Prognostic value of functional SMAD4 localization in extrahepatic bile duct cancer.
Prognostic value of functional SMAD4 localization in extrahepatic bile duct cancer.
复制标题
DOI：
10.1186/s12957-022-02747-3
复制
发表时间：
2022-09-10
影响因子：
3.2
通讯作者：
Eguchi, Hidetoshi
中科院分区：
文献类型：
--
作者：
Takayama, Hirotoshi;Kobayashi, Shogo;Gotoh, Kunihito;Sasaki, Kazuki;Iwagami, Yoshifumi;Yamada, Daisaku;Tomimaru, Yoshito;Akita, Hirofumi;Asaoka, Tadafumi;Noda, Takehiro;Wada, Hiroshi;Takahashi, Hidenori;Tanemura, Masahiro;Doki, Yuichiro;Eguchi, Hidetoshi
SMAD4是tgf - β信号传导的关键介质，也是肝外胆管癌（eBDC）的突变基因之一。也有报道称SMAD4具有双重功能，通过沉默来致癌，通过信号传导来肿瘤侵袭/转移，这取决于肿瘤分期。我们之前在肿瘤侵袭前沿发现了比中心病变更多的核转移功能SMAD4。因此，我们研究了功能性SMAD4的定位（如侵袭区或转移灶）及其与化疗和放化疗的关系。我们对98例切除的eBDC标本进行了SMAD4免疫染色，并评估了SMAD4核在中心病变、侵袭前沿和转移淋巴结的功能形式。我们还研究了复发后化疗（n = 33）和新辅助放化疗（NAC-RT, n = 21）的影响以及使用回顾性数据的预后价值。在73例无NAC-RT的患者中，8.2%的患者SMAD4表达缺失，23.3%的患者SMAD4表达异质。没有SMAD4在任何部位表达的患者的总生存期（OS）明显低于其他患者（P = 0.014）。侵袭前沿表达SMAD4与较好的生存率相关（无复发生存率[RFS] P = 0.033; OS P = 0.047），转移淋巴结不表达SMAD4与较差的生存率相关（P = 0.011）。SMAD4高表达患者复发后预后较差（RFS P = 0.011; OS P = 0.056）。在切除标本的残余癌中，NAC-RT后SMAD4高表达（P = 0.039）。SMAD4蛋白表达缺失是可切除期eBDC患者预后不良的因素。然而，在eBDC中，功能性SMAD4的强度是化疗-放疗耐药和晚期恶性潜能的标志。在线版本包含补充材料，可在10.1186/s12957-022-02747-3获得。
SMAD4 is a key mediator of TGFβ signaling and one of the mutated genes in extrahepatic bile duct cancer (eBDC). It has been also reported that SMAD4 has dual functions, in carcinogenesis via silencing and in tumor invasion/metastasis via signaling, depending on tumor stage. We previously visualized more nuclear transitioning functional SMAD4 at the tumor invasion front than the central lesion. So, we investigated the localization of functional SMAD4 (e.g., invasion area or metastasis lesion) and its association with chemotherapy and chemo-radiation therapy. We performed SMAD4 immunostaining on 98 resected eBDC specimens and evaluated the presence of the functional form of nuclear SMAD4 at the central lesion, invasion front, and metastatic lymph node. We also examined the influence on chemotherapy after recurrence (n = 33) and neoadjuvant chemo-radiation therapy (NAC-RT, n = 21) and the prognostic value of using retrospective data. In 73 patients without NAC-RT, 8.2% had loss of SMAD4 expression and 23.3% had heterogeneous expression. Patients without SMAD4 expression at any site had significantly poorer overall survival (OS) than other patients (P = 0.014). Expression of SMAD4 at the invasion front was related to better survival (recurrence-free survival [RFS] P = 0.033; OS P = 0.047), and no SMAD4 expression at the metastatic lymph node was related to poorer OS (P = 0.011). The patients who had high SMAD4 expression had poorer prognosis after recurrence (RFS P = 0.011; OS P = 0.056). At the residual cancer in the resected specimen, SMAD4 was highly expressed after NAC-RT (P = 0.039). Loss of SMAD4 protein expression was a poor prognostic factor in eBDC at resectable stage. However, the intensity of functional SMAD4 in eBDC is a marker of resistance to chemo-radiotherapy and malignant potential at advanced stages. The online version contains supplementary material available at 10.1186/s12957-022-02747-3.
登录
查看更多内容
影响因子：
21.3
作者：
Vincent, Theresa;Neve, Etienne P. A.;Johnson, Jill R.;Kukalev, Alexander;Rojo, Federico;Albanell, Joan;Pietras, Kristian;Virtanen, Ismo;Philipson, Lennart;Leopold, Philip L.;Crystal, Ronald G.;Garcia de Herreros, Antonio;Moustakas, Aristidis;Pettersson, Ralf F.;Fuxe, Jonas
通讯作者：
Fuxe, Jonas
SMAD4 基因突变通过促进自噬使胰腺癌对放疗产生抵抗力
DOI：
10.1158/1078-0432.ccr-17-3435
发表时间：
2018-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Wang F;Xia X;Yang C;Shen J;Mai J;Kim HC;Kirui D;Kang Y;Fleming JB;Koay EJ;Mitra S;Ferrari M;Shen H
通讯作者：
Shen H
影响因子：
25.7
作者：
Montal R;Sia D;Montironi C;Leow WQ;Esteban-Fabró R;Pinyol R;Torres-Martin M;Bassaganyas L;Moeini A;Peix J;Cabellos L;Maeda M;Villacorta-Martin C;Tabrizian P;Rodriguez-Carunchio L;Castellano G;Sempoux C;Minguez B;Pawlik TM;Labgaa I;Roberts LR;Sole M;Fiel MI;Thung S;Fuster J;Roayaie S;Villanueva A;Schwartz M;Llovet JM
通讯作者：
Llovet JM
影响因子：
6.1
作者：
Yan Xue-qiang;Zhang Wei;Chen Xiao-ping
通讯作者：
Chen Xiao-ping
影响因子：
11.5
作者：
Alazzouzi, H;Alhopuro, P;Arango, D
通讯作者：
Arango, D