Decreased expression of LKB1 predicts poor prognosis in pancreatic neuroendocrine tumor patients undergoing curative resection

Figures & data

Figure 1 LKB1 mRNA and protein levels in pNET tissues and paired normal tissues.

Notes: (A) The mRNA levels of LKB1 were examined via qRT-PCR in 24 pairs of pNET tissues and corresponding nontumorous tissues. GAPDH was used as an internal control. Relative gene expression was determined using the comparative delta-delta CT method, and data are presented as ΔΔCt (P<0.001, paired Student’s t-test). (B) Representative Western blot images of LKB1 protein level in pairs of pNET tissues (T) and corresponding nontumorous tissues (N).
Abbreviations: LKB1, liver kinase B1; pNET, pancreatic neuroendocrine tumor; qRT-PCR, quantitative real-time reverse-transcription polymerase chain reaction.

Figure 2 Immunohistochemical staining results of LKB1 expression in pNET tissue samples.

Notes: (A–E) Representative images of LKB1 expression in pNET tissues. (A) Tissue with diffused strong LKB1 staining; (B) tissue with strong LKB1 staining in more than 50% tumor area; (C) tissue with strong LKB1 staining in less than 50% tumor area; (D) tissue with disused weak LKB1 staining; (E) tissue with weak LKB1 staining in less than 50% tumor area; and (F) a sketch illuminating the classification method of LKB1 immunostaining in pNET tissues. Magnification for these images is 100×.
Abbreviations: LKB1, liver kinase B1; pNET, pancreatic neuroendocrine tumor.

Table 1 Correlation between LKB1 expression and clinicopathological features in patients with pNET

Variables	Patients (n=71)	LKB1 expression levels		P-valueb
		High (n=33)	Low or negative (n=38)
Age, years (mean ± SD)	45.2±17.5	40.3±15.1	49.11±17.6	0.042
Gender				0.088
Female	29	17	12
Male	42	16	26
Tumor size, cm (mean ± SD)	3.3±2.1	2.70±1.73	3.75±2.33	0.307
Median (upper and lower quartiles)		2 (0.4–7)	3.45 (0.8–9)
Function				0.085
Functional	31	18	13
Non-functional	40	15	25
Location				0.925
Head/uncinate	34	16	18
Body and/or tail	37	17	20
Margin status				0.348
R0	70	33	37
R1	1	0	1
Differentiation				0.072
Well/moderate	64	32	32
Poor	7	1	6
Ki-67 index, %				0.004
≤2	39	25	14
3–20	26	7	19
>20	6	1	5
Mitotic count, per 10 HPF				0.001
<2	38	28	10
2–20	25	4	21
>20	8	1	7
G gradea				0.001
G1	31	24	7
G2	30	7	23
G3	10	2	8

Note:

a The histologic grade was classified according to WHO 2010 classification system;

b t-test for continuous variables and chi-square test for categorical variables.

Abbreviations: LKB1, liver kinase B1; pNET, pancreatic neuroendocrine tumor; HPF, high power field; WHO, World Health Organization.

Figure 3 Correlation between LKB1 and survival outcomes tested by Kaplan–Meier analysis and log-rank test.

Notes: (A) Patients with low/negative expression of LKB1 had a significantly decreased OS than those with high expression (log-rank test, P=0.0021). (B) Patients with low/negative expression of LKB1 had a significantly decreased DFS than those with high expression (log-rank test, P=0.009). (C) In patients with non-functional pancreatic neuroendocrine tumors (NF-pNETs), decreased LKB1 expression was associated with poor OS (log-rank test, P=0.121). (D) In patients with NF-pNETs, decreased LKB1 expression was associated with significantly shorter DFS (log-rank test, P=0.036).
Abbreviations: LKB1, liver kinase B1; OS, overall survival; DFS, disease-free survival.