The role of pleomorphic adenoma gene-like 2 in gastrointestinal cancer development, progression, and prognosis

Abstract

Numerous previous studies have revealed that pleomorphic adenoma gene-like 2 (PLAGL2) is a transcription factor that is active in cancer progression. The aim of this study was to investigate the role of PLAGL2 in the development, progression and prognosis of gastrointestinal cancer. Immunohistochemical analysis revealed that PLAGL2 was expressed in gastrointestinal tumors and adjacent normal tissues. The expression of PLAGL2 was significantly higher in 225 colorectal cancer tissues than in 66 adjacent non-tumor tissues (P = 0.037). However, expression was not significantly different between 286 gastric tumors and 57 adjacent non-tumor tissues (P = 0.352). Moreover, the PLAGL2 expression level significantly correlated with the depth of tumor invasion in colorectal cancer (P = 0.030). However, the PLAGL2 expression level significantly correlated with tumor size in gastric cancer (P = 0.046). Furthermore, we performed survival analyses and found that neither higher nor lower PLAGL2 expression was a prognostic factor in gastrointestinal cancer. Our findings indicate that PALGL2 serves as a tumor oncoprotein in the development and progression of colorectal cancer. However, the role of this protein in the development, progression and prognosis of gastric cancer is uncertain. Further investigation into the molecular mechanisms of PLAGL2 activity in gastrointestinal cancer is warranted.

Introduction

Gastrointestinal cancer is one of the most common malignancies worldwide. In recent times, gastrointestinal cancer incidence rates have increased year over year [1,2]. As is the case for other cancers, the development of gastrointestinal cancer originates from disturbances in the cellular functions of self-renewal, differentiation, survival and proliferation [3]. These disturbances are frequently driven by genetic abnormalities in cancer cells. In the recent studies, the pleomorphic adenoma gene (PLAG)-family proteins (e.g., PLAG1, PALGL1 and PLAGL2) have been shown to play an important role in the regulation of a wide variety of physiological processes in mammals, including cell proliferation and tissue-specific gene regulation. These proteins may also play a role in complex pathologies such as tumorigenicity [4,5].

Pleomorphic Adenoma Gene-like 2 (PLAGL2) is a zinc-finger transcription factor located in the nucleus [4,6-10] that was initially identified through sequence homology to its family member PLAG1, a proto-oncogene frequently rearranged and overexpressed in pleomorphic salivarygland adenomas, lipoblastomas, uterine leiomyomas, leiomyosarcomas, and smooth tumors [9,11-15]. PLAGL2 was initially found in mouse cell lines and fetal human tissues [8,11]. But soon afterwards, other studies revealed that PLAGL2 is ubiquitously expressed in all adult human tissues [10,16]. Like PLAG1, accumulating evidence indicated that PLAGL2 plays an important role in cancer progression [12,17-20]. Hensen et al. showed that overexpressed PLAGL2 causes neoplastic transformation in NIH3T3 cells [12]. Moreover, PLALG2 overexpression triggers the development of acute myeloid leukemia (AML) in the mouse, and the expression of PLAGL2 was elevated in 20% of AML samples [17]. In human malignant gliomas, Zheng et al. used integrated genomic and biological analyses to determine that the PLAGL2 gene was targeted for amplification and high expression [18]. Recent studies have shown that induced PLAGL2 double-transgenic mice developed lung adenocarcinoma, and the PLAGL2 expression level was elevated in human lung tumors [19]. Furthermore, Martin et al. demonstrated in a study of 42 primary CRC tumors and 37 CRC cell lines that PLAGL2 may be an oncogene relevant to CRC pathogenesis [20]. PLAGL2 expression has also exhibited oncogenic characteristics in functional studies of colorectal cancer cases [18]. Although many previous studies have focused on the expression or mechanisms of PLAGL2 in cancer progression, the role of PLAGL2 in the development, progression and prognosis of gastrointestinal cancer remains unclear. Therefore, the goal of this study was to investigate the expression of PLAGL2 in a large number of gastrointestinal cases and to analyze the relationship between PLAGL2 and the clinical characteristics of patients with a primary focus on prognosis.

