Relationships of expressions of Calponin 1 and tumor ubiquitin-specific protease 1 with clinical pathological characteristics in gastric cancer tissues
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摘要:目的
探讨胃癌组织中调宁蛋白1(Calponin 1)、肿瘤泛素异肽酶1(OTUB1)表达与临床病理特征的关系及预后价值。
方法选取98例胃癌患者为研究对象。采用qPCR检测胃癌组织中Calponin 1 mRNA、OTUB1 mRNA的表达; 采用免疫组织化学方法检测Calponin 1、OTUB1的蛋白表达; 绘制Kaplan-Meier曲线比较不同Calponin 1、OTUB1表达的胃癌患者的生存差异; 采用Cox回归模型筛选胃癌预后的影响因素。
结果与癌旁组织比较, 胃癌组织中Calponin 1 mRNA、OTUB1 mRNA表达量较高，差异有统计学意义(P < 0.05)。胃癌组织中Calponin 1、OTUB1蛋白阳性表达率为63.27%、65.31%, 高于癌旁组织的6.12%、8.16%, 差异有统计学意义(P < 0.001)。TNM分期Ⅲ期、有淋巴结转移的胃癌组织中Calponin 1、OTUB1蛋白表达水平升高，差异有统计学意义(P < 0.05)。Calponin 1阳性组3年总生存率为45.16%(28/62), 低于阴性组的83.33%(30/36), 差异有统计学意义(Log-rank χ2=12.990, P < 0.001); OTUB1阳性组3年总生存率为45.31%(29/64), 低于阴性组的85.29%(29/34), 差异有统计学意义(Log-rank χ2=14.880, P < 0.001)。多因素Cox回归结果显示, Calponin 1阳性、OTUB1阳性、TNM分期Ⅲ期、有淋巴结转移是胃癌患者死亡的危险因素(P < 0.001)。
结论胃癌组织中Calponin 1、OTUB1表达上调, 与TNM分期、淋巴结转移有关。
Abstract:ObjectiveTo investigate the relationships of the expression of Calponin 1 and tumor ubiquitin-specific protease 1 (OTUB1) with clinicopathological features in gastric cancer tissues as well as their prognostic values.
MethodsA total of 98 patients with gastric cancer were enrolled in this study. The qPCR was used to detect the expression levels of Calponin 1 mRNA and OTUB1 mRNA in gastric cancer tissues; the immunohistochemical staining was performed to detect the protein expression levels of Calponin 1 and OTUB1; the Kaplan-Meier curve was plotted to compare the survival differences among gastric cancer patients with different expression levels of Calponin 1 and OTUB1; the Cox regression model was used to screen the influencing factors of prognosis in gastric cancer.
ResultsCompared with adjacent tissues, the expression levels of Calponin 1 mRNA and OTUB1 mRNA in gastric cancer tissues were significantly higher (P < 0.05). The positive expression rates of Calponin 1 and OTUB1 protein in gastric cancer tissues were 63.27% and 65.31% respectively, which were significantly higher than 6.12% and 8.16% in adjacent tissues (P < 0.001). The expression levels of Calponin 1 and OTUB1 proteins were increased significantly in gastric cancer tissues of cases with stage Ⅲ of TNM staging and lymph node metastasis (P < 0.05). The 3-year overall survival rate was 45.16% (28/62) in the Calponin 1-positive group, which was significantly lower than 83.33% (30/36) in the Calponin 1-negative group (Log-rank χ2=12.990, P < 0.001). The 3-year overall survival rate was 45.31% (29/64) in the OTUB1-positive group, which was significantly lower than 85.29% (29/34) in the OTUB1-negative group (Log-rank χ2=14.880, P < 0.001). The results of multivariate Cox regression showed that Calponin 1 positivity, OTUB1 positivity, stage Ⅲ of TNM staging, and lymph node metastasis were risk factors for death in gastric cancer patients (P < 0.001).
ConclusionThe expressions of Calponin 1 and OTUB1 are upregulated in gastric cancer tissues and are related to TNM staging and lymph node metastasis.
