The Experts below are selected from a list of 1778580 Experts worldwide ranked by ideXlab platform
Didier Merlin - One of the best experts on this subject based on the ideXlab platform.
-
Homeostatic and innate immune responses: role of the transmembrane glycoprotein CD98
Cellular and Molecular Life Sciences, 2012Co-Authors: Hang Thi Thu Nguyen, Didier MerlinAbstract:The transmembrane glycoprotein CD98 is a potential regulator of multiple functions, including integrin signaling and amino acid transport. Abnormal expression or function of CD98 and disruption of the interactions between CD98 and its binding partners result in defects in cell homeostasis and immune responses. Indeed, expression of CD98 has been correlated with diseases such as inflammation and tumor metastasis. Modulation of CD98 expression and/or function therefore represents a promising therapeutic strategy for the treatment and prevention of such pathologies. Herein, we review the role of CD98 with focus on its functional importance in homeostasis and immune responses, which could help to better understand the pathogenesis of CD98-associated diseases.
-
Intestinal epithelial cell-specific CD98 expression regulates tumorigenesis in Apc Min/+ mice
Laboratory investigation; a journal of technical methods and pathology, 2012Co-Authors: Hang Thi Thu Nguyen, Hamed Laroui, Guillaume Dalmasso, Yutao Yan, Moiz Charania, Saravanan Ayyadurai, Yuchen Zhang, Shanthi V. Sitaraman, Sarah A. Ingersoll, Didier MerlinAbstract:The transmembrane glycoprotein CD98 regulates integrin signaling that in turn controls cell proliferation and survival. CD98 expression is upregulated in various carcinomas, including colorectal cancer. Recently, by generating gain- and loss-of-function mouse models featuring genetic manipulation of CD98 expression specifically in intestinal epithelial cells (IECs), we have explored the crucial role of CD98 in the regulation of intestinal homeostasis and inflammation-associated tumorigenesis. In the present study, we investigated the contribution of CD98 to intestinal tumorigenesis in ApcMin/+ mice and the underlying mechanism of action. Mice featuring IEC-specific CD98 overexpression (Tg animals) were crossed with ApcMin/+ mice, and the characteristics of intestinal adenoma formation were assessed. Compared with ApcMin/+ mice, Tg/ApcMin/+ animals exhibited increases in both intestinal tumor incidence and tumor size; these parameters correlated with enhanced proliferation and decreased apoptosis of IECs. IEC-specific CD98 overexpression resulted in increased synthesis of the oncogenic proteins c-myc and cyclin-D1 in ApcMin/+ mice, independently of the Wnt-APC-β-catenin pathway, suggesting the implication of CD98 overexpression-mediated Erk activation. IEC-specific CD98 overexpression enhanced the production of proinflammatory cytokines and chemokines that are crucial for tumorigenesis. We validated our results in mice exhibiting IEC-specific CD98 downregulation (CD98flox/+VillinCre animals). IEC-specific CD98 downregulation efficiently attenuated tumor incidence and growth in ApcMin/+ mice. The reduction of intestinal tumorigenesis upon IEC-specific CD98 downregulation was caused by the attenuation of IEC proliferation and cytokine/chemokine production. In conclusion, we show that CD98 exerts an oncogenic activity in terms of intestinal tumorigenesis, via an ability to regulate tumor growth and survival.
