Prognostic value of minichromosome maintenance mRNA expression in early-stage pancreatic ductal adenocarcinoma patients after pancreaticoduodenectomy

Figures & data

Figure 1 Expression distribution of MCM2–7 in human normal organ tissues.

Notes: Expression distribution box plot of MCM2 (A); MCM3 (B); MCM4 (C); MCM5 (D); MCM6 (E); MCM7 (F).

Abbreviation: MCM, minichromosome maintenance.

Figure 2 Expression distribution of MCM2–7 between PAAD tumor and normal tissues.

Notes: Expression distribution box plot of MCM2 (A); MCM3 (B); MCM4 (C); MCM5 (D); MCM6 (E); MCM7 (F). Expressions of MCM genes were upregulated in PDAC tumor tissues. *P<0.05.

Abbreviations: MCM, minichromosome maintenance; PAAD, pancreatic adenocarcinoma.

Figure 3 Expression distribution of MCM2–7 between PC tumor and normal tissues that was carried out by MERAV. Expressions of MCM genes were upregulated in PC tumor tissues.

Notes: Expression distribution box plot of MCM2 (A); MCM3 (B); MCM4 (C); MCM5 (D); MCM6 (E); MCM7 (F).

Abbreviations: MCM, minichromosome maintenance; MERAV, Metabolic gEne RApid Visualizer; PC, pancreatic cancer.

Figure 4 Coexpression matrix of MCM genes in PDAC tumor tissues and human normal pancreas tissues, and demonstrated that MCM2–7 were strongly positively correlation and coexpressed with each other in both PDAC tumor and normal pancreas tissues.

Notes: (A) Coexpression matrix of MCM genes in PDAC tumor tissues; (B) coexpression matrix of MCM genes in human normal pancreas tissues.

Abbreviations: MCM, minichromosome maintenance; PDAC, pancreatic ductal adenocarcinoma.

Figure 5 Gene expression distribution of MCM genes in different PDAC tumor stages and histologic grades, and ROC curves of MCM genes to distinguish different PDAC histologic grades.

Notes: (A) Gene expression distribution of MCM genes in different PDAC tumor stages; (B) gene expression distribution of MCM genes in different PDAC histologic grades; ROC curves of MCM2 (C), MCM4 (D), MCM7 (E) and MCM2 + MCM7 (F) combination to distinguish different PDAC histological grades. *P<0.05, **P<0.01.

Abbreviations: AUC, area under the curve; MCM, minichromosome maintenance; PDAC, pancreatic ductal adenocarcinoma; ROC, receiver operating characteristic.

Table 1 Correlation between OS and clinicopathologic features of PDAC patientsa

Variables	Events/total (n=112)	MST (days)	HR (95% CI)	Log-rank P-value
Age (years)				0.066
≤60	20/38	593	1
>60	49/74	485	1.636 (0.962–2.780)
Gender				0.523
Female	36/53	511	1
Male	33/59	592	0.855 (0.529–1.382)
Alcohol historyb				0.349
No	25/43	592	1
Yes	38/61	511	1.276 (0.765–2.128)
Pathologic stage				0.943
Stage I	4/8	236	1
Stage II	65/104	518	1.038 (0.375–2.872)
Pathological T				0.466
T1/T2	7/14	498	1
T3	62/98	518	1.340 (0.608–2.949)
Pathological N				0.091
N0	9/21	634	1
N1	60/91	511	1.818 (0.899–3.678)
Pathological M				0.319
M0	31/55	593	1
Mx	38/57	485	1.278 (0.787–2.075)
Histologic grade				0.010
G1/G2	45/80	596	1
G3/G4	24/32	470	1.919 (1.156–3.185)
Radical resectionc				0.009
R1/Rx	29/44	381	1
R0	39/66	603	0.514 (0.310–0.852)
Radiation therapyd				0.029
No	48/70	473	1
Yes	15/30	691	0.527 (0.293–0.947)
Targeted molecular therapye				<0.001
No	24/29	224	1
Yes	41/73	634	0.168 (0.095–0.296)

Notes:

a The data in this table also have been shown in our previous publication²².

b Alcohol history information is unavailable in eight patients;

c Radical resection information is unavailable in two patients.

d Radiation therapy information is unavailable in 12 patients.

e Targeted molecular therapy information is unavailable in ten patients.

Abbreviations: HR, hazard ratio; MST, median survival time; OS, overall survival; PDAC, pancreatic ductal adenocarcinoma.

Table 2 Prognostic values of MCM genes expression in PDAC OS of TCGA cohort

Gene expression	Events/total (n=112)	MST (days)	Crude HR (95% CI)	Crude P-value	Adjusted HR (95% CI)	Adjusted P-valuea
MCM2
Low	31/56	592	1		1
High	38/56	498	1.345 (0.828–2.185)	0.230	1.614 (0.929–2.805)	0.089
MCM3
Low	33/56	592	1		1
High	36/56	517	1.096 (0.679–1.769)	0.708	0.773 (0.453–1.320)	0.346
MCM4
Low	28/56	634	1		1
High	41/56	458	1.990 (1.210–3.272)	0.007	2.409 (1.351–4.294)	0.003
MCM5
Low	32/56	607	1		1
High	37/56	393	1.692 (1.041–2.749)	0.034	1.185 (0.693–2.028)	0.535
MCM6
Low	33/56	511	1		1
High	36/56	568	0.867 (0.534–1.408)	0.564	1.104 (0.645–1.889)	0.718
MCM7
Low	31/56	603	1		1
High	38/56	485	1.456 (0.897–2.364)	0.129	1.183 (0.660–2.119)	0.572

Note:

a Adjusted for histologic grade, radiation therapy, radical resection, and targeted molecular therapy.

