Cathepsin E is a marker of gastric differentiation and signet-ring cell carcinoma of stomach: a novel suggestion on gastric tumorigenesis.
Cathepsin E is a marker of gastric differentiation and signet-ring cell carcinoma of stomach: a novel suggestion on gastric tumorigenesis.
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DOI：
10.1371/journal.pone.0056766
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Koike K
中科院分区：
文献类型：
--
作者：
Konno-Shimizu M;Yamamichi N;Inada K;Kageyama-Yahara N;Shiogama K;Takahashi Y;Asada-Hirayama I;Yamamichi-Nishina M;Nakayama C;Ono S;Kodashima S;Fujishiro M;Tsutsumi Y;Ichinose M;Koike K
胃癌（GC）呈现出各种组织学特征，但其多样性背后的机制很少被阐明。主要分为高分化管状腺癌（tub1）、中分化管状腺癌（tub2）、低分化管状腺癌（por）、印戒细胞癌（sig）、粘液腺癌（muc）和乳头状腺癌（pap）。通过筛选，我们发现组织蛋白酶E（CTSE）在sig型GC细胞系中普遍表达，偶尔在por型中表达，在tub1/tub2型GC细胞系中很少表达。在手术切除的标本中，CTSE 免疫染色分为 50/51 sig 型（98.0%）、3/10 tube1 型（30.0%）、7/18 tube2 型（38.9%）、15/26 por 型（57.7%）、4/10 pap 型（40.0%）和 0/3 muc 型(0.0%) 气相色谱。在内镜切除标本中，6/7 sig型（85.7%）、7/52 tube1型（13.7%）、5/12 tube2型（41.7%）、2/7 pap型（28.6%）GC和0/6腺瘤（0.0%）表达CTSE。对于非恶性组织，CTSE在正常胃底、幽门、贲门腺中普遍表达，而在其他消化器官中几乎不表达。胃癌前肠化生CTSE多见于胃肠混合型，单纯肠型缺乏。 CTSE表达与胃标志物MUC5AC呈正相关（p<0.0001），与肠道标志物MUC2呈负相关（p = 0.0019）。对于sig型GC，在肿瘤和背景粘膜中，MUC5AC和CTSE的表达较高，而MUC2的表达较低，表明sig型GC反映了背景粘膜的特征。对于胃腺瘤和tub1/tub2型GC，更多的未分化肿瘤倾向于在肿瘤中表现出较高的CTSE和MUC5AC表达以及较低的MUC2表达，但它们在背景粘膜中倾向于表现出较低的CTSE、MUC5AC和MUC2表达。这些表明具有更强的胃特性和更弱的肠道特性的更恶性的胃腺癌往往源自胃和肠道特性均下降的背景粘膜。总之，CTSE是胃分化和印戒细胞癌的标志物，有望揭示胃肿瘤发生的机制。
Gastric cancer (GC) presents various histological features, though the mechanism underlying its diversity is seldom elucidated. It is mainly classified into well differentiated tubular adenocarcinoma (tub1), moderately differentiated tubular adenocarcinoma (tub2), poorly differentiated adenocarcinoma (por), signet-ring cell carcinoma (sig), mucinous adenocarcinoma (muc), and papillary adenocarcinoma (pap). By screening, we found cathepsin E (CTSE) expresses universally in sig-type, occasionally in por-type, and rarely in tub1/tub2-type GC cell lines. In surgically-resected specimens, CTSE was immunostained in 50/51 sig-type (98.0%), 3/10 tub1-type (30.0%), 7/18 tub2-type (38.9%), 15/26 por-type (57.7%), 4/10 pap-type (40.0%), and 0/3 muc-type (0.0%) GC. In endoscopically-resected specimens, 6/7 sig-type (85.7%), 7/52 tub1-type (13.7%), 5/12 tub2-type (41.7%), 2/7 pap-type (28.6%) GC and 0/6 adenoma (0.0%) expressed CTSE. For non-malignant tissues, CTSE is universally expressed in normal fundic, pyloric, and cardiac glands of stomach, but hardly in other digestive organs. In the precancerous intestinal metaplasia of stomach, CTSE is mostly observed in mixed gastric-and-intestinal type and deficient in solely-intestinal type. CTSE expression is positively correlated with gastric marker MUC5AC (p<0.0001) and negatively correlated with intestinal marker MUC2 (p = 0.0019). For sig-type GC, in both tumors and background mucosa, expression of MUC5AC and CTSE is high whereas that of MUC2 is low, indicating that sig-type GC reflects the features of background mucosa. For gastric adenoma and tub1/tub2-type GC, more undifferentiated tumors tend to show higher expression of CTSE with MUC5AC and lower expression of MUC2 in tumors, but they tend to present lower expression of CTSE, MUC5AC and MUC2 in background mucosa. These suggest that more malignant gastric adenocarcinoma with stronger gastric and weaker intestinal properties tend to arise from background mucosa with decreased both gastric and intestinal features. In conclusion, CTSE is a marker of both gastric differentiation and signet-ring cell carcinoma, which should shed light on the mechanism of gastric tumorigenesis.
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影响因子：
29.4
作者：
Hinoi, T;Lucas, PC;Fearon, ER
通讯作者：
Fearon, ER
DOI：
10.1111/apm.1965.64.1.31
发表时间：
1965-01-01
期刊：
ACTA PATHOLOGICA ET MICROBIOLOGICA SCANDINAVICA
影响因子：
--
作者：
LAUREN, P
通讯作者：
LAUREN, P
影响因子：
24.5
作者：
Grötzinger, C;Kneifel, J;Gessner, R
通讯作者：
Gessner, R
影响因子：
7.4
作者：
通讯作者：
--
影响因子：
9.6
作者：
Lee, J. H.;Choi, I. J.;Ryu, K. W.
通讯作者：
Ryu, K. W.