-
Intestinal epithelial cell-specific CD98 expression regulates tumorigenesis in Apc(Min/+) mice
Laboratory Investigation, 2012Co-Authors: - Hang Thi Thu Nguyen, Hamed Laroui, Guillaume Dalmasso, Yutao Yan, Moiz Charania, Sarah Ingersoll, Saravanan Ayyadurai, Yuchen Zhang, Shanthi Sitaraman, Didier MerlinAbstract:The transmembrane glycoprotein CD98 regulates integrin signaling that in turn controls cell proliferation and survival. CD98 expression is upregulated in various carcinomas, including colorectal cancer. Recently, by generating gain- and loss-of-function mouse models featuring genetic manipulation of CD98 expression specifically in intestinal epithelial cells (IECs), we have explored the crucial role of CD98 in the regulation of intestinal homeostasis and inflammation-associated tumorigenesis. In the present study, we investigated the contribution of CD98 to intestinal tumorigenesis in Apc(Min/+) mice and the underlying mechanism of action. Mice featuring IEC-specific CD98 overexpression (Tg animals) were crossed with Apc(Min/+) mice, and the characteristics of intestinal adenoma formation were assessed. Compared with Apc(Min/+) mice, Tg/Apc(Min/+) animals exhibited increases in both intestinal tumor incidence and tumor size; these parameters correlated with enhanced proliferation and decreased apoptosis of IECs. IEC-specific CD98 overexpression resulted in increased synthesis of the oncogenic proteins c-myc and cyclin-D1 in Apc(Min/+) mice, independently of the Wnt-APC-beta-catenin pathway, suggesting the implication of CD98 overexpression-mediated Erk activation. IEC-specific CD98 overexpression enhanced the production of proinflammatory cytokines and chemokines that are crucial for tumorigenesis. We validated our results in mice exhibiting IEC-specific CD98 downregulation (CD98(flox/+) VillinCre animals). IEC-specific CD98 downregulation efficiently attenuated tumor incidence and growth in Apc(Min/+) mice. The reduction of intestinal tumorigenesis upon IEC-specific CD98 downregulation was caused by the attenuation of IEC proliferation and cytokine/chemokine production. In conclusion, we show that CD98 exerts an oncogenic activity in terms of intestinal tumorigenesis, via an ability to regulate tumor growth and survival. Laboratory Investigation (2012) 92, 1203-1212; doi:10.1038/labinvest.2012.83; published online 21 May 2012
-
MicroRNA-7 Modulates CD98 Expression during Intestinal Epithelial Cell Differentiation
The Journal of biological chemistry, 2009Co-Authors: Hang Thi Thu Nguyen, Hamed Laroui, Guillaume Dalmasso, Yutao Yan, Stephanie Dahan, Lloyd Mayer, Shanthi V. Sitaraman, Didier MerlinAbstract:The transmembrane glycoprotein CD98 regulates multiple cellular functions, including extracellular signaling, epithelial cell adhesion/polarity, amino acid transport, and cell-cell interactions. MicroRNAs post-transcriptionally regulate gene expression, thereby functioning as modulators of numerous cellular processes, such as cell differentiation, proliferation, and apoptosis. Here, we investigated if microRNAs regulate CD98 expression during intestinal epithelial cell differentiation and inflammation. We found that microRNA-7 repressed CD98 expression in Caco2-BBE cells by directly targeting the 3′-untranslated region of human CD98 mRNA. Expression of CD98 was decreased, whereas that of microRNA-7 was increased in well-differentiated Caco2-BBE cells compared with undifferentiated cells. Undifferentiated crypt cells isolated from mouse jejunum showed higher CD98 levels and lower levels of mmu-microRNA-706, a murine original microRNA candidate for CD98, than well-differentiated villus cells. Importantly, microRNA-7 decreased Caco2-BBE cell attachment on laminin-1, and CD98 overexpression recovered this inhibition, suggesting that microRNA-7 modulates epithelial cell adhesion to extracellular matrix, which in turn could affect proliferation and differentiation during the migration of enterocytes across the crypt-villus axis, by regulating CD98 expression. In a pathological context, the pro-inflammatory cytokine interleukin 1-β increased CD98 expression in Caco2-BBE cells by decreasing microRNA-7 levels. Consistent with the in vitro findings, microRNA-7 levels were decreased in actively inflamed Crohn disease colonic tissues, where CD98 expression was up-regulated, compared with normal tissues. Together, these results reveal a novel mechanism underlying regulation of CD98 expression during patho-physiological states. This study raises microRNAs as a promising target for therapeutic modulations of CD98 expression in intestinal inflammatory disorders.
