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Fibulin-1 is downregulated through promoter hypermethylation in colorectal cancer: a CONSORT study.

Xu Z, Chen H, Liu D, Huo J - Medicine (Baltimore) (2015)

Bottom Line: Furthermore, the methylated level of FBLN1 was analyzed with the clinicopathological characteristics.The methylation rate of FBLN1 promoter was significantly higher in CRC tissues than that in adjacent nontumor tissues (P < 0.001).In addition, the correlation between FBLN1 hypermethylation, protein expression, and overall survival (OS) was statistically significant.

View Article: PubMed Central - PubMed

Affiliation: From the Department of Gastroenterology (ZX, DL, JH), 2nd Xiangya Hospital, Central South University, Changsha, Hunan; and Department of Gastroenterology (ZX, HC), People's Hospital of Taizhou, Taizhou, Jiangsu, China.

ABSTRACT
Fibulin-1 (FBLN1) is involved in the progression of some types of cancer. However, the role of FBLN1 in colorectal cancer (CRC) has not been examined. The purpose of this study was to understand the molecular mechanisms and clinical significance of FBLN1 inactivation in CRC. The expression of FBLN1 in CRC tissues and adjacent normal tissues was analyzed by immunohistochemical analysis and quantitative real-time polymerase chain reaction (qRT-PCR). Methylation-specific polymerase chain reaction (MSP) and bisulfite sequencing PCR (BSP) were performed to examine the methylation status of the FBLN1 gene promoter. Furthermore, the methylated level of FBLN1 was analyzed with the clinicopathological characteristics. Immunohistochemical analysis and qRT-PCR analysis showed that FBLN1 protein and messenger RNA (mRNA) levels in tumor tissues were both significantly decreased compared with that in adjacent nontumor tissues. The methylation rate of FBLN1 promoter was significantly higher in CRC tissues than that in adjacent nontumor tissues (P < 0.001). In addition, the correlation between FBLN1 hypermethylation, protein expression, and overall survival (OS) was statistically significant. Our results indicated that the FBLN1 gene may be a novel candidate of tumor suppressor gene in CRC, and that promoter hypermethylation of FBLN1 is an important reason for its downregulation and is also a good predictor of OS for CRC.

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Determination of FBLN1 expression levels. (A) Immunohistochemical analysis of FBLN1. Paraffin-embedded tissue sections from CRC and adjacent normal tissues were used for immunohistochemical analysis of FBLN1 protein with monoclonal antibody of FBLN1. The photomicrograph shows a CRC sample (left) showing low-level expression of FBLN1, and an adjacent nontumor tissue (right) showing high-level expression. (B) The relative mRNA levels of FBLN1 were compared between CRC tissues and adjacent nontumor tissues. (CRC = colorectal cancer; FBLN1 = fibulin-1; mRNA = messenger RNA). ∗∗P < 0.001.
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Figure 2: Determination of FBLN1 expression levels. (A) Immunohistochemical analysis of FBLN1. Paraffin-embedded tissue sections from CRC and adjacent normal tissues were used for immunohistochemical analysis of FBLN1 protein with monoclonal antibody of FBLN1. The photomicrograph shows a CRC sample (left) showing low-level expression of FBLN1, and an adjacent nontumor tissue (right) showing high-level expression. (B) The relative mRNA levels of FBLN1 were compared between CRC tissues and adjacent nontumor tissues. (CRC = colorectal cancer; FBLN1 = fibulin-1; mRNA = messenger RNA). ∗∗P < 0.001.

Mentions: We measured the expression of FBLN1 by immunohistochemical analysis in 68 pairs of tumor and adjacent nontumor tissues. As shown in Figure 2A, the expression levels of FBLN1 protein were significantly downregulated in tumor tissues compared with nontumor tissues. Decreased expression of FBLN1 protein in 49 (72%) of 68 CRC tissues was shown (Table 2). We also determined the FBLN1 mRNA levels by qRT-PCR. The result showed that the FBLN1 mRNA levels were also decreased in CRC, compared with that of normal tissues (P < 0.001, Figure 2B). Comparison of methylation data with immunohistochemistry findings revealed low-level or loss of FBLN1 protein expression in 48 (81.4%) of the 59 tumors harboring FBLN1 hypermethylation. In contrast, increased expression of FBLN1 protein was observed in 8/9 (88.9%) of low-level methylated tumors and reduced expression was only observed in 1/9 (11.1%) (Table 2). There was a significant association between FBLN1 promoter hypermethylation and its protein expression (P < 0.001, Table 2).


