Loss of carcinoembryonic antigen‐related cell adhesion molecule 1 expression is an adverse prognostic factor in hepatocellular carcinoma

Cruz, Pauldion V.; Wakai, Toshifumi; Shirai, Yoshio; Yokoyama, Naoyuki; Hatakeyama, Katsuyoshi

doi:10.1002/cncr.21159

Cited by 34 publications

(28 citation statements)

References 32 publications

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“…The CEACAM1 protein expression levels in primary OSCCs were significantly associated with tumor size (p = 0.022). In hepatocellular carcinomas, a clinical study also reported that decreased CEACAM1 expression was correlated with larger tumors [41], which was consistent with the results obtained in this study. Moreover, the status of the protein CEACAM1 expression differed significantly between the early stages (I and II) and the advanced stages (III and IV; Mann-Whitney U test; p < 0.001).…”

Section: Discussionsupporting

confidence: 83%

“…Decreased expression of CEACAM1 has been reported in many malignant tumors of the breast [33], colon [34], endometrium [35], prostate [36,37,38], bladder [39] and liver [40, 41]. Based on these results, we postulated that CEACAM1 may have a tumor-suppressive role.…”

Section: Discussionmentioning

confidence: 67%

“…Human prostate and colon cancer cells show diminished tumorigenesis when transfected with CEACAM1 [36, 37, 42]. Furthermore, loss of CEACAM1 is also an adverse prognostic factor in hepatocellular carcinoma [41]. Recently, CEACAM1 was reported to restrict tumor growth in thyroid cancer [43].…”

Section: Discussionmentioning

confidence: 99%

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Downregulation of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 in Oral Squamous Cell Carcinoma: Correlation with Tumor Progression and Poor Prognosis

et al. 2009

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Objective: To identify genes associated with therapeutic targets of oral squamous cell carcinoma (OSCC), we compared gene expression profiles in OSCC-derived cell lines with human normal oral keratinocytes. Methods: We analyzed the gene expression profiles of OSCCs using Affymetrix GeneChip analysis. The identified genes were analyzed by an Ingenuity Pathway Analysis tool to identify networks of interacting genes. A candidate gene was further evaluated for the expression status of the mRNA and protein in OSCC-derived cell lines and primary OSCCs. Results: The microarray data identified 188 genes downregulated in OSCC-derived cell lines, and the genetic pathways associated with expression changes were generated. Among the genes mapped to the network with the highest significance, carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) was analyzed further. CEACAM1 mRNA and protein were frequently downregulated in OSCC-derived cell lines compared with human normal oral keratinocytes. Immunohistochemical analysis showed that primary OSCCs were significantly decreased in CEACAM1. Moreover, CEACAM1 expression was correlated with the TNM staging. We also found that CEACAM1-negative expression was significant both for disease-free (p = 0.036) and overall survival (p = 0.032). Conclusion: Repression of CEACAM1 could contribute to cancer progression and may indicate a poor prognosis for patients with OSCC.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 67%

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Downregulation of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 in Oral Squamous Cell Carcinoma: Correlation with Tumor Progression and Poor Prognosis

et al. 2009

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“…Studies have shown that CEACAM1 expression in colon, hepatoma and prostate cancers can inhibit tumor growth. Loss of gene expression or downregulation has been frequently observed, indicating that it may act as a tumor suppressor [4-8]. CEACAM1 overexpression in thyroid and non-small cell cancer and melanomas are often associated with poor clinical outcome and poor survival [8-11].…”

