MAL2 expression predicts distant metastasis and short survival in pancreatic cancer

Eguchi, Daiki; Ohuchida, Kenoki; Kozono, Shingo; Ikenaga, Naoki; Shindo, Koji; Chen, Lin; Fujiwara, Kenji; Akagawa, Shinobu; Ohtsuka, Takao; Takahata, Shunichi; Shoji, Tetsuo; Mizumoto, Kazuhiro; Tanaka, Masao

doi:10.1016/j.surg.2013.03.010

Cited by 34 publications

(32 citation statements)

References 31 publications

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“…The frequent overexpression of MAL2 in CRC primary tumor tissues and its low expression in non-cancerouslesions, implieda potential application for MAL2 in tumor monitoring and detection, particularly in high-grade carcinoma, which was consistent with the previous study of MAL2 in breast and ovarian cancer[11,18–20]. It has been shown that highly metastatic cells demonstrates the overexpression of MAL2 and high expression of MAL2 is associated with a lesser survival of postoperative patients and a high rate of distant metastasis in pancreatic cancer [45]. However, MAL2 expression in lymph node and liver metastasis tissues showed no significant elevation compared with primary carcinoma in our study, suggesting that MAL2 might not be directly correlated with tumor metastasis through lymph node and liver.…”

Section: Discussionsupporting

confidence: 88%

The four-transmembrane protein MAL2 and tumor protein D52 (TPD52) are highly expressed in colorectal cancer and correlated with poor prognosis

et al. 2017

PLoS ONE

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The four-transmembrane protein MAL2 and tumor protein D52 (TPD52) have been shown to be involved in tumorigenesis of various cancers. However, their roles in colorectal cancer (CRC) remain unclear. In this study, we explored the expressions of MAL2 and TPD52 in tumor specimens resected from 123 CRC patients and the prognostic values of the two proteins in CRC. Immunohistochemical analyses showed that MAL2 (P<0.001) and TPD52 (P<0.001) were significantly highly expressed in primary carcinoma tissues compared with adjacent non-cancerous mucosa tissues. And TPD52 exhibited frequent overexpression in liver metastasis tissues relative to primary carcinoma tissues (P = 0.042), while MAL2 in lymphnode and liver metastasis tissues showed no significant elevation. Real-time quantitative PCR (RT-qPCR) showed the identical results. Correlation analyses by Pearson’s chi-square test demonstrated that MAL2 in tumors was positively correlated with tumor status (pathological assessment of regional lymph nodes (pN, P = 0.024)), and clinic stage (P = 0.017). Additionally, the expression of TPD52 was detected under the same condition and was shown to be positively correlated withtumor status (pathological assessment of the primary tumor (pT, P = 0.035), distant metastasis (pM, P = 0.001)) and CRC clinicopathology(P = 0.024). Kaplan-Meier survival curves indicated that positive MAL2 (P<0.001) and TPD52 (P<0.001) expressions were associated with poor overall survival (OS) in CRC patients. Multivariate analysis showed that MAL2 and TPD52 expression was an independent prognostic factor for reduced OS of CRC patients. Moreover, overexpression of TPD52 in CRC SW480 cells showed an increased cell migration (P = 0.023) and invasion (P = 0.012) through inducing occurrence of epithelial-mesenchymal transition (EMT) and activating focal adhesion kinase (FAK)-mediated integrin signalling and PI3K⁄Akt signalling.Whereas TPD52-depleted cells showed the reverse effect. These data suggested that MAL2 and TPD52 might be potential biomarkers for clinical prognosis and might be a promising therapeutic target for CRC.

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Section: Discussionsupporting

confidence: 88%

The four-transmembrane protein MAL2 and tumor protein D52 (TPD52) are highly expressed in colorectal cancer and correlated with poor prognosis

et al. 2017

PLoS ONE

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“…To explore whether CD166 plays a role in metastasis, we used two previously established metastatic pancreatic cancer cell lines that were generated from liver metastases in nude mouse xenograft models [15]. These cell lines, metastatic Panc-1 and metastatic SUIT-2, showed a stronger liver metastatic potential compared with that of their parental cell lines.…”

Section: Resultsmentioning

confidence: 99%

“…We examined the relationship between CD166 expression and metastatic potential in two previously established metastatic pancreatic cancer cell lines [15]. In these cell lines, the levels of CD166 mRNA expression were greater than those in their parental cell lines.…”