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Keywords:
- gastric cancer /
- Calponin 1 /
- tumor ubiquitin-specific protease 1 /
- tumor pathology /
- prognosis /
- risk factors
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图 1 胃癌组织与癌旁组织中Calponin 1 mRNA、OTUB1 mRNA表达比较
Calponin 1: 调宁蛋白1; OTUB1: 肿瘤泛素异肽酶1。与癌旁组织比较, *P < 0.05。
表 1 不同组织中Calponin 1、OTUB1蛋白阳性表达[n(%)]
样本 n Calponin 1蛋白阳性 OTUB1蛋白阳性 胃癌组织 98 62(63.27) 64(65.31) 癌旁组织 98 6(6.12)*** 8(8.16)*** 与胃癌组织比较, * * * P < 0.001。 
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表 2 Calponin 1、OTUB1蛋白阳性表达与胃癌临床参数的关系[n(%)]
临床参数 分类 n Calponin 1阳性 χ2 P OTUB1阳性 χ2 P 年龄 < 60岁 43 26(60.47) 0.259 0.611 26(60.47) 0.792 0.373 ≥60岁 55 36(65.45) 38(69.09) 性别 男 54 35(64.81) 0.124 0.724 37(68.52) 0.548 0.459 女 44 27(61.36) 27(61.36) 分化程度 中高分化 56 32(57.14) 2.108 0.147 33(58.93) 2.346 0.126 低分化 42 30(71.43) 31(73.81) 肿瘤直径 ≤5 cm 60 34(56.67) 2.899 0.089 37(61.67) 0.905 0.342 >5 cm 38 28(73.68) 27(71.05) 肿瘤位置 胃底贲门部 20 15(75.00) 1.493 0.342 16(80.00) 2.540 0.281 胃体部 28 17(60.71) 18(64.29) 幽门胃窦部 50 30(60.00) 30(60.00) 淋巴结转移 无 50 26(52.00) 5.574 0.018 26(52.00) 7.977 0.005 有 48 36(75.00) 38(79.17) TNM分期 Ⅰ~Ⅱ期 60 30(50.00) 11.716 0.001 31(51.67) 12.705 < 0.001 Ⅲ期 38 32(84.21) 33(86.84)
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表 3 多因素Cox回归分析
因素 β SE Wald χ2 P HR 95%CI 有淋巴结转移 0.513 0.138 13.819 < 0.001 1.670 1.274~2.189 TNM分期Ⅲ期 0.460 0.132 12.144 < 0.001 1.584 1.223~2.052 Calponin 1阳性 0.402 0.154 6.814 < 0.001 1.495 1.105~2.021 OTUB1阳性 0.494 0.152 10.563 < 0.001 1.639 1.217~2.208
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[1] YANG W J, ZHAO H P, YU Y, et al. Updates on global epidemiology, risk and prognostic factors of gastric cancer[J]. World J Gastroenterol, 2023, 29(16): 2452-2468. doi: 10.3748/wjg.v29.i16.2452
[2] CHEN D X, FU M T, CHI L J, et al. Prognostic and predictive value of a pathomics signature in gastric cancer[J]. Nat Commun, 2022, 13(1): 6903. doi: 10.1038/s41467-022-34703-w
[3] CHOO Y Y, SAKAI T, KOMATSU S, et al. Calponin 1 contributes to myofibroblast differentiation of human pleural mesothelial cells[J]. Am J Physiol Lung Cell Mol Physiol, 2022, 322(3): L348-L364. doi: 10.1152/ajplung.00289.2021
[4] ZHOU H L, KE J Y, LIU C H, et al. Potential prognostic and immunotherapeutic value of calponin 1: a pan-cancer analysis[J]. Front Pharmacol, 2023, 14: 1184250. doi: 10.3389/fphar.2023.1184250
[5] LI Y J, CHEN C Y, KUO Y S, et al. OTUB1 contributes to the stability and function of Influenza A virus NS2[J]. PLoS Pathog, 2024, 20(5): e1012279. doi: 10.1371/journal.ppat.1012279
[6] SHERYAZDANOVA A, AMOEDO N D, DUFOUR S, et al. The deubiquitinase OTUB1 governs lung cancer cell fitness by modulating proteostasis of OXPHOS proteins[J]. Biochim Biophys Acta Mol Basis Dis, 2023, 1869(7): 166767. doi: 10.1016/j.bbadis.2023.166767
[7] 李小钰, 黄青, 吴雨濛, 等. 2022年全球癌症统计报告的窄谱总结和展望[J]. 肿瘤防治研究, 2024, 51(5): 307-312. [8] KOMORI K, KANO K, ANDO S, et al. Clinicopathological characteristics and prognosis of mucinous gastric cancer[J]. Anticancer Res, 2023, 43(6): 2865-2871. doi: 10.21873/anticanres.16456
