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. 2016 Apr 19;7(16):22911-27.
doi: 10.18632/oncotarget.8094.

Decreased MALL expression negatively impacts colorectal cancer patient survival

Xiaoliang Wang  1 , Junwei Fan  1 , Fudong Yu  1 , Feifei Cui  1 , Xing Sun  1 , Lin Zhong  1 , Dongwang Yan  1 , Chongzhi Zhou  1 , Guilong Deng  1 , Bin Wang  1 , Xiaosheng Qi  1 , Shuyun Wang  1 , Lei Qu  1 , Biao Deng  1 , Ming Pan  1 , Jian Chen  1 , Yupeng Wang  1 , Guohe Song  1 , Huamei Tang  2 , Zongguang Zhou  3 , Zhihai Peng  1
Affiliations

Decreased MALL expression negatively impacts colorectal cancer patient survival

Xiaoliang Wang et al. Oncotarget. .

Abstract

The aim of the present study was to determine whether MALL expression is associated with colon cancer progression and patient survival. MALL mRNA expression was reduced in the tumor tissues of 70% of the colon cancer patients and 75% of the rectal cancer patients as compared to their normal tissues. MALL protein was also significantly reduced in the tumor tissues of colon cancer patients (P < 0.001). Increased LOH and methylation of MALL was observed in tumor tissues as compared to normal tissues. Reduced MALL expression was associated with vessin invasion, disease recurrence and metastasis or death (P ≤ 0.027). Furthermore, patients with MALL-negative tumors had significantly decreased overall survival (OS) and disease-free survival (DFS) (P < 0.008 and P < 0.011, respectively). Univariate analysis indicated that MALL expression was significantly associated with OS and DFS. Finally, overexpression of MALL suppressed HCT116 and SW480 cell proliferation and inhibited HCT116 migration. MALL may play a role in colorectal cancer progression as suppression of its expression in tumor tissues negatively impacts colorectal cancer patient survival. Further analyses are required to determine if reduced MALL expression is due to LOH and/or methylation.

Keywords: biomarker; colorectal cancer; migration; survival.

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Conflict of interest statement

CONFLICTS OF INTERESTS The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1. MALL expression in normal and cancer tissues by real-time PCR analysis
Analysis of MALL mRNA expression in A. 40 colon cancer tissues and B. 40 rectal cancer tissues with actin as the internal reference. Data are presented as mean ± standard deviation. *P < 0.05 indicates a significant difference between the normal and cancer tissues.
Figure 2
Figure 2. Representative images of MALL immunohistochemistry analysis showing MALL-positive
A. Normal tissue exhibiting strongly positive expression and B. negative control in normal tissue.C.-E. Tumor tissue exhibiting strongly positive C., weakly positive D., and negative E. expression. F. Positive expression in metastatic lymph nodes tissue. Bar = 100 μm; original magnification x400 (x100 for insets).
Figure 3
Figure 3. Colon cancer patient survival relative to MALL expression
A. Overall survival (OS) and B. disease-free survival (DFS) of 203 colon cancer patients were analyzed.
Figure 4
Figure 4. MALL LOH in normal and cancer tissues
MALL LOH in A. colon and B. rectal cancer tissues was determined by real-time PCR using three separate primer sets with PMP as the internal reference. Data are presented as mean ± standard deviation of three independent experiments. *P < 0.05 indicates a significant difference between the normal and cancer tissues.
Figure 5
Figure 5. Levels of MALL mRNA expression after its overexpression
MALL expression in A. SW480 and B. HCT116 cell lines was determined by real-time PCR. Data are presented as mean ± standard deviation of three independent experiments.
Figure 6
Figure 6. The effect of MALL overexpression on colorectal cell proliferation and migration
A. SW480 and B. HCT116 cell proliferation was determined in control, MALL-overexpressing and parental cells using the MTT assay at the indicate time points. C. HCT116 cell migration in control, MALL-overexpressing and parental cells. D. Quantitative analysis of the number of migrating cells in C. Data are presented as mean ± standard deviation of three independent experiments.
Figure 7
Figure 7. MALL suppresses mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling
A. p-ERK and total ERK levels were analyzed Western blot analysis in SW480 and HCT116 cells overexpressing MALL or the vector control. B. Using the BioCarta database of consensusPathDB, we found genes in the ERK signaling pathway. The interaction between genes in the ERK MAPK signaling pathway and the MALL gene were identified using IPA software after removal of unrelated genes.
See this image and copyright information in PMC

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