-
Ecto-Phosphorylation of CD98 Regulates Cell-Cell Interactions
PLOS ONE, 2008Co-Authors: Hang Thi Thu Nguyen, Guillaume Dalmasso, Shanthi V. Sitaraman, Tracy S. Obertone, Didier MerlinAbstract:Ecto-phosphorylation plays an important role in many cellular functions. The transmembrane glycoprotein CD98 contains potential phosphorylation sites in its extracellular C-terminal tail. We hypothesized that extracellular signaling through ecto-protein kinases (ePKs) might lead to ecto-phosphorylation of CD98 and influence its multiple functions, including its role in cell-cell interactions. Our results show that recombinant CD98 was phosphorylated in vitro by ePKs from Jurkat cells and by the commercial casein kinase 2 (CK2). Alanine substitutions at serines-305/307/309 or serines-426/430 attenuated CK2-mediated CD98 phosphorylation, suggesting that these residues are the dominant phosphorylation sites for CK2. Furthermore, CD98 expressed in the basolateral membranes of intestinal epithelial Caco2-BBE cells was ecto-phosphorylated by Jurkat cell-derived ePKs and ecto-CK2 was involved in this process. Importantly, cell attachment studies showed that the ecto-phosphorylation of CD98 enhanced heterotypic cell-cell interactions and that the extracellular domain of CD98, which possesses the serine phosphorylation sites, was crucial for this effect. In addition, phosphorylation of recombinant CD98 increased its interactions with Jurkat and Caco2-BBE cells, and promoted cell attachment and spreading. In conclusion, here we demonstrated the ecto-phosphorylation of CD98 by ePKs and its functional importance in cell-cell interactions. Our findings reveal a novel mechanism involved in regulating the multiple functions of CD98 and raise CD98 as a promising target for therapeutic modulations of cell-cell interactions.
Tetsunari Oyama - One of the best experts on this subject based on the ideXlab platform.
-
Prognostic Significance of the Expression of CD98 (4F2hc) in Gastric Cancer.
Anticancer research, 2017Co-Authors: Taisuke Satoh, Jun Horiguchi, Yoshikatsu Kanai, Kyoichi Kaira, Kengo Takahashi, Norihumi Takahashi, Takayuki Asao, Tetsunari OyamaAbstract:BACKGROUND CD98 expression is high in various human neoplasms. However, the relationship of CD98 expression with the clinicopathological factors of gastric cancer (GC) remains unclear. This study examined CD98 expression and its clinicopathological impact on GC. PATIENTS AND METHODS Three hundred and thirty-one patients with surgically resected GC were evaluated. Tumor sections were stained and analyzed using immunohistochemistry to assess CD98 expression. RESULTS CD98 was positively expressed in 19% (66/331) of our patient cohort. Increased CD98 expression was significantly associated with advanced GC stage, lymph node metastasis, non-signet histology, lymphatic permeation, and vascular invasion. Positive CD98 expression was also a significant prediction marker for unfavorable prognosis postoperatively. However, CD98 was not identified as GC's independent prognostic predictor. CONCLUSION CD98 could be a novel prediction marker for worse prognosis in GC-affected patients. Our data suggests that increased CD98 expression plays an essential role in tumor aggressiveness and metastasis.