Section: Introductionmentioning

confidence: 99%

Characterizing the Tumor Suppressor Role of CEACAM1 in Multiple Myeloma

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), also known as CD66a, is a member of the immunoglobulin (Ig) superfamily that belongs to the carcinoembryonic antigen (CEA) family which plays a dual role in cancer. Previous studies showed high expression of CEACAM1 in multiple myeloma (MM). The aim of this study was to investigate the biological consequences of CEACAM1 overexpression in MM. Methods: pEGFP-N1-CEACAM1 and pcDNA3.1-CEACAM1 expression plasmids were transfected into U-266 and RPMI8266 cell lines . Effect of CEACAM1 overexpression on the proliferation of two cell lines were tested by the CCK8 assay. Cell cycle and Apoptotic changes after CEACAM1 transfection were examined with AnnexinV–FITC/PI by flow cytometry. Hochest staining assay was used to confirm the apoptotic changes. Caspase-3 activity was examined by Western blotting. The cell invasion and migration activity change after CEACAM1 transfection were performed by well chamber assays and a wound healing, respectively. MMP-2 and MMP-9 proteins expression were detected by Western blotting. Flow cytometry immunophenotyping was be evaluated on myeloma cells from bone marrow taken from 50 patients with symptomatic MM newly diagnosed. The correlations between CEACAM1 expression levels and the clinical features across all groups were investigated. Results: CEACAM1 overexpression significantly suppressed MM cell proliferation, induced cell apoptosis, and inhibited cell invasion and migration possibly through activation of caspase-3 and downregulation of MMP-2 and MMP-9. CEACAM1 expression in patients with DS stage I was more frequent (61.5%) than those with DS stage II (21.1%) or III (22.2%). Furthermore, patients with β2-microglobulin levels equal to or less than 3.5 mg/L had higher CEACAM1 expression than those with β2-microglobulin levels greater than 3.5 mg/L. Conclusion: Our findings suggest that CEACAM1 may act as a tumor suppressor in MM.

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“…The decision to use neoadjuvant chemotherapy was made by the Institutional Cancer Committee of Niigata University Medical and Dental Hospital. Indications for neoadjuvant chemotherapy included multiple hepatic tumors or a solitary tumor >3 cm in diameter, because these preoperative factors are closely associated with vascular invasion or poor post-resection survival (15)(16)(17). In the current series, 16 patients received neoadjuvant chemotherapy, which consisted of hepatic arterial infusion of a fine-powder formulation of cisplatin (IA-call ® , Nippon Kayaku, Co., Ltd., Tokyo, Japan; recommended dose of 65 mg/m 2 ) under the guidance of hepatic angiography.…”

Section: Patient Population From March 2007 Through Decembermentioning

confidence: 99%

Multidrug resistance-associated protein 2 determines the efficacy of cisplatin in patients with hepatocellular carcinoma

Korita

Wakai²,

Shirai³

et al. 2010

Oncol Rep

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Abstract.We hypothesized that expression of multidrug resistance-associated protein 2 (MRP2), a major cisplatin transporter, may determine the efficacy of cisplatin as a treatment for patients with hepatocellular carcinoma (HCC). A prospective analysis was conducted of 49 consecutive patients who underwent resection for HCC (16 patients treated with cisplatin-based neoadjuvant chemotherapy and 33 patients treated without neoadjuvant chemotherapy). Expression of MRP2 in resected specimens was assessed by immunohistochemical and Western blot analyses. The extent of tumor necrosis was assessed histologically in the greatest dimension of the tumor specimen from each patient. The median percentage of tumor necrosis was 81% (range: 0-100%) and complete tumor necrosis was found in 3 patients. Overexpression of MRP2 was detected in 24/46 (52%) tumor specimens. In 16 patients treated with cisplatin, tumor size and dose of cisplatin did not correlate with tumor necrosis of the resected specimens (P=0.706 and P=0.555, respectively). Of 13 tumor specimens containing vivid tumor from 16 patients treated with cisplatin, 8 had overexpression of MRP2. Tumor specimens with overexpression of MRP2 showed a lower percentage of tumor necrosis than those with non-overexpression (median percentage of tumor necrosis, 19% vs. 99%, P=0.003). In conclusion, overexpression of MRP2 correlates with a lower percentage of tumor necrosis in patients treated with cisplatin-based neoadjuvant chemotherapy for HCC, whereas either tumor size or dose of cisplatin does not. Expression of MRP2 determines the efficacy of cisplatinbased chemotherapy in patients with HCC.

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Loss of carcinoembryonic antigen‐related cell adhesion molecule 1 expression is an adverse prognostic factor in hepatocellular carcinoma

Cited by 34 publications

References 32 publications

Downregulation of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 in Oral Squamous Cell Carcinoma: Correlation with Tumor Progression and Poor Prognosis

Downregulation of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 in Oral Squamous Cell Carcinoma: Correlation with Tumor Progression and Poor Prognosis

Characterizing the Tumor Suppressor Role of CEACAM1 in Multiple Myeloma

Multidrug resistance-associated protein 2 determines the efficacy of cisplatin in patients with hepatocellular carcinoma

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