Concurrent Overexpression of Two Hyaluronidases, KIAA1199 and TMEM2, Strongly Predicts Shorter Survival After Resection in Pancreatic Ductal Adenocarcinoma
Concurrent Overexpression of Two Hyaluronidases, KIAA1199 and TMEM2, Strongly Predicts Shorter Survival After Resection in Pancreatic Ductal Adenocarcinoma
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DOI：
10.1097/mpa.0000000000002106
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发表时间：
2022-08
期刊：
影响因子：
2.9
通讯作者：
Yuzan Kudo;Norihiro Sato;Takuya Oba;Yasuhiro Adachi;Takao Amaike;Atsuhiro Koga;Shiro Kohi;H. Noguchi;T. Nakayama;K. Hirata
中科院分区：
文献类型：
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作者：
Yuzan Kudo;Norihiro Sato;Takuya Oba;Yasuhiro Adachi;Takao Amaike;Atsuhiro Koga;Shiro Kohi;H. Noguchi;T. Nakayama;K. Hirata
目的胰腺导管腺癌（PDAC）以透明质酸代谢加速为特征。我们以前的研究表明，PDAC中两种新鉴定的透明质酸酶KIAA 1199和跨膜蛋白2（TMEM 2）的表达增加。然而，这两种透明质酸酶之间的关系尚不清楚。在本研究中，我们研究了PDAC中KIAA 1199和TMEM 2表达之间的相关性。方法采用实时荧光定量逆转录聚合酶链反应（RT-PCR）技术，检测11株PDAC细胞系和12例PDAC患者冰冻组织中KIAA 1199和TMEM 2 mRNA的表达。我们使用免疫组化研究KIAA 1199和TMEM 2在92例接受手术切除的PDAC患者的存档组织中的表达模式。我们根据KIAA 1199和TMEM 2的表达模式比较了4组之间的生存率。结果在PDAC细胞系和组织中，KIAA 1199和TMEM 2 mRNA表达均呈显著正相关。免疫组化分析发现，KIAA 1199和TMEM 2低表达患者的中位总生存期为30.2个月，而两者高表达患者的中位总生存期为12.5个月。KIAA 1199和TMEM 2高表达的患者生存期明显短于其他患者组。结论这两种透明质酸酶的同时过表达可能是PDAC的一个强有力的预后标志。
Objectives Pancreatic ductal adenocarcinoma (PDAC) is characterized by accelerated hyaluronan metabolism. Our previous studies have shown increased expression of 2 newly identified hyaluronidases, KIAA1199 and transmembrane protein 2 (TMEM2), in PDAC. However, the relationship between these 2 hyaluronidases is unknown. In the present study, we investigated the correlation between KIAA1199 and TMEM2 expression in PDAC. Methods Using quantitative real-time reverse transcription polymerase chain reaction, we analyzed KIAA1199 and TMEM2 mRNA expression in 11 PDAC cell lines and frozen tissues from 12 patients with PDAC. We used immunohistochemistry to investigate expression patterns of KIAA1199 and TMEM2 in archival tissues obtained from 92 patients with PDAC who underwent surgical resection. We compared survival between 4 groups according to expression patterns of KIAA1199 and TMEM2. Results We found a significantly positive correlation between KIAA1199 and TMEM2 mRNA in PDAC cell lines and tissues. Immunohistochemical analysis found that median overall survival was 30.2 months in patients with low expression of KIAA1199 and TMEM2 and 12.5 months in those with high expression of both. Patients with high expression of KIAA1199 and TMEM2 had significantly shorter survival than other patient groups. Conclusions Concurrent overexpression of these 2 hyaluronidases could be a strong prognostic marker in PDAC.