Fibulin-1 is downregulated through promoter hypermethylation in colorectal cancer: a CONSORT study.

Xu Z, Chen H, Liu D, Huo J - Medicine (Baltimore) (2015)

Determination of FBLN1 expression levels. (A) Immunohistochemical analysis of FBLN1. Paraffin-embedded tissue sections from CRC and adjacent normal tissues were used for immunohistochemical analysis of FBLN1 protein with monoclonal antibody of FBLN1. The photomicrograph shows a CRC sample (left) showing low-level expression of FBLN1, and an adjacent nontumor tissue (right) showing high-level expression. (B) The relative mRNA levels of FBLN1 were compared between CRC tissues and adjacent nontumor tissues. (CRC = colorectal cancer; FBLN1 = fibulin-1; mRNA = messenger RNA). ∗∗P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554035&req=5

Figure 2: Determination of FBLN1 expression levels. (A) Immunohistochemical analysis of FBLN1. Paraffin-embedded tissue sections from CRC and adjacent normal tissues were used for immunohistochemical analysis of FBLN1 protein with monoclonal antibody of FBLN1. The photomicrograph shows a CRC sample (left) showing low-level expression of FBLN1, and an adjacent nontumor tissue (right) showing high-level expression. (B) The relative mRNA levels of FBLN1 were compared between CRC tissues and adjacent nontumor tissues. (CRC = colorectal cancer; FBLN1 = fibulin-1; mRNA = messenger RNA). ∗∗P < 0.001.
Mentions: We measured the expression of FBLN1 by immunohistochemical analysis in 68 pairs of tumor and adjacent nontumor tissues. As shown in Figure 2A, the expression levels of FBLN1 protein were significantly downregulated in tumor tissues compared with nontumor tissues. Decreased expression of FBLN1 protein in 49 (72%) of 68 CRC tissues was shown (Table 2). We also determined the FBLN1 mRNA levels by qRT-PCR. The result showed that the FBLN1 mRNA levels were also decreased in CRC, compared with that of normal tissues (P < 0.001, Figure 2B). Comparison of methylation data with immunohistochemistry findings revealed low-level or loss of FBLN1 protein expression in 48 (81.4%) of the 59 tumors harboring FBLN1 hypermethylation. In contrast, increased expression of FBLN1 protein was observed in 8/9 (88.9%) of low-level methylated tumors and reduced expression was only observed in 1/9 (11.1%) (Table 2). There was a significant association between FBLN1 promoter hypermethylation and its protein expression (P < 0.001, Table 2).

Bottom Line: Furthermore, the methylated level of FBLN1 was analyzed with the clinicopathological characteristics.The methylation rate of FBLN1 promoter was significantly higher in CRC tissues than that in adjacent nontumor tissues (P < 0.001).In addition, the correlation between FBLN1 hypermethylation, protein expression, and overall survival (OS) was statistically significant.

View Article: PubMed Central - PubMed

Affiliation: From the Department of Gastroenterology (ZX, DL, JH), 2nd Xiangya Hospital, Central South University, Changsha, Hunan; and Department of Gastroenterology (ZX, HC), People's Hospital of Taizhou, Taizhou, Jiangsu, China.

ABSTRACT
Fibulin-1 (FBLN1) is involved in the progression of some types of cancer. However, the role of FBLN1 in colorectal cancer (CRC) has not been examined. The purpose of this study was to understand the molecular mechanisms and clinical significance of FBLN1 inactivation in CRC. The expression of FBLN1 in CRC tissues and adjacent normal tissues was analyzed by immunohistochemical analysis and quantitative real-time polymerase chain reaction (qRT-PCR). Methylation-specific polymerase chain reaction (MSP) and bisulfite sequencing PCR (BSP) were performed to examine the methylation status of the FBLN1 gene promoter. Furthermore, the methylated level of FBLN1 was analyzed with the clinicopathological characteristics. Immunohistochemical analysis and qRT-PCR analysis showed that FBLN1 protein and messenger RNA (mRNA) levels in tumor tissues were both significantly decreased compared with that in adjacent nontumor tissues. The methylation rate of FBLN1 promoter was significantly higher in CRC tissues than that in adjacent nontumor tissues (P < 0.001). In addition, the correlation between FBLN1 hypermethylation, protein expression, and overall survival (OS) was statistically significant. Our results indicated that the FBLN1 gene may be a novel candidate of tumor suppressor gene in CRC, and that promoter hypermethylation of FBLN1 is an important reason for its downregulation and is also a good predictor of OS for CRC.

Show MeSH
Related in: MedlinePlus