Materials and methods

Patients and tissue samples

A total of 511 formalin-fixed and paraffin-embedded gastrointestinal tumor samples and 123 corresponding normal samples were obtained for this study. All of the cancer patients underwent gastrointestinal cancer resection with standard lymph node dissection at the Department of Surgical Oncology, First Hospital of China Medical University between 1998 and 2004. None of the patients had received chemotherapy or radiotherapy before the surgical procedure. We received written informed consent from all patients, and the study was approved by the ethics committee of the China Medical University. The detailed postoperative pathological diagnosis reports were gained and included age, gender, tumor location, size, differentiation status, growth pattern, invasion depth, lymph node metastasis, lymphatic invasion and TNM stage. We used the TNM classification system for gastrointestinal carcinoma from the 7th American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging manual [21]. The criteria for tumor growth patterns in gastric cancers were from the Japanese classification of gastric carcinoma, 3rd English edition [22]. Our experimental cohort contained 225 colorectal cancer patients and 286 gastric cancer patients. The characteristics of all patients are summarized in Tables 1 and 2. All patients were followed up via telephone inquiry or questionnaires, and the follow-up time ranged from 2 to 71 months (median 47 months) for the colorectal cases and from 1 to 149 months (median 62 months) for the 286 gastric cases.

Table 1.

Clinicopathological characteristics of 225 colorectal cancer patients

Variable	n
Age at surgery (years)
Mean	63
Range	32-88
Gender
Male	126
Female	99
Tumor size (cm)
Mean	5.5
Range	1.0-16.0
Tumor location
Rectum	136
Colon	89
Differentiation status
Well	123
Moderately	45
Poorly	57
T stage
T1/T2	70
T3/T4	155
Lymph node metastasis
Negative	138
Positive	87
M stage
Negative	219
Positive	6
Lymphatic invasion
Negative	206
Positive	19
Tumor stage
I	58
IIa, IIb, IIc	79
IIIa, IIIb, IIIc	82
IVa, IVb	6
Prognosis
Alive	155
Dead, all causes†	70

^†Dead, all causes, included death related to colorectal cancer (149), death unrelated to colorectal cancer (2), and information unavailable (4).

Table 2.

Clinicopathological characteristics of 286 gastric cancer patients

Variable	n	Variable	n
Age at surgery (years)		T stage
Mean	58	T1	25
Range	26-81	T2	45
Gender		T3	154
Male	211	T4	62
Female	75	Lymph node metastasis
Tumour size (cm)		Negative	74
Mean	5.1	Positive	212
Range	0.5-15.0	Lymphatic invasion
Tumor location1		Negative	208
Upper	31	Positive	78
Middle	46	General classification3
Lower	208	Borrmann 1	3
Differentiation status		Borrmann 2	31
Well differentiation	29	Borrmann 3	202
Moderately differentiation	41	Borrmann 4	24
Poorly differentiation	208	Tumor stage
Undifferentiation	8	I/II	97
Growth pattern2		III/IV	189
Expanding	67	Prognosis
Intermediate	90	Alive	141
Infiltrative	122	Dead, all causes†	145

¹one case didn’t report the tumor location.

²seven cases didn’t report the growth pattern.

³Twenty-sixe patients were diagnosed with early gastric cancer.

^†Dead, all causes, included death related to gastric cancer (120), death unrelated to gastric cancer (12), and information unavailable (13).

Immunohistochemistry

Four-μm-thick sections cut from formalin-fixed, paraffin-embedded tissue blocks were deparaffinized with xylene and rehydrated using a graduated ethanol series. The tissue sections were incubated with 0.3% hydrogen peroxide (H₂O₂) solution for 12 min to block endogenous peroxidase activity. The sections were incubated in boiling citric-acid buffer (pH 6.0) for antigen retrieval in a steam pressure cooker. Then samples were incubated in goat serum at room temperature for 30 min. After blocking for non-specific antibody binding, the sections were separately incubated overnight at 4°C with an anti-PLAGL2 polyclonal antibody at a 1:200 dilution (ab121239, Abcam, Cambridge, USA). The secondary and tertiary antibodies were added sequentially at room temperature and incubated for 15 min each. Immunohistochemical staining was conducted using a Histostain-Plus kit (Zymed Laboratories Inc., San Francisco, CA, USA) with diaminobenzidine (DAB) as the chromogen. Sections were then counterstained with hematoxylin. Negative control staining was performed by substituting non-immune rabbit serum and phosphate buffered saline for the primary antibodies.

