Identification of laminin γ2 as a prognostic and predictive biomarker for determining response to gemcitabine-based therapy in pancreatic ductal adenocarcinoma.
Identification of laminin γ2 as a prognostic and predictive biomarker for determining response to gemcitabine-based therapy in pancreatic ductal adenocarcinoma.
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鉴定层粘连蛋白γ - 2作为确定以吉西他滨为基础的胰腺导管腺癌治疗反应的预后和预测性生物标志物。
DOI：
10.1016/j.ejca.2020.12.031
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Goel A
中科院分区：
文献类型：
--
作者：
Okada Y;Nishiwada S;Yamamura K;Sho M;Baba H;Takayama T;Goel A
胰腺导管腺癌（pancreatic ductal adenocarcinoma，PDAC）是最致命的恶性肿瘤之一。虽然细胞外基质（ECM）成分在PDAC发病机制和介导化疗耐药性中起着不可或缺的作用，但其在预测PDAC患者对化疗反应中的作用仍不清楚。我们通过分析来自423名患者（GSE 71729、GSE 21501和TCGA）的全基因组转录组谱数据进行了系统的生物标志物发现，以预测总生存期（OS）。随后在270例PDAC患者的两个独立临床队列（训练队列; n = 121和验证队列; n = 149）中验证了这一点。此外，我们研究了来自51名患有不可切除癌症的PDAC患者的EUS-FNA活检标本，以预测对吉西他滨治疗的治疗反应。经过严格的生物信息学分析，我们确定LAMC 2是所有三个PDAC数据集中的显著预后因素（GSE 71729，HR = 2.04，P = 0.002; GSE 21501，HR = 2.17，P = 0.031; TCGA，HR = 2.57，P <0.001）。PDAC患者中的高LAMC 2表达与训练组（P <0.001，P <0.001）和验证组（P = 0.001，P = 0.003）中显著差的OS和无复发生存期（RFS）相关。更重要的是，LAMC 2表达可以有力地鉴别出患有不可切除疾病的PDAC患者和对基于吉西他滨的治疗有反应的PDAC患者（AUC = 0.79; 95%CI，0.65 - 0.89）。单变量logistic回归分析显示，LAMC 2高表达是预测PDAC患者对吉西他滨反应不良的唯一因素（比值比[OR]= 4.90; 95% CI，1.45 - 16.6; P = 0.011）。我们的结论是，LAMC 2是一种新的预后和预测生物标志物吉西他滨为基础的治疗在辅助和姑息设置;这可能有显着的影响，在PDAC患者的精确性和个性化治疗。
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. While the extracellular matrix (ECM) components plays an integral role in PDAC pathogenesis and mediating chemoresistance, its role in predicting response to chemotherapy in PDAC patients remains unclear. We performed a systematic biomarker discovery by analyzing genomewide transcriptomic profiling data from 423 patients (GSE71729, GSE21501 and TCGA) for predicting overall survival (OS). This was subsequently validated in two independent clinical cohorts of 270 PDAC patients (training cohort; n=121 and validation cohort; n=149). In addition, we investigated EUS-FNA biopsy specimens from 51 PDAC patients with an unresectable cancer for predicting therapeutic response to gemcitabine-based therapy. Following rigorous bioinformatic analysis, we identified LAMC2 to be a significant prognostic factor in all three PDAC datasets (GSE71729, HR=2.04, P=0.002; GSE21501, HR=2.17, P=0.031; TCGA, HR=2.57, P<0.001). High LAMC2 expression in PDAC patients associated with a significantly poor OS and relapse-free survival (RFS) in both training (P<0.001, P<0.001) and validation cohorts (P=0.001, P=0.003). More importantly, LAMC2 expression robustly identified PDAC patients with unresectable disease and those who responded to gemcitabine-based therapy (AUC= 0.79; 95%CI, 0.65–0.89). The univariate logistic regression analysis revealed that high LAMC2 expression was the only factor that predicted poor response to gemcitabine in PDAC patients (Odds Ratio [OR]=4.90; 95% CI, 1.45–16.6; P=0.011). We conclude that LAMC2 is a novel prognostic and predictive biomarker for gemcitabine-based therapy in both adjuvant and palliative setting; which could have significant impact in precision and individualized treatment of PDAC patients.
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影响因子：
28.2
作者：
Tiriac H;Belleau P;Engle DD;Plenker D;Deschênes A;Somerville TDD;Froeling FEM;Burkhart RA;Denroche RE;Jang GH;Miyabayashi K;Young CM;Patel H;Ma M;LaComb JF;Palmaira RLD;Javed AA;Huynh JC;Johnson M;Arora K;Robine N;Shah M;Sanghvi R;Goetz AB;Lowder CY;Martello L;Driehuis E;LeComte N;Askan G;Iacobuzio-Donahue CA;Clevers H;Wood LD;Hruban RH;Thompson E;Aguirre AJ;Wolpin BM;Sasson A;Kim J;Wu M;Bucobo JC;Allen P;Sejpal DV;Nealon W;Sullivan JD;Winter JM;Gimotty PA;Grem JL;DiMaio DJ;Buscaglia JM;Grandgenett PM;Brody JR;Hollingsworth MA;O'Kane GM;Notta F;Kim E;Crawford JM;Devoe C;Ocean A;Wolfgang CL;Yu KH;Li E;Vakoc CR;Hubert B;Fischer SE;Wilson JM;Moffitt R;Knox J;Krasnitz A;Gallinger S;Tuveson DA
通讯作者：
Tuveson DA
影响因子：
14.9
作者：
Harris, MA;Clark, J;White, R
通讯作者：
White, R
影响因子：
9
作者：
Groot, Vincent P.;Gemenetzis, Georgios;He, Jin
通讯作者：
He, Jin
影响因子：
29.4
作者：
Marechal, Raphael;Bachet, Jean-Baptiste;Van Laethem, Jean-Luc
通讯作者：
Van Laethem, Jean-Luc
影响因子：
9.7
作者：
Li, Yan;Hong, JinWoo;Yun, Chae-Ok
通讯作者：
Yun, Chae-Ok