-
correlation of l type amino acid transporter 1 and CD98 expression with triple negative breast cancer prognosis
Cancer Science, 2012Co-Authors: Mio Furuya, Jun Horiguchi, Hiroki Nakajima, Yoshikatsu Kanai, Tetsunari OyamaAbstract:Triple negative breast cancer (TNBC) is a heterogeneous, aggressive cancer for which there is no effective chemotherapy or targeted therapy. We aimed to evaluate L-type amino acid transporter (LAT) 1 and CD98 expression immunohistochemically in patients with breast cancer, especially TNBC. Out of 129 patients, LAT1 was positive in 56 patients (43.4%), and CD98 was positive in 41 patients (31.8%). The positive ratio of LAT1 expression in luminal A cases was 7.9%, 30.0% in luminal B cases, 71.4% in HER2 cases and 64.0% in TN cases. HER2 and TN subtypes expressed LAT1 and CD98 at higher levels than luminal A and B subtypes (both P < 0.001). LAT1 and CD98 expression correlated with tumor size (LAT1, P = 0.010; CD98, P = 0.007), nuclear grade (LAT1, P < 0.001; CD98, P < 0.001) and Ki67 labeling index (LAT1, P < 0.001; CD98, P = 0.001). LAT1 and CD98 expression was negatively associated with ER and PgR (both P < 0.001). In TNBC, the 5-year disease-free rate of CD98+ (63.6%) or LAT1+/CD98+ (61.9%) patients was significantly worse than that of CD98− (89.3%) patients or those with no co-expression of LAT1 and CD98 (89.7%), respectively (P = 0.014, P = 0.009). The 5-year survival rates of CD98 positive/negative patients were 77.3% and 100% (P = 0.050), respectively, whereas that of patients with LAT1+/CD98+ (76.2%) was significantly worse (100%) (P = 0.040). Multivariate analysis confirmed that CD98+ or LAT1+/CD98+ expression were risk factors for relapse in TNBC (P = 0.023, P = 0.019). Thus, in the present study we show that LAT1 and CD98 expression are prognostic factors. Inhibition of these proteins might provide a new therapeutic strategy in TNBC. (Cancer Sci 2012; 103: 382–389)
-
correlation of l type amino acid transporter 1 and CD98 expression with triple negative breast cancer prognosis
Cancer Science, 2012Co-Authors: Mio Furuya, Jun Horiguchi, Hiroki Nakajima, Yoshikatsu Kanai, Tetsunari OyamaAbstract:Triple negative breast cancer (TNBC) is a heterogeneous, aggressive cancer for which there is no effective chemotherapy or targeted therapy. We aimed to evaluate L-type amino acid transporter (LAT) 1 and CD98 expression immunohistochemically in patients with breast cancer, especially TNBC. Out of 129 patients, LAT1 was positive in 56 patients (43.4%), and CD98 was positive in 41 patients (31.8%). The positive ratio of LAT1 expression in luminal A cases was 7.9%, 30.0% in luminal B cases, 71.4% in HER2 cases and 64.0% in TN cases. HER2 and TN subtypes expressed LAT1 and CD98 at higher levels than luminal A and B subtypes (both P < 0.001). LAT1 and CD98 expression correlated with tumor size (LAT1, P = 0.010; CD98, P = 0.007), nuclear grade (LAT1, P < 0.001; CD98, P < 0.001) and Ki67 labeling index (LAT1, P < 0.001; CD98, P = 0.001). LAT1 and CD98 expression was negatively associated with ER and PgR (both P < 0.001). In TNBC, the 5-year disease-free rate of CD98+ (63.6%) or LAT1+/CD98+ (61.9%) patients was significantly worse than that of CD98- (89.3%) patients or those with no co-expression of LAT1 and CD98 (89.7%), respectively (P = 0.014, P = 0.009). The 5-year survival rates of CD98 positive/negative patients were 77.3% and 100% (P = 0.050), respectively, whereas that of patients with LAT1+/CD98+ (76.2%) was significantly worse (100%) (P = 0.040). Multivariate analysis confirmed that CD98+ or LAT1+/CD98+ expression were risk factors for relapse in TNBC (P = 0.023, P = 0.019). Thus, in the present study we show that LAT1 and CD98 expression are prognostic factors. Inhibition of these proteins might provide a new therapeutic strategy in TNBC.
Mio Furuya - One of the best experts on this subject based on the ideXlab platform.