Evaluation of immunohistochemical staining results

Two pathologists who were blinded to patient outcomes independently interpreted the immunostaining results using a semi-quantitative scoring system. Immunostaining reactions were evaluated by staining intensity (0, no staining; 1, weak straining; 2, moderate straining; and 3, strong straining) and the percentage of stained cells (0, ≤5%; 1, 5-25%; 2, 25-50%; 3, 50-75%; and 4, ≥75%). Then, the percentage of positive cells and the staining intensity were multiplied to generate the immunoreactivity score (IS) for each case [23]. If there were discrepancies in the IS as determined by the two pathologists, specimens were rescored until a consensus was reached. All cases were summarized into two groups according to the IS. In the evaluation of PLAGL2, high expression was defined as detectable immunoreactivity in the nucleus and an IS ≥2 as determined by an ROC curve.

Statistics

PLAGL2 expression and clinicopathological parameters were investigated using the appropriate non-parametric tests (Chi-squared test, paired samples t-test and Spearman’s correlation test). Univariate survival analysis was performed using the Kaplan-Meier method, and differences between the groups were analyzed using the log-rank test. The multivariate Cox regression model of backward stepwise method was used to detect the independent predictors of survival. Two-tailed P values less than 0.05 were considered statistically significant. All statistical analyses were performed using SPSS software (version 19.0; SPSS for Windows, Chicago, IL, USA).

Results

Expression of PLAGL2 in gastrointestinal cancers

As is shown in Figures 1 and 2, PLAGL2 expression was predominantly nuclear with some expression also appearing in the cytoplasm in both cancer and normal tissue. The level of PLAGL2 expression in colorectal cancers was significantly higher than in adjacent non-tumor tissue (IS, 8.83 ± 3.824 versus 6.42 ± 4.445, respectively, P = 0.037). Furthermore, among the 66 paired colorectal samples, PLAGL2 expression was significantly higher in tumors than in adjacent non-tumor tissues (IS, 9.08 ± 3.718 versus 6.42 ± 4.445, P<0.001) (Table 3). In gastric cancer cases, PLAGL2 expression was not significantly difference between the gastric cancers and the adjacent non-tumor tissues (IS, 7.88 ± 3.921 versus 6.70 ± 4.183, respectively, P = 0.352). Moreover, there was no difference in the 57 paired gastric samples (IS, 7.95 ± 4.385 versus 6.70 ± 4.183, P = 0.150) (Table 3). In our experiments, 93.8% (211/225) of colorectal cancer cases showed high PLAGL2 expression and 92.9% (263/283) of gastric cancer cases displayed high expression.

Figure 1.

Immunohistochemical staining for PLAGL2 in colorectal cancer tissue and non-tumor adjacent tissue. A. Non-tumor adjacent tissue (no stain). B. Colorectal cancer tissue (weak). C. Colorectal cancer tissue (moderate). D. Colorectal cancer tissue (strong). Magnification ×400

Figure 2.

Immunohistochemical staining for PLAGL2 in gastric cancer tissue and non-tumor adjacent tissue. A. Non-tumor adjacent tissue (no stain). B. Gastric cancer tissue (weak). C. Gastric cancer tissue (moderate). D. Gastric cancer tissue (strong). Magnification ×400.

Table 3.

Normal-cancer paired sample comparisons (t-test)

Variables	No.	IS Mean ± SD	P-value
PLAGL2 in colorectal samples
Normal	66	6.42 ± 4.445	<0.001*
Cancer	66	9.08 ± 3.718
PLAGL2 in gastric samples
Normal	57	6.70 ± 4.183	0.150
Cancer	57	7.95 ± 4.385

^*Indicated statistical significance (P<0.05).

Correlation between PLAGL2 expression and clinicopathological characteristics of gastrointestinal cancers and survival analysis

We utilized chi-squared analysis to evaluate the relationship between PLAGL2 expression and various clinicopathological parameters in colorectal and gastric cancers. In the colorectal cancer cases, the PLAGL2 expression level was significantly correlated with the depth of tumor invasion (pT stage, P = 0.030) (Table 4). However, our findings revealed no significant correlation between PLAGL2 expression and tumor size, location, histological type, lymph node metastasis, lymphatic invasion, M stage or tumor stage (Table 4). In the gastric cancer cases, the PLAGL2 expression level significantly correlated with the tumor size (P = 0.046) (Table 5), and there was no significant correlation between PLAGL2 expression and tumor location, histological grade, growth pattern, T stage, N stage, lymphatic invasion, general classification or tumor stage (Table 5).

Table 4.