[9] FENG H Z, WANG H, TAKAHASHI K, et al. Double deletion of calponin 1 and calponin 2 in mice decreases systemic blood pressure with blunted length-tension response of aortic smooth muscle[J]. J Mol Cell Cardiol, 2019, 129: 49-57. doi: 10.1016/j.yjmcc.2019.01.026
[10] WANG Z, LI T E, CHEN M, et al. miR-106b-5p contributes to the lung metastasis of breast cancer via targeting CNN1 and regulating Rho/ROCK1 pathway[J]. Aging, 2020, 12(2): 1867-1887. doi: 10.18632/aging.102719
[11] LIU W S, FU X G, LI R M. CNN1 regulates the DKK1/Wnt/β-catenin/c-myc signaling pathway by activating TIMP2 to inhibit the invasion, migration and EMT of lung squamous cell carcinoma cells[J]. Exp Ther Med, 2021, 22(2): 855. doi: 10.3892/etm.2021.10287
[12] LU Y F, JIN Z J, HOU J Y, et al. Calponin 1 increases cancer-associated fibroblasts-mediated matrix stiffness to promote chemoresistance in gastric cancer[J]. Matrix Biol, 2023, 115: 1-15. doi: 10.1016/j.matbio.2022.11.005
[13] LEE J, YOON J H, LEE E, et al. Immune response and mesenchymal transition of papillary thyroid carcinoma reflected in ultrasonography features assessed by radiologists and deep learning[J]. J Adv Res, 2024, 62: 219-228. doi: 10.1016/j.jare.2023.09.043
[14] ZHANG J L, DU B B, ZHANG D H, et al. OTUB1 alleviates NASH through inhibition of the TRAF6-ASK1 signaling pathways[J]. Hepatology, 2022, 75(5): 1218-1234. doi: 10.1002/hep.32179
[15] HAN X, REN C E, LU C, et al. Deubiquitination of MYC by OTUB1 contributes to HK2 mediated glycolysis and breast tumorigenesis[J]. Cell Death Differ, 2022, 29(9): 1864-1873. doi: 10.1038/s41418-022-00971-8
[16] WENG W W, ZHANG Q Y, XU M D, et al. OTUB1 promotes tumor invasion and predicts a poor prognosis in gastric adenocarcinoma[J]. Am J Transl Res, 2016, 8(5): 2234-2244. http://ajtr.org/files/ajtr0023747.pdf
[17] ZHOU Y, JIA Q Z, MENG X Q, et al. ERRα regulates OTUB1 expression to promote colorectal cancer cell migration[J]. J Cancer, 2019, 10(23): 5812-5819. doi: 10.7150/jca.30720
[18] LI D B, WANG Y H, DONG C, et al. CST1 inhibits ferroptosis and promotes gastric cancer metastasis by regulating GPX4 protein stability via OTUB1[J]. Oncogene, 2023, 42(2): 83-98. doi: 10.1038/s41388-022-02537-x
[19] ZHU D, XU R D, HUANG X P, et al. Deubiquitinating enzyme OTUB1 promotes cancer cell immunosuppression via preventing ER-associated degradation of immune checkpoint protein PD-L1[J]. Cell Death Differ, 2021, 28(6): 1773-1789. doi: 10.1038/s41418-020-00700-z
[20] LIN H B, HAN Y T, SANG Y C, et al. OTUD1 enhances gastric cancer aggressiveness by deubiquitinating EBV-encoded protein BALF1 to stabilize the apoptosis inhibitor Bcl-2[J]. Biochim Biophys Acta Mol Basis Dis, 2024, 1870(5): 167132. doi: 10.1016/j.bbadis.2024.167132
[21] LIAO Y H, LIANG J M, WANG Y Z, et al. Target deubiquitinase OTUB1 as a therapeatic strategy for BLCA via β-catenin/necroptosis signal pathway[J]. Int J Biol Sci, 2024, 20(10): 3784-3801. doi: 10.7150/ijbs.94013
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