Li Wen-Xiang, Zheng Jia-Jia, Zhao Gang, Lyu Chen-Tao, Lu Wei-Qi
Department of General Surgery, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
World J Surg Oncol. 2021 Apr 7;19(1):100. doi: 10.1186/s12957-021-02212-7.
Down syndrome critical region 1 (DSCR1) is associated with carcinogenesis and tumor growth in several types of malignancy. However, little is known about the role of DSCR1 in CRC progression. The present study aimed to elucidate the clinicopathological significance, prognostic, and function roles of DSCR1 in CRC.
Firstly, we analyzed DSCR1 expression in 58 paired CRC samples and Oncomine database. Then, we analyzed DSCR1 expression in two independent CRC cohorts (test cohort: n = 70; validation cohort: n = 58) and tested its overall survival (OS) by Kaplan-Meier survival analyses. Finally, we overexpressed DSCR1 in two CRC cell lines DLD1 and LoVo and analyzed its effect on cell cycle and senescence.
DSCR1 expression was significantly decreased in CRC samples and associated with clinicopathologic features of CRC patients, such as tumor size, lymph node metastasis, and TNM stage. CRC patients with low expression of DSCR1 had shorter overall survival (OS). Kaplan-Meier survival analyses showed that the expression of DSCR1 was significant factor for OS in both cohorts. Multiple Cox regression analysis showed that DSCR1 expression was an independent prognostic marker for OS in test cohort. Overexpression of DSCR1 isoform 4 (DSCR1-4) increased p21, p16, p-NFAT1, and p-NFAT2, while decreased CDK2, CDK4, and Cyclin D1 in CRC cells. In addition, overexpression of DSCR1-4 prevented proliferation and colony formation, and induced senescence in vitro. Moreover, overexpression of DSCR1-4 inhibited tumor growth and tumor angiogenesis in vivo.
Our study found high expression of DSCR1 contributes to favorable prognosis of CRC patients and prevents cell cycle and proliferation of CRC cells, indicating a critical tumor suppressive role in CRC progression.
唐氏综合征关键区域1（DSCR1）与多种恶性肿瘤的致癌作用和肿瘤生长相关。然而，关于DSCR1在结直肠癌进展中的作用知之甚少。本研究旨在阐明DSCR1在结直肠癌中的临床病理意义、预后及功能作用。
首先，我们分析了58对结直肠癌样本和Oncomine数据库中DSCR1的表达。然后，我们在两个独立的结直肠癌队列（测试队列：n = 70；验证队列：n = 58）中分析了DSCR1的表达，并通过Kaplan-Meier生存分析测试其总生存期（OS）。最后，我们在两种结直肠癌细胞系DLD1和LoVo中过表达DSCR1，并分析其对细胞周期和衰老的影响。
DSCR1在结直肠癌样本中的表达显著降低，并与结直肠癌患者的临床病理特征相关，如肿瘤大小、淋巴结转移和TNM分期。DSCR1低表达的结直肠癌患者总生存期较短。Kaplan-Meier生存分析表明，DSCR1的表达在两个队列中都是总生存期的显著因素。多因素Cox回归分析表明，DSCR1表达是测试队列中总生存期的独立预后标志物。DSCR1亚型4（DSCR1-4）的过表达增加了p21、p16、p-NFAT1和p-NFAT2，同时降低了结直肠癌细胞中的CDK2、CDK4和细胞周期蛋白D1。此外，DSCR1-4的过表达在体外阻止了细胞增殖和集落形成，并诱导了衰老。而且，DSCR1-4的过表达在体内抑制了肿瘤生长和肿瘤血管生成。
我们的研究发现DSCR1的高表达有助于结直肠癌患者的良好预后，并阻止结直肠癌细胞的细胞周期和增殖，表明其在结直肠癌进展中具有关键的肿瘤抑制作用。