Abbreviations: MCM, minichromosome maintenance; MST, median survival time; OS, overall survival; PDAC, pancreatic ductal adenocarcinoma; TCGA, The Cancer Genome Atlas.

Figure 6 Kaplan–Meier survival curves for MCM genes in pancreatic ductal adenocarcinoma of The Cancer Genome Atlas cohort.

Notes: Overall survival stratified by MCM2 (A), MCM3 (B), MCM4 (C), MCM5 (D), MCM6 (E), and MCM7 (F).

Abbreviation: MCM, minichromosome maintenance.

Figure 7 Prognostic value evaluation of MCM4 in patients with PDAC.

Notes: (A) From top to bottom are the expression values of MCM4, patients’ survival status distribution, and the expression heat map of MCM4 in the low- and high-expression groups. (B) Receiver operating characteristic curve for predicting overall survival in PDAC patients by the MCM4.

Abbreviations: MCM, minichromosome maintenance; PDAC, pancreatic ductal adenocarcinoma.

Table 3 Joint effects survival analysis of clinical factors and the MCM4 expression with OS in PDAC patients

Group	MCM4	Variables	Events/total (n=112)	MST (days)	Crude HR (95% CI)	Crude P-value	Adjusted HR (95% CI)	Adjusted P-valuea
Histologic grade
A	Low expression	G1 + G2	20/44	634	1		1
B	Low expression	G3 + G4	8/12	592	1.652 (0.711–3.837)	0.243	1.782 (0.713–4.457)	0.217
C	High expression	G1 + G2	25/36	518	1.830 (0.991–3.380)	0.054	2.146 (1.051–4.383)	0.036
D	High expression	G3 + G4	16/20	278	3.788 (1.893–7.579)	<0.001	5.185 (2.373–11.329)	<0.001
Radiation therapyb
a	Low expression	No	17/31	607	1		1
b	Low expression	Yes	8/19	702	0.686 (0.289–1.626)	0.392	1.403 (0.513–3.836)	0.510
c	High expression	No	31/39	366	2.047 (1.097–3.819)	0.024	2.977 (1.509–5.871)	0.002
d	High expression	Yes	7/11	627	1.010 (0.408–2.497)	0.983	0.657 (1.880–5.378)	0.239
Radical resectionc
I	Low expression	R0	20/41	702	1		1
II	Low expression	R1/Rx	7/13	592	1.732 (0.708–4.232)	0.229	1.457 (0.555–3.826)	0.445
III	High expression	R0	19/25	517	1.775 (0.924–3.408)	0.085	2.413 (1.162–5.014)	0.018
IV	High expression	R1/Rx	22/31	308	2.975 (1.560–5.673)	0.001	3.498 (1.724–7.101)	0.01
Targeted molecular therapyd
i	Low expression	No	8/13	467	1		1
ii	Low expression	Yes	18/37	702	0.239 (0.098–0.583)	0.002	0.204 (0.076–0.547)	0.002
iii	High expression	No	16/16	145	5.036 (2.007–12.638)	0.001	4.303 (1.625–11.399)	0.003
iv	High expression	Yes	23/36	603	0.411 (0.180–0.940)	0.035	0.357 (0.148–0.859)	0.021

Notes:

a Adjusted for histologic grade, radiation therapy, radical resection, and targeted molecular therapy.

b Radiation therapy information is unavailable in 12 patients;

c radical resection information is unavailable in two patients.

d Targeted molecular therapy information is unavailable in 10 patients.

Abbreviations: HR, hazard ratio; MST, median survival time; OS, overall survival; PDAC, pancreatic ductal adenocarcinoma.

Figure 8 The relationship between MCM4 and clinical information.

Notes: (A) Stratified analysis of association between MCM4 and overall survival in pancreatic ductal adenocarcinoma. (B) Nomogram for predicting the 1-, 2-, and 3-year event (death) with MCM4 and clinical information.

Abbreviation: MCM, minichromosome maintenance.

Figure 9 Joint effects analysis of overall survival stratified by MCM4 and pancreatic ductal adenocarcinoma clinical parameters.

Notes: Joint effects analysis stratified by MCM4 and following clinical parameters: Histologic grade (A), radiation therapy (B), radical resection (C), and targeted molecular therapy (D).

Abbreviation: MCM, minichromosome maintenance.

Figure 10 GSEA results of MCM4 in PDAC patients.

Notes: (A–F) GSEA results of c2 reference gene sets for high MCM4 expression groups; (G–L) GSEA results of c5 reference gene sets for high MCM4 expression groups.

Abbreviations: ES, enrichment score; FDR, false discovery rate; GSEA, gene set enrichment analysis; MCM, minichromosome maintenance; NES, normalized enrichment score; PDAC, pancreatic ductal adenocarcinoma.

LiaoXHuangKHuangRGenome-scale analysis to identify prognostic markers in patients with early-stage pancreatic ductal adenocarcinoma after pancreaticoduodenectomyOnco Targets Ther2017104493450628979141

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