-
correlation of l type amino acid transporter 1 and CD98 expression with triple negative breast cancer prognosis
Cancer Science, 2012Co-Authors: Mio Furuya, Jun Horiguchi, Hiroki Nakajima, Yoshikatsu Kanai, Tetsunari OyamaAbstract:Triple negative breast cancer (TNBC) is a heterogeneous, aggressive cancer for which there is no effective chemotherapy or targeted therapy. We aimed to evaluate L-type amino acid transporter (LAT) 1 and CD98 expression immunohistochemically in patients with breast cancer, especially TNBC. Out of 129 patients, LAT1 was positive in 56 patients (43.4%), and CD98 was positive in 41 patients (31.8%). The positive ratio of LAT1 expression in luminal A cases was 7.9%, 30.0% in luminal B cases, 71.4% in HER2 cases and 64.0% in TN cases. HER2 and TN subtypes expressed LAT1 and CD98 at higher levels than luminal A and B subtypes (both P < 0.001). LAT1 and CD98 expression correlated with tumor size (LAT1, P = 0.010; CD98, P = 0.007), nuclear grade (LAT1, P < 0.001; CD98, P < 0.001) and Ki67 labeling index (LAT1, P < 0.001; CD98, P = 0.001). LAT1 and CD98 expression was negatively associated with ER and PgR (both P < 0.001). In TNBC, the 5-year disease-free rate of CD98+ (63.6%) or LAT1+/CD98+ (61.9%) patients was significantly worse than that of CD98− (89.3%) patients or those with no co-expression of LAT1 and CD98 (89.7%), respectively (P = 0.014, P = 0.009). The 5-year survival rates of CD98 positive/negative patients were 77.3% and 100% (P = 0.050), respectively, whereas that of patients with LAT1+/CD98+ (76.2%) was significantly worse (100%) (P = 0.040). Multivariate analysis confirmed that CD98+ or LAT1+/CD98+ expression were risk factors for relapse in TNBC (P = 0.023, P = 0.019). Thus, in the present study we show that LAT1 and CD98 expression are prognostic factors. Inhibition of these proteins might provide a new therapeutic strategy in TNBC. (Cancer Sci 2012; 103: 382–389)
-
correlation of l type amino acid transporter 1 and CD98 expression with triple negative breast cancer prognosis
Cancer Science, 2012Co-Authors: Mio Furuya, Jun Horiguchi, Hiroki Nakajima, Yoshikatsu Kanai, Tetsunari OyamaAbstract:Triple negative breast cancer (TNBC) is a heterogeneous, aggressive cancer for which there is no effective chemotherapy or targeted therapy. We aimed to evaluate L-type amino acid transporter (LAT) 1 and CD98 expression immunohistochemically in patients with breast cancer, especially TNBC. Out of 129 patients, LAT1 was positive in 56 patients (43.4%), and CD98 was positive in 41 patients (31.8%). The positive ratio of LAT1 expression in luminal A cases was 7.9%, 30.0% in luminal B cases, 71.4% in HER2 cases and 64.0% in TN cases. HER2 and TN subtypes expressed LAT1 and CD98 at higher levels than luminal A and B subtypes (both P < 0.001). LAT1 and CD98 expression correlated with tumor size (LAT1, P = 0.010; CD98, P = 0.007), nuclear grade (LAT1, P < 0.001; CD98, P < 0.001) and Ki67 labeling index (LAT1, P < 0.001; CD98, P = 0.001). LAT1 and CD98 expression was negatively associated with ER and PgR (both P < 0.001). In TNBC, the 5-year disease-free rate of CD98+ (63.6%) or LAT1+/CD98+ (61.9%) patients was significantly worse than that of CD98- (89.3%) patients or those with no co-expression of LAT1 and CD98 (89.7%), respectively (P = 0.014, P = 0.009). The 5-year survival rates of CD98 positive/negative patients were 77.3% and 100% (P = 0.050), respectively, whereas that of patients with LAT1+/CD98+ (76.2%) was significantly worse (100%) (P = 0.040). Multivariate analysis confirmed that CD98+ or LAT1+/CD98+ expression were risk factors for relapse in TNBC (P = 0.023, P = 0.019). Thus, in the present study we show that LAT1 and CD98 expression are prognostic factors. Inhibition of these proteins might provide a new therapeutic strategy in TNBC.