Statistical results of relationships between PLAGL2 expression and various clinicopathologic characteristics in colorectal cancer

Variables	Total	Low (%)	High (%)	P-value
	225	14	211
Age at surgery (years)
≤60	79	5	74	0.961
>60	146	9	137
Gender
Male	126	10	116	0.230
Female	99	4	95
Pathophysiologic features
Tumor size (cm)
≤5	116	8	108	0.666
>5	109	6	103
Tumor location
Rectum	136	9	127	0.761
Colon	89	5	84
Histological type
WD/MD	168	12	156	0.326
PD	57	2	55
T stage
T1/2	70	8	62	0.030*
T3/4	155	6	149
Lymph node metastasis
Negative	138	7	131	0.369
Positive	87	7	80
M stage
M0	219	14	205	0.552
M1	6	0	6
Lymphatic invasion
Negative	206	13	193	0.856
Positive	19	1	18
Tumor stage
I	58	5	53	0.312
IIa, IIb, IIc	79	2	77
IIIa, IIIb, IIIc	82	7	75
IVa, IVb	6	0	6

^*Indicated statistical significance (P<0.05).

Table 5.

Statistical results of relationships between PLAGL2 expression and various clinicopathologic characteristics in gastric cancer

Variables	Total	Low (%)	High (%)	P-value
	286	23	263
Age at surgery (years)
≤60	157	9	148	0.113
>60	129	14	115
Gender
Male	211	20	191	0.134
Female	75	3	72
Pathophysiologic features
Tumor size (cm)
≤5	168	9	159	0.046*
>5	118	14	104
Tumor location1
Upper	31	5	26	0.087
Middle	46	1	45
Lower	208	17	191
Histological grade
Well differentiation	29	2	27	0.293
Moderate differentiation	41	2	39
Poor differentiation	208	17	191
Undifferentiation	8	2	6
Growth pattern2
Expanding	67	4	63	0.317
Intermediate	90	5	85
infiltrative	122	13	109
T stage
T1	25	0	25	0.119
T2	45	5	40
T3	154	16	138
T4	62	2	60
N stage
N0	74	4	70	0.243
N1	36	4	32
N2	71	3	68
N3	105	12	93
M stage
Negative	203	14	189	0.265
Positive	83	9	74
Lymphatic invasion
Negative	208	19	189	0.267
Positive	78	4	74
General classification3
Borrmann 1	3	1	2	0.137
Borrmann 2	31	0	31
Borrmann 3	202	20	182
Borrmann 4	24	2	22
Tumor stage
I/II	97	6	91	0.408
III/IV	189	17	172

¹one case didn’t report the tumor location.

²seven cases didn’t report the growth pattern.

³Twenty-sixe patients were diagnosed with early gastric cancer.

^*Indicated statistical significance (P<0.05).

According to univariate survival analysis, T stage (P<0.001), lymph node metastasis (P<0.001), M stage (P<0.001), lymphatic invasion (P<0.001), and tumor stage (P<0.001) were all significant prognostic factors (Table 6) for colorectal cancer. According to Cox multivariate analysis, lymphatic invasion (P = 0.005) and tumor stage (P = 0.008) remained significant prognostic factors (Table 6). In survival analysis, higher PLAGL2 expression was not a prognostic factor (P = 0.475) (Figure 3A). In gastric cancers, tumor size (P<0.001), T stage (P<0.001), N stage (P<0.001), M stage (P<0.001), lymphatic invasion (P = 0.001), general classification (P<0.001), and tumor stage (P<0.001) were all significant prognostic factors, according to univariate survival analysis (Table 7). According to Cox multivariate analysis, T stage (P = 0.002), N stage (P<0.001), and M stage (P = 0.039) remained significant prognostic factors (Table 7). In survival analysis, higher PLAGL2 expression was still not prognostic for gastric cancers (P = 0.137) (Figure 3B).

Table 6.

