<abstract xmlns="http://www.w3.org/1999/xhtml">

<sec><h3>Introduction</h3>
<p>The tumor gene SMAD4 was genetically inactivated in approximately half of pancreatic cancer (PC) patients. The correlation of SMAD4 gene expression in PC and its prognosis remains inconclusive. The aim of this study was to evaluate the association between loss of SMAD4 expression and the outcome of resectable PC.</p>
</sec>
<sec><h3>Materials and Methods</h3>
<p>A systematic review of the relevant electronic databases was conducted between SMAD4 expression and the outcome of PC patients until December 2020, including PubMed, Web of Science, and the China Journal Net. A meta-analysis was performed using STATA 12.0 and pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate the strength of the association between SMAD4 gene expression and the prognosis of PC patients.</p>
</sec>
<sec><h3>Results</h3>
<p>Twelve studies were included. Our meta-analysis illustrated that there were no significant associations between the loss of SMAD4 gene expression and overall survival in resectable PC (HR=1.38, 95% CI 0.98–1.81). In addition, there was no evidence of publication bias, as showed by Begg's and Egger's test. There was no correlation between the loss of SMAD4 expression and local recurrence (OR=0.97, 95% CI 0.52–1.80, p=0.914), while the loss of SMAD4 gene expression was associated with increased risk of distant recurrence (OR=1.36, 95% CI 1.08–1.70, p=0.008).</p>
</sec>
<sec><h3>Conclusions</h3>
<p>After PC resection, the loss of SMAD4 gene expression was correlated with higher risk of distant recurrence, but not with local recurrence nor overall survival.</p>
</sec>
</abstract>

Introduction
The tumor gene SMAD4 was genetically inactivated in approximately half of pancreatic cancer (PC) patients. The correlation of SMAD4 gene expression in PC and its prognosis remains inconclusive. The aim of this study was to evaluate the association between loss of SMAD4 expression and the outcome of resectable PC.

Materials and Methods
A systematic review of the relevant electronic databases was conducted between SMAD4 expression and the outcome of PC patients until December 2020, including PubMed, Web of Science, and the China Journal Net. A meta-analysis was performed using STATA 12.0 and pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate the strength of the association between SMAD4 gene expression and the prognosis of PC patients.

Results
Twelve studies were included. Our meta-analysis illustrated that there were no significant associations between the loss of SMAD4 gene expression and overall survival in resectable PC (HR=1.38, 95% CI 0.98–1.81). In addition, there was no evidence of publication bias, as showed by Begg's and Egger's test. There was no correlation between the loss of SMAD4 expression and local recurrence (OR=0.97, 95% CI 0.52–1.80, p=0.914), while the loss of SMAD4 gene expression was associated with increased risk of distant recurrence (OR=1.36, 95% CI 1.08–1.70, p=0.008).

Conclusions
After PC resection, the loss of SMAD4 gene expression was correlated with higher risk of distant recurrence, but not with local recurrence nor overall survival.

Prognostic value of SMAD4 in resectable pancreatic cancer

First Affiliated Hospital of Jinan University

Department of General Surgery, Hwa Mei Hospital

University of Chinese Academy of Sciences

Ningbo Institute of Life and Health Industry

Postępy Higieny i Medycyny Doświadczalnej

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

{"article-title":"Prognostic value of SMAD4 in resectable pancreatic cancer"}

Introduction
The tumor gene SMAD4 was genetically inactivated in approximately half of pancreatic cancer (PC) patients. The correlation of SMAD4 gene...

Author, Year	Country	Group	Histology	Follow-up (Median/Months)	Method	Antibody (Dilution)	Cutoff (%)	Study Quality Score
Oshima M 2013 [15]	Japan	SMAD4+SMAD4−	PDAC	62/44	IHC	Santa 1:100	>0	8
Yamada S 2015 [16]	Japan	SMAD4+SMAD4−	PDAC	44/2659/45	IHC	Santa 1:100	>0	7
Herman JM 2018 [17]	USA	SMAD4+SMAD4−	PDAC	36/2145/43	IHC	----	>0	7
Tascilar M 2001 [18]	USA	SMAD4+SMAD4−	PAC	61/5078/60	IHC	Santa 1:100	>0	9
Biankin AV 2002 [19]	Australia	SMAD4+SMAD4−	PDAC	190/158	IHC	Santa	>5	7
Xu JZ 2019 [20]	China	SMAD4+SMAD4−	PDAC	30/39102/66	IHC	----	----	7
Ottenhof NA 2012 [21]	The Netherlands	SMAD4+SMAD4−	PDAC	35/43	IHC	Santa 1:300	>0	8
Shen J 2019 [22]	China	SMAD4+SMAD4−	PDAC	----	IHC	----	----	6
Toga T 2004 [23]	Japan	SMAD4+SMAD4−	IDC	6/737/38	IHC	Santa 1:100	>10	6
Bachet JB 2012 [24]	France	SMAD4+	PDAC	54	IHC	Santa 1:50	>0	9
Winter JM 2013 [25]	USA	SMAD4−	PDAC	48	IHC	Santa 1:800	>0	8
Shin SH 2017 [26]	Korea	SMAD4+	PDAC	----	IHC	Santa 1:100	>0	7

Prognostic value of SMAD4 in resectable pancreatic cancer

Article Category: Original Study

Publicado en línea: 09 ago 2022

Páginas: 324 - 332

Recibido: 12 jun 2021

Aceptado: 13 oct 2021

DOI: https://doi.org/10.2478/ahem-2022-0036

Palabras clave
SMAD4 gene, resection, pancreatic cancer, recurrence, overall survival

© 2022 Hui Su et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Fig. 1

Fig. 2

Fig. 3

Fig. 4

Fig. 5

Overview of the reviewed studies

Prognostic value of SMAD4 in resectable pancreatic cancer

Article Category: Original Study

Publicado en línea: 09 ago 2022

Páginas: 324 - 332

Recibido: 12 jun 2021

Aceptado: 13 oct 2021

DOI: https://doi.org/10.2478/ahem-2022-0036

Palabras claveSMAD4 gene, resection, pancreatic cancer, recurrence, overall survival

© 2022 Hui Su et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Fig. 1

Fig. 2

Fig. 3

Fig. 4

Fig. 5

Overview of the reviewed studies

Palabras clave
SMAD4 gene, resection, pancreatic cancer, recurrence, overall survival