Yoshikatsu Kanai - One of the best experts on this subject based on the ideXlab platform.
-
Prognostic Significance of the Expression of CD98 (4F2hc) in Gastric Cancer.
Anticancer research, 2017Co-Authors: Taisuke Satoh, Jun Horiguchi, Yoshikatsu Kanai, Kyoichi Kaira, Kengo Takahashi, Norihumi Takahashi, Takayuki Asao, Tetsunari OyamaAbstract:BACKGROUND CD98 expression is high in various human neoplasms. However, the relationship of CD98 expression with the clinicopathological factors of gastric cancer (GC) remains unclear. This study examined CD98 expression and its clinicopathological impact on GC. PATIENTS AND METHODS Three hundred and thirty-one patients with surgically resected GC were evaluated. Tumor sections were stained and analyzed using immunohistochemistry to assess CD98 expression. RESULTS CD98 was positively expressed in 19% (66/331) of our patient cohort. Increased CD98 expression was significantly associated with advanced GC stage, lymph node metastasis, non-signet histology, lymphatic permeation, and vascular invasion. Positive CD98 expression was also a significant prediction marker for unfavorable prognosis postoperatively. However, CD98 was not identified as GC's independent prognostic predictor. CONCLUSION CD98 could be a novel prediction marker for worse prognosis in GC-affected patients. Our data suggests that increased CD98 expression plays an essential role in tumor aggressiveness and metastasis.
-
correlation of l type amino acid transporter 1 and CD98 expression with triple negative breast cancer prognosis
Cancer Science, 2012Co-Authors: Mio Furuya, Jun Horiguchi, Hiroki Nakajima, Yoshikatsu Kanai, Tetsunari OyamaAbstract:Triple negative breast cancer (TNBC) is a heterogeneous, aggressive cancer for which there is no effective chemotherapy or targeted therapy. We aimed to evaluate L-type amino acid transporter (LAT) 1 and CD98 expression immunohistochemically in patients with breast cancer, especially TNBC. Out of 129 patients, LAT1 was positive in 56 patients (43.4%), and CD98 was positive in 41 patients (31.8%). The positive ratio of LAT1 expression in luminal A cases was 7.9%, 30.0% in luminal B cases, 71.4% in HER2 cases and 64.0% in TN cases. HER2 and TN subtypes expressed LAT1 and CD98 at higher levels than luminal A and B subtypes (both P < 0.001). LAT1 and CD98 expression correlated with tumor size (LAT1, P = 0.010; CD98, P = 0.007), nuclear grade (LAT1, P < 0.001; CD98, P < 0.001) and Ki67 labeling index (LAT1, P < 0.001; CD98, P = 0.001). LAT1 and CD98 expression was negatively associated with ER and PgR (both P < 0.001). In TNBC, the 5-year disease-free rate of CD98+ (63.6%) or LAT1+/CD98+ (61.9%) patients was significantly worse than that of CD98− (89.3%) patients or those with no co-expression of LAT1 and CD98 (89.7%), respectively (P = 0.014, P = 0.009). The 5-year survival rates of CD98 positive/negative patients were 77.3% and 100% (P = 0.050), respectively, whereas that of patients with LAT1+/CD98+ (76.2%) was significantly worse (100%) (P = 0.040). Multivariate analysis confirmed that CD98+ or LAT1+/CD98+ expression were risk factors for relapse in TNBC (P = 0.023, P = 0.019). Thus, in the present study we show that LAT1 and CD98 expression are prognostic factors. Inhibition of these proteins might provide a new therapeutic strategy in TNBC. (Cancer Sci 2012; 103: 382–389)