Survival analysis in colorectal cancer

	Univariate			Multivariate
Variable	Total (%)	5 years (%)	P-value	RR	95% CI	P-value
Age at surgery (years)
≤60	79	68.7	0.413
>60	146	70.4
Gender
Male	126	73.2	0.470
Female	99	68.1
Pathophysiologic features
Tumor size (cm)
≤5	116	70.0	0.749
>5	109	70.8
Tumor location
Rectum	136	74.8	0.438
Colon	89	68.3
Histological grade
WD/MD	168	75.5	0.270
PD	57	62.8
T stage
T1/2	70	82.5	<0.001*	0.659	0.286-1.519	0.328
T3/4	155	65.7
Lymph node metastasis
Negative	138	89.9	<0.001*	4.738	0.501-44.789	0.175
Positive	87	39.7
M stage
M0	219	75.3	<0.001*	0.484	0.171-1.366	0.171
M1	6	16.7
Lymphatic invasion
Negative	206	76.2	<0.001*	0.377	0.192-0.740	0.005*
Positive	19	31.6
Tumor stage
I	58	92.1	<0.001*	0.042	0.004-0.436	0.008*
IIa, IIb, IIc	79	80.9
IIIa, IIIb, IIIc	82	40.9
IVa, IVb	6	16.7
PLAGL2 expression
Low	14	76.2	0.475
High	211	73.4

^*Indicated statistical significance (P<0.05).

Figure 3.

Survival analysis in patients with colorectal cancer and gastric cancer. A. PLAGL2 expression was no associated with overall survival in colorectal cancer patients. B. PLAGL2 expression was no associated with overall survival in gastric cancer patients.

Table 7.

Survival analysis in gastric cancer

	Univariate			Multivariate
Variable	Total (%)	5 years (%)	P-value	RR	95% CI	P-value
Age at surgery (years)
≤60	157	61.8	0.428
>60	129	54.8
Gender
Male	211	72.4	0.612
Female	75	46.7
Pathophysiologic features
Tumor size (cm)
≤5	168	64.8	<0.001*	0.983	0.691-1.400	0.925
>5	118	49.7
Tumor location1
Upper	31	33.5	0.134
Middle	46	43.5
Lower	208	71.2
Histological grade
Well/Moderate differentiation	70	49.3	0.634
Poor differentiation	216	73.1
Growth pattern2
Expanding	67	58.2	0.287
Intermediate	90	48.9
infiltrative	122	51.3
T stage
T1	25	70.0	<0.001*	0.555	0.380-0.811	0.002*
T2	45	77.8
T3	154	61.5
T4	62	21.0
N stage
N0	74	85.1	<0.001*	0.449	0.301-0.671	<0.001*
N1	36	71.2
N2	71	46.5
N3a/3b	105	42.9
M stage
Negative	203	71.8	<0.001*	0.667	0.453-0.981	0.039*
Positive	83	32.4
Lymphatic invasion
Negative	208	71.5	0.001*	0.798	0.556-1.145	0.221
Positive	78	35.9
General classification3
Borrmann 1	3	66.7	<0.001*	0.654	0.393-1.089	0.102
Borrmann 2	31	70.8
Borrmann 3	202	70.7
Borrmann 4	24	20.8
Tumor stage
I/II	97	88.5	<0.001*	0.456	0.182-1.143	0.094
III/IV	189	69.8
PLAGL2 expression
Low	23	39.1	0.137
High	263	77.5

¹one case didn’t report the tumor location.

²seven cases didn’t report the growth pattern.

³Twenty-sixe patients were diagnosed with early gastric cancer.

^*Indicated statistical significance (P<0.05).

Discussion

In this study, we used immunohistochemistry to investigate the expression of PLAGL2 in 511 gastrointestinal cancer patients. According to previous studies and the manufacturer’s instructions, PLAGL2 immunostaining was predominantly nuclear, and we also found that PLAGL2 was expressed in the cytoplasm. This pattern of expression may be caused by the use of polyclonal antibodies. Goldenberg et al. used immunohistochemistry to demonstrate that there was no PLAGL2 expression in human colon cancer [24]. Conversely, we found substantial PLAGL2 expression in human gastrointestinal tissues, including tumor and normal tissues. The level of PLAGL2 expression may be different in different cancers, however. In recent studies, aberrant PLAGL2 expression has been observed in acute myeloid leukemia (AML), glioblastomas (GBM), and lung adenocarcinoma [17,18,24-27]. In the present study, PLAGL2 expression in colorectal cancers was significantly higher than in adjacent non-tumor tissues. However, there was no significant difference between the expression of PLAGL2 in gastric cancers and adjacent non-tumor tissues. Also, we found that higher expression levels of PLAGL2 significantly correlated with the depth of tumor invasion. This result was consistent with the observation that high PLAGL2 expression in GBM promoted glioma cell invasion [18,24]. Although PLAGL2 could inhibit cell differentiation in GBM, we found that the expression of PLAGL2 did not correlate with the degree of differentiation. Thus far, there has been no reported research concerning that the role that PLAGL2 plays in gastric tissues. In this study, we demonstrated that PLAGL2 expression was widespread in the gastric tissues, and elevated expression of PLAGL2 significantly correlated with tumor size in gastric cancers. Moreover, we believe that PLAGL2 expression is likely to be influenced by tissue specificity, the patient population and environment, and sample size. These issues need to be resolved by larger multicenter studies in the future.

