PRSS1 Upregulation Predicts Platinum Resistance in Ovarian Cancer Patients.
PRSS1 Upregulation Predicts Platinum Resistance in Ovarian Cancer Patients.
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PRSS1 上调可预测卵巢癌患者的铂类耐药性
DOI：
10.3389/fcell.2020.618341
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发表时间：
2020
影响因子：
5.5
通讯作者：
Lou G
中科院分区：
文献类型：
--
作者：
Xing L;Tian S;Mi W;Zhang Y;Zhang Y;Zhang Y;Xu F;Zhang C;Lou G
卵巢癌是妇科恶性肿瘤中最常见的死亡原因。在完成铂类化疗的患者中，共有80%的患者在2年内复发并产生耐药性。在本研究中，我们从癌症基因组图谱数据库中获得了患者完整的铂类（顺铂和卡铂）药物信息，然后将其分为两类：耐药和敏感性。差异分析筛选与铂类药物疗效相关的差异表达基因。随后，我们将DE基因作为种子节点标注到蛋白质-蛋白质相互作用网络中，并通过随机游走对其进行分析。最后，选择第二位的丝氨酸蛋白酶1基因（PRSS 1）作为候选基因进行验证分析。在Oncomine和cBio Cancer Genomic Portal数据库中持续研究了PRSS 1的表达模式，揭示了PRSS 1在卵巢癌形成中的关键作用。此后，我们通过组织学和细胞学实验对PRSS 1对卵巢癌的铂类反应进行了深入的探讨。定量实时聚合酶链反应和蛋白质印迹分析结果表明，铂耐药样品（组织/细胞）中的PRSS 1表达水平显着高于铂敏感样品。通过细胞转染实验，我们观察到PRSS 1的敲低降低了卵巢癌细胞对顺铂的耐药性。同时，PRSS 1的过表达增加了顺铂的耐药性。总之，我们确定了一个新的风险基因PRSS 1相关的卵巢癌铂反应，并确认其关键作用，使用多个水平的低通量实验，揭示了一个新的治疗策略的基础上，一个新的靶因子克服卵巢癌顺铂耐药。
Ovarian cancer is the most frequent cause of death among gynecologic malignancies. A total of 80% of patients who have completed platinum-based chemotherapy suffer from relapse and develop resistance within 2 years. In the present study, we obtained patients' complete platinum (cisplatin and carboplatin) medication information from The Cancer Genome Atlas database and then divided them into two categories: resistance and sensitivity. Difference analysis was performed to screen differentially expressed genes (DEgenes) related to platinum response. Subsequently, we annotated DEgenes into the protein–protein interaction network as seed nodes and analyzed them by random walk. Finally, second-ranking protease serine 1 gene (PRSS1) was selected as a candidate gene for verification analysis. PRSS1's expression pattern was continuously studied in Oncomine and cBio Cancer Genomic Portal databases, revealing the key roles of PRSS1 in ovarian cancer formation. Hereafter, we conducted in-depth explorations on PRSS1's platinum response to ovarian cancer through tissue and cytological experiments. Quantitative real-time polymerase chain reaction and Western blot assay results indicated that PRSS1 expression levels in platinum-resistant samples (tissue/cell) were significantly higher than in samples sensitive to platinum. By cell transfection assay, we observed that knockdown of PRSS1 reduced the resistance of ovarian cancer cells to cisplatin. Meanwhile, overexpression of PRSS1 increased the resistance to cisplatin. In conclusion, we identified a novel risk gene PRSS1 related to ovarian cancer platinum response and confirmed its key roles using multiple levels of low-throughput experiments, revealing a new treatment strategy based on a novel target factor for overcoming cisplatin resistance in ovarian cancer.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
4.6
作者：
Dar S;Chhina J;Mert I;Chitale D;Buekers T;Kaur H;Giri S;Munkarah A;Rattan R
通讯作者：
Rattan R
影响因子：
5.5
作者：
Chen, Ying;Cao, Xiao-Yun;Wang, Hui
通讯作者：
Wang, Hui
DOI：
10.1016/j.jamcollsurg.2018.01.059
发表时间：
2018-06-01
影响因子：
5.2
作者：
Erinjeri, Neeta J.;Nicolson, Norman G.;Carling, Tobias
通讯作者：
Carling, Tobias
影响因子：
11.2
作者：
Hendrix, ND;Wu, R;Cho, KR
通讯作者：
Cho, KR