-
correlation of l type amino acid transporter 1 and CD98 expression with triple negative breast cancer prognosis
Cancer Science, 2012Co-Authors: Mio Furuya, Jun Horiguchi, Hiroki Nakajima, Yoshikatsu Kanai, Tetsunari OyamaAbstract:Triple negative breast cancer (TNBC) is a heterogeneous, aggressive cancer for which there is no effective chemotherapy or targeted therapy. We aimed to evaluate L-type amino acid transporter (LAT) 1 and CD98 expression immunohistochemically in patients with breast cancer, especially TNBC. Out of 129 patients, LAT1 was positive in 56 patients (43.4%), and CD98 was positive in 41 patients (31.8%). The positive ratio of LAT1 expression in luminal A cases was 7.9%, 30.0% in luminal B cases, 71.4% in HER2 cases and 64.0% in TN cases. HER2 and TN subtypes expressed LAT1 and CD98 at higher levels than luminal A and B subtypes (both P < 0.001). LAT1 and CD98 expression correlated with tumor size (LAT1, P = 0.010; CD98, P = 0.007), nuclear grade (LAT1, P < 0.001; CD98, P < 0.001) and Ki67 labeling index (LAT1, P < 0.001; CD98, P = 0.001). LAT1 and CD98 expression was negatively associated with ER and PgR (both P < 0.001). In TNBC, the 5-year disease-free rate of CD98+ (63.6%) or LAT1+/CD98+ (61.9%) patients was significantly worse than that of CD98- (89.3%) patients or those with no co-expression of LAT1 and CD98 (89.7%), respectively (P = 0.014, P = 0.009). The 5-year survival rates of CD98 positive/negative patients were 77.3% and 100% (P = 0.050), respectively, whereas that of patients with LAT1+/CD98+ (76.2%) was significantly worse (100%) (P = 0.040). Multivariate analysis confirmed that CD98+ or LAT1+/CD98+ expression were risk factors for relapse in TNBC (P = 0.023, P = 0.019). Thus, in the present study we show that LAT1 and CD98 expression are prognostic factors. Inhibition of these proteins might provide a new therapeutic strategy in TNBC.
Jun Horiguchi - One of the best experts on this subject based on the ideXlab platform.
-
Prognostic Significance of the Expression of CD98 (4F2hc) in Gastric Cancer.
Anticancer research, 2017Co-Authors: Taisuke Satoh, Jun Horiguchi, Yoshikatsu Kanai, Kyoichi Kaira, Kengo Takahashi, Norihumi Takahashi, Takayuki Asao, Tetsunari OyamaAbstract:BACKGROUND CD98 expression is high in various human neoplasms. However, the relationship of CD98 expression with the clinicopathological factors of gastric cancer (GC) remains unclear. This study examined CD98 expression and its clinicopathological impact on GC. PATIENTS AND METHODS Three hundred and thirty-one patients with surgically resected GC were evaluated. Tumor sections were stained and analyzed using immunohistochemistry to assess CD98 expression. RESULTS CD98 was positively expressed in 19% (66/331) of our patient cohort. Increased CD98 expression was significantly associated with advanced GC stage, lymph node metastasis, non-signet histology, lymphatic permeation, and vascular invasion. Positive CD98 expression was also a significant prediction marker for unfavorable prognosis postoperatively. However, CD98 was not identified as GC's independent prognostic predictor. CONCLUSION CD98 could be a novel prediction marker for worse prognosis in GC-affected patients. Our data suggests that increased CD98 expression plays an essential role in tumor aggressiveness and metastasis.