To date, few studies have evaluated the relationship between PLAGL2 and prognosis in cancer. Recently, Yang et al. have reported that female patients with low PLAGL2 expression at an early stage of disease had better prognosis for survival from lung adenocarcinoma, while no correlation was observed for male patients [19]. In our present study of gastrointestinal cancer, PLAGL2 expression was not a prognostic factor in survival analysis.

Currently, the mechanism of action for PLAGL2 in gastrointestinal tissues, and especially in colorectal cancers, remains unknown. In the NIH3T3 cells, Hensen et al. have suggested that PLAGL2’s oncogenic capacity is mediated by the activation of the insulin-like growth factor-II (IGF-II) mitogenic pathway via IGF-I-R, which activates the Ras/Raf mitogen-activated protein kinase pathway and restarts the developmental program with a loss of differentiation [12,15]. Moreover, PLAGL2 increased proliferation by promoting the G1 to S transition and increasing cell renewal in a manner that induces acute myeloid leukemia in cooperation with Cbfb-MYH11 [17]. In recent studies of glioblastoma, PLAGL2 expression suppressed cellular differentiation and promoted cellular capacity for self-renewal by activating the Wnt/β-catenin pathway and cell-to-cell fusion that permits the transfer of genetic information between tumor and stromal cells [18,24,27]. Another study has reported that PLAGL2 might program cell growth and contribute to the development of lung adenocarcinoma by modifying the bNip3 gene [19]. In addition, PLAGL2 regulation of the activation of p53 and its family members may represent another mechanism of cellular activation [13,28]. On the one hand, PLAGL2 serves as an oncoprotein through interactions with Pirh2 dimers that stabilize Pirh2 by inhibiting proteasome-mediated Pirh2 degradation and promoting the degradation of p53 in HKE293 cells [13]. On the other hand, PLAGL2 serves as a tumor suppressor by inducing cell-cycle block and apoptosis via the regulation of p73, a p53 family member in human promonocytic U937 cells [28]. Clearly, the mechanism of PLAGL2 action in colorectal cancers is complex and requires further study.

Although we didn’t find any differences in PLAGL2 expression between gastric cancers and adjacent non-tumor tissue, we did observe expression in gastric tissues in our study. In previous studies, PLAGL2 has been identified as an oxidative stress-responsive regulator that activates the SP-C promoter during lung development under hypoxia [7,16,29]. Yang et al. found that PLAGL2 expression significant resulted in functional and structural defects in the respiratory system by mediating airway epithelial cell injury and apoptosis [7]. These issues prompted us to determine the role of PLAGL2 in gastric tissues.

In addition, the activity of PLAGL2 protein requires various modulatory factors. In the mouse macrophage cell line RAW264.7, PLAGL2 was induced when cells were incubated under hypoxic conditions or with desferrioxamine [8]. Zheng et al. found that sumoylation and acetylation played opposite roles in the transactivation of PLAGL2 at the same lysine residues [6]. They showed that the transcriptional activity of PLAGL2 was negatively regulated by sumoylation. They also revealed that PLAGL2 was acetylated and activated by p300 and Tip60, and deacetylated and repressed by HDAC7 [6,9]. Furthermore, PC2, a component of the ARC/Mediator complex, modulated the transactivation of PLAGL2 by binding to its C-terminus [4].

In conclusion, we studied expression of PLAGL2 in gastrointestinal carcinoma and found that PLAGL2 expression in the gastric and colorectal cancer tissues was significantly higher than in adjacent non-tumor tissues. Also, elevated PLAGL2 expression was associated with the depth of tumor invasion in colorectal cancer tissues, but the mechanism of PLAGL2 in gastrointestinal is still unknown. Our findings suggest that PLAGL2 should be evaluated as a novel preoperative biomarker to assist in the evaluation of tumor invasion and guide treatment in colorectal cancer.

Disclosure of conflict of interest

None.