Section: Discussionmentioning

confidence: 99%

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CD166/ALCAM Expression Is Characteristic of Tumorigenicity and Invasive and Migratory Activities of Pancreatic Cancer Cells

et al. 2014

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BackgroundCD166, also known as activated leukocyte cell adhesion molecule (ALCAM), is expressed by various cells in several tissues including cancer. However, the role of CD166 in malignant tumors is controversial, especially in pancreatic cancer. This study aimed to clarify the role and significance of CD166 expression in pancreatic cancer.MethodsWe performed immunohistochemistry and flow cytometry to analyze the expression of CD166 in surgical pancreatic tissues and pancreatic cancer cell lines. The differences between isolated CD166+ and CD166- pancreatic cancer cells were analyzed by invasion and migration assays, and in mouse xenograft models. We also performed quantitative RT-PCR and microarray analyses to evaluate the expression levels of CD166 and related genes in cultured cells.ResultsImmunohistochemistry revealed high expression of CD166 in pancreatic cancer tissues (12.2%; 12/98) compared with that in normal pancreas controls (0%; 0/17) (p = 0.0435). Flow cytometry indicated that CD166 was expressed in 33.8–70.2% of cells in surgical pancreatic tissues and 0–99.5% of pancreatic cancer cell lines. Invasion and migration assays demonstrated that CD166- pancreatic cancer cells showed stronger invasive and migratory activities than those of CD166+ cancer cells (p<0.05). On the other hand, CD166+ Panc-1 cells showed a significantly stronger colony formation activity than that of CD166- Panc-1 cells (p<0.05). In vivo analysis revealed that CD166+ cells elicited significantly greater tumor growth than that of CD166- cells (p<0.05) in both subcutaneous and orthotopic mouse tumor models. mRNA expression of the epithelial-mesenchymal transition activator Zeb1 was over-expressed in CD166- cells (p<0.001). Microarray analysis showed that TSPAN8 and BST2 were over-expressed in CD166+ cells, while BMP7 and Col6A1 were over-expressed in CD166- cells.ConclusionsCD166+ pancreatic cancer cells are strongly tumorigenic, while CD166- pancreatic cancer cells exhibit comparatively stronger invasive and migratory activities. These findings suggest that CD166 expression is related to different functions in pancreatic cancer cells.

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“…MAL2, Mal, T-cell differentiation protein 2, has been identified as a molecule predictive of metastases whose increased expression has been validated in ovarian, colorectal and pancreatic cancer41. CST642 is a breast tumor suppressor expressed in normal breast epithelium, but epigenetically silenced as a consequence of promoter hypermethylation in metastatic breast cancer cell lines, which suggests the mechanism of CST6 loss during breast tumorigenesis and/or progression to metastasis.…”

Section: Discussionmentioning

confidence: 99%

Exploring the intrinsic differences among breast tumor subtypes defined using immunohistochemistry markers based on the decision tree

Bai

Dai

2016

Sci Rep

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Exploring the intrinsic differences among breast cancer subtypes is of crucial importance for precise diagnosis and therapeutic decision-making in diseases of high heterogeneity. The subtypes defined with several layers of information are related but not consistent, especially using immunohistochemistry markers and gene expression profiling. Here, we explored the intrinsic differences among the subtypes defined by the estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 based on the decision tree. We identified 30 mRNAs and 7 miRNAs differentially expressed along the tree’s branches. The final signature panel contained 30 mRNAs, whose performance was validated using two public datasets based on 3 well-known classifiers. The network and pathway analysis were explored for feature genes, from which key molecules including FOXQ1 and SFRP1 were revealed to be densely connected with other molecules and participate in the validated metabolic pathways. Our study uncovered the differences among the four IHC-defined breast tumor subtypes at the mRNA and miRNA levels, presented a novel signature for breast tumor subtyping, and identified several key molecules potentially driving the heterogeneity of such tumors. The results help us further understand breast tumor heterogeneity, which could be availed in clinics.

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MAL2 expression predicts distant metastasis and short survival in pancreatic cancer

Cited by 34 publications

References 31 publications

The four-transmembrane protein MAL2 and tumor protein D52 (TPD52) are highly expressed in colorectal cancer and correlated with poor prognosis

The four-transmembrane protein MAL2 and tumor protein D52 (TPD52) are highly expressed in colorectal cancer and correlated with poor prognosis

CD166/ALCAM Expression Is Characteristic of Tumorigenicity and Invasive and Migratory Activities of Pancreatic Cancer Cells

Exploring the intrinsic differences among breast tumor subtypes defined using immunohistochemistry markers based on the decision tree

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