-
correlation of l type amino acid transporter 1 and CD98 expression with triple negative breast cancer prognosis
Cancer Science, 2012Co-Authors: Mio Furuya, Jun Horiguchi, Hiroki Nakajima, Yoshikatsu Kanai, Tetsunari OyamaAbstract:Triple negative breast cancer (TNBC) is a heterogeneous, aggressive cancer for which there is no effective chemotherapy or targeted therapy. We aimed to evaluate L-type amino acid transporter (LAT) 1 and CD98 expression immunohistochemically in patients with breast cancer, especially TNBC. Out of 129 patients, LAT1 was positive in 56 patients (43.4%), and CD98 was positive in 41 patients (31.8%). The positive ratio of LAT1 expression in luminal A cases was 7.9%, 30.0% in luminal B cases, 71.4% in HER2 cases and 64.0% in TN cases. HER2 and TN subtypes expressed LAT1 and CD98 at higher levels than luminal A and B subtypes (both P < 0.001). LAT1 and CD98 expression correlated with tumor size (LAT1, P = 0.010; CD98, P = 0.007), nuclear grade (LAT1, P < 0.001; CD98, P < 0.001) and Ki67 labeling index (LAT1, P < 0.001; CD98, P = 0.001). LAT1 and CD98 expression was negatively associated with ER and PgR (both P < 0.001). In TNBC, the 5-year disease-free rate of CD98+ (63.6%) or LAT1+/CD98+ (61.9%) patients was significantly worse than that of CD98− (89.3%) patients or those with no co-expression of LAT1 and CD98 (89.7%), respectively (P = 0.014, P = 0.009). The 5-year survival rates of CD98 positive/negative patients were 77.3% and 100% (P = 0.050), respectively, whereas that of patients with LAT1+/CD98+ (76.2%) was significantly worse (100%) (P = 0.040). Multivariate analysis confirmed that CD98+ or LAT1+/CD98+ expression were risk factors for relapse in TNBC (P = 0.023, P = 0.019). Thus, in the present study we show that LAT1 and CD98 expression are prognostic factors. Inhibition of these proteins might provide a new therapeutic strategy in TNBC. (Cancer Sci 2012; 103: 382–389)
-
correlation of l type amino acid transporter 1 and CD98 expression with triple negative breast cancer prognosis
Cancer Science, 2012Co-Authors: Mio Furuya, Jun Horiguchi, Hiroki Nakajima, Yoshikatsu Kanai, Tetsunari OyamaAbstract:Triple negative breast cancer (TNBC) is a heterogeneous, aggressive cancer for which there is no effective chemotherapy or targeted therapy. We aimed to evaluate L-type amino acid transporter (LAT) 1 and CD98 expression immunohistochemically in patients with breast cancer, especially TNBC. Out of 129 patients, LAT1 was positive in 56 patients (43.4%), and CD98 was positive in 41 patients (31.8%). The positive ratio of LAT1 expression in luminal A cases was 7.9%, 30.0% in luminal B cases, 71.4% in HER2 cases and 64.0% in TN cases. HER2 and TN subtypes expressed LAT1 and CD98 at higher levels than luminal A and B subtypes (both P < 0.001). LAT1 and CD98 expression correlated with tumor size (LAT1, P = 0.010; CD98, P = 0.007), nuclear grade (LAT1, P < 0.001; CD98, P < 0.001) and Ki67 labeling index (LAT1, P < 0.001; CD98, P = 0.001). LAT1 and CD98 expression was negatively associated with ER and PgR (both P < 0.001). In TNBC, the 5-year disease-free rate of CD98+ (63.6%) or LAT1+/CD98+ (61.9%) patients was significantly worse than that of CD98- (89.3%) patients or those with no co-expression of LAT1 and CD98 (89.7%), respectively (P = 0.014, P = 0.009). The 5-year survival rates of CD98 positive/negative patients were 77.3% and 100% (P = 0.050), respectively, whereas that of patients with LAT1+/CD98+ (76.2%) was significantly worse (100%) (P = 0.040). Multivariate analysis confirmed that CD98+ or LAT1+/CD98+ expression were risk factors for relapse in TNBC (P = 0.023, P = 0.019). Thus, in the present study we show that LAT1 and CD98 expression are prognostic factors. Inhibition of these proteins might provide a new therapeutic strategy in TNBC.