Fig. 1
Systematic flow diagram for selection of included studies
Table 1
Overview of the reviewed studies
| Author, Year | Country | Group | No. of patients | Sex (male/female) | Mean tumor size (mm) | Mean age | Lymph nodes metastasis (P/N) | Margin status (R0/R1) | Differentiation: Well and moderate / Pool | Lymphatic invasion (P/N) | Vascular invasion (P/N) | TNM stage I and II / III and IV |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Oshima M 2013 [15] | Japan | SMAD4+ SMAD4− | 106 | 62/44 | 26.5 33.9 | 68 | 22/20 50/14 | 31/11 44/20 | 36/6 55/9 | 28/14 54/10 | 35/7 57/7 | ---- |
| Yamada S 2015 [16] | Japan | SMAD4+ SMAD4− | 174 | 44/26 59/45 | ---- | 63.7 | 48/22 84/20 | ---- | ---- | 54/16 94/10 | 34/36 64/40 | ---- |
| Herman JM 2018 [17] | USA | SMAD4+ SMAD4− | 145 | 36/21 45/43 | 30 30 | 63 62 | 8/49 18/80 | 33/24 55/33 | ---- | ---- | ---- | 34/23 56/32 |
| Tascilar M 2001 [18] | USA | SMAD4+ SMAD4− | 253 | 61/50 78/60 | ---- | 71/40 85/53 | 79/32 89/48 | ---- | ---- | 8/9 | 26/85 33/105 | |
| Biankin AV 2002 [19] | Australia | SMAD4+ SMAD4− | 348 | 190/158 | ---- | 64 | ---- | ---- | 78/51 | ---- | ---- | ---- |
| Xu JZ 2019 [20] | China | SMAD4+ SMAD4− | 237 | 30/39 102/66 | ---- | ---- | 33/36 75/93 | ---- | 54/15 111/57 | ---- | 9/60 33/135 | 57/12 129/39 |
| Ottenhof NA 2012 [21] | The Netherlands | SMAD4+ SMAD4− | 78 | 35/43 | ---- | ---- | ---- | 52/26 | 56/21 | 54/23 | ---- | 20/58 |
| Shen J 2019 [22] | China | SMAD4+ SMAD4− | 247 | 120/61 39/27 | ---- | ---- | 95/86 32/34 | 137/44 45/21 | ---- | ---- | 51/130 15/51 | ---- |
| Toga T 2004 [23] | Japan | SMAD4+ SMAD4− | 88 | 6/7 37/38 | ---- | ---- | 9/4 69/6 | ---- | 11/2 71/4 | ---- | ---- | 5/8 12/63 |
| Bachet JB 2012 [24] | France | SMAD4+ SMAD4− | 471 | 256/215 | 30 | 63 | 351/120 | 377/89 | 390/67 | ---- | ---- | 471/0 |
| Winter JM 2013 [25] | USA | SMAD4+ SMAD4− | 127 | 256/215 | ---- | ---- | ---- | ---- | ---- | ---- | ---- | ---- |
| Shin SH 2017 [26] | Korea | SMAD4+ SMAD4− | 641 | 374/267 | ---- | ---- | ---- | 548/93 | 543/81 | ---- | ---- | ---- |
Table 2
Overview of the reviewed studies
| 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 | 44/26 59/45 | IHC | Santa 1:100 | >0 | 7 |
| Herman JM 2018 [17] | USA | SMAD4+ SMAD4− | PDAC | 36/21 45/43 | IHC | ---- | >0 | 7 |
| Tascilar M 2001 [18] | USA | SMAD4+ SMAD4− | PAC | 61/50 78/60 | 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 | 30/39 102/66 | 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 | 6/7 37/38 | 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 |
Fig. 2
Forest plot showing the association between the loss of SMAD4 expression and OS in PC using multivariate analyses
Fig. 3
Forest plot showing the association between the loss of SMAD4 expression and recurrence in PC. A. Local recurrence. B. Distant recurrence
Fig. 4
Begg's funnel plot and Egger's funnel plot for all studies included in this meta-analysis
Fig. 5
Effect of individual studies on the pooled HR for OS