P L,et al. Receptor affinity and extracellular domain modifications affect tumor recognition by ROR1-specific chimeric antigen receptor T cells[J]. Clin Cancer Res,2013,19(12):3153-3164. doi: 10.1158/1078-0432.CCR-13-0330 [12] Ma X,Zhang Y,Liu B,et al. Backbone and side-chain chemical shift assignments of the kringle domain of human receptor tyrosine kinase-like orphan receptor 1 (ROR1)[J]. Biomol NMR Assign,2018,12(1):145-148. doi: 10.1007/s12104-017-9797-9 [13] 赵鑫,丁琳,陈煜选,等. ROR蛋白在癌症中的研究进展[J]. 中国细胞生物学学报,2022,44(12):2354-2365. [14] Cui B,Zhang S,Chen L,et al. Targeting ROR1 inhibits epithelial-mesenchymal transition and metastasis[J]. Cancer Res,2013,73(12):3649-3660. doi: 10.1158/0008-5472.CAN-12-3832 [15] Qi J,Li X,Peng H,et al. Potent and selective antitumor activity of a T cell-engaging bispecific antibody targeting a membrane-proximal epitope of ROR1[J]. Proc Natl Acad Sci USA,2018,115(24):E5467-E5476. [16] Zhang S,Chen L,Cui B,et al. ROR1 is expressed in human breast cancer and associated with enhanced tumor-cell growth[J]. PLoS One,2012,7(3):e31127. doi: 10.1371/journal.pone.0031127 [17] 陈梦云,张翠翠,轩菡,等. Ki67在肿瘤中的表达及其临床指导意义[J]. 现代生物医学进展,2015,15(16):3193-3196. [18] 许丽莉,郭人花. Ki67表达及EGFR突变对Ⅰ期肺腺癌患者术后复发转移风险的相关分析[J]. 中国肺癌杂志,2022,25(12):852-861. [19] 李媛,谢惠康,武春燕. WHO胸部肿瘤分类(第5版)中肺肿瘤部分解读[J]. 中国癌症杂志,2021,31(7):574-580. [20] Zhang S,Cui B,Lai H,et al. Ovarian cancer stem cells express ROR1,which can be targeted for anti-cancer-stem-cell therapy[J]. Proc Natl Acad Sci U S A,2014,111(48):17266-17271. doi: 10.1073/pnas.1419599111 [21] Yamaguchi T,Yanagisawa K,Sugiyama R,et al. NKX2-1/TITF1/TTF-1-induced ROR1 is required to sustain EGFR survival signaling in lung adenocarcinoma[J]. Cancer Cell,2012,21(3):348-361. doi: 10.1016/j.ccr.2012.02.008 [22] 曹雨婷,郭中原,刘晓谦,等. 表皮生长因子受体酪氨酸激酶抑制剂研究进展[J]. 中国药学杂志,2023,58(22):2016-2027. [23] 龙明鹏. 基于AKT/mTOR通路研究小干扰RNA沉默ROR1抑制肺腺癌转移和侵袭的分子机制[D]. 成都:成都中医药大学,2020. [24] Liu Y,Yang H,Chen T,et al. Silencing of receptor tyrosine kinase ROR1 inhibits tumor-cell proliferation via PI3K/AKT/mTOR signaling pathway in lung adenocarcinoma[J]. PLoS One,2015,10(5):e0127092. doi: 10.1371/journal.pone.0127092 [25] Xu N,Qiao L,Yin L,et al. Long noncoding RNA ROR1-AS1 enhances lung adenocarcinoma metastasis and induces epithelial-mesenchymal transition by sponging miR-375[J]. J BUON,2019,24(6):2273-2279. [26] 马文琦,何鑫,张红丽,等. 下调结直肠癌细胞受体酪氨酸激酶样孤儿受体抑制细胞生长并促进其凋亡[J]. 细胞与分子免疫学杂志,2016,32(5):655-659,665. -
点击查看大图
图(2) / 表(3)
计量
- 文章访问数: 728
- HTML全文浏览量: 768
- PDF下载量: 26
- 被引次数: 0
