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Expression of AKR1C3 and CNN3 as markers for detection of lymph node metastases in colorectal cancer.

Nakarai C, Osawa K, Akiyama M, Matsubara N, Ikeuchi H, Yamano T, Hirota S, Tomita N, Usami M, Kido Y - Clin. Exp. Med. (2014)

Bottom Line: The aim of the study was to identify a set of discriminating genes that could be used for the prediction of Lymph node (LN) metastasis in human colorectal cancer (CRC), and for this, we compared the whole genome profiles of two CRC cell lines (the primary cell line SW480 and its LN metastatic variant, SW620) and identified eight genes [S100 calcium-binding protein P; aldo-keto reductase family 1(AKR1), member B1 (aldose reductase; AKR1B1); AKR1, member C3 (AKR1C3); calponin 3, acidic; metastasis associated in colon cancer 1; hemoglobin, epsilon 1; trefoil factor 3; and FGGY carbohydrate kinase domain containing].These genes were examined by quantitative RT-PCR in tissues and LNs in 14 CRC patients and 11 control patients.There were significant correlations between the expression levels of AKR1C3 and CNN3.

View Article: PubMed Central - PubMed

Affiliation: Department of Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2, Tomogaoka, Suma-ku, Kobe, 654-0142, Japan.

ABSTRACT
The aim of the study was to identify a set of discriminating genes that could be used for the prediction of Lymph node (LN) metastasis in human colorectal cancer (CRC), and for this, we compared the whole genome profiles of two CRC cell lines (the primary cell line SW480 and its LN metastatic variant, SW620) and identified eight genes [S100 calcium-binding protein P; aldo-keto reductase family 1(AKR1), member B1 (aldose reductase; AKR1B1); AKR1, member C3 (AKR1C3); calponin 3, acidic; metastasis associated in colon cancer 1; hemoglobin, epsilon 1; trefoil factor 3; and FGGY carbohydrate kinase domain containing]. These genes were examined by quantitative RT-PCR in tissues and LNs in 14 CRC patients and 11 control patients. The level of AKR1C3 mRNA expression was significantly different between the Dukes' stage A, B, and C groups and the control group (p < 0.05, p < 0.001, and p < 0.001) and was also significantly different between Dukes' stage C and A or B groups (p < 0.05 and p < 0.001, respectively). The expression of CNN3 was significantly different between the Dukes' stage C and B or control groups (p < 0.001 and p < 0.01, respectively). There were significant correlations between the expression levels of AKR1C3 and CNN3. AKR1C3 and CNN3 expressions are more accurate and suitable markers for the diagnosis of LN metastasis than the other six genes examined in this study.

No MeSH data available.


Related in: MedlinePlus

Relative mRNA expression of S100P, AKR1C3, CNN3, AKR1B1, MACC1, HBE1, TFF3, and FGGY in lymph nodes (LNs) from colorectal cancer (CRC) patients categorized by Duke’s classification. Dots showed mRNA levels in 125 LNs from CRC patients with Dukes’ stage A, B, and C, compared with 35 LNs from ulcerative colitis patients as controls. Black dots indicate LNs with tumor cells, and gray dots indicate LNs without tumor cells identified by hematoxylin–eosin staining. Broken lines show cutoff values of eight genes in Table 4. Bars showed means. a The relative quantity values (Mean ± SD) of S100P are 53.17 ± 208.51, 1.30 ± 2.86, 1.10 ± 6.44, and 6.24 ± 16.00 (control, Dukes’ A, Dukes’ B, and Dukes’ C). b Those of AKR1C3 are 1.97 ± 3.14, 13.99 ± 17.82, 34.03 ± 201.50, and 87.72 ± 127.72. c Those of CNN3 are 5.46 ± 6.73, 5.73 ± 5.28, 4.06 ± 6.39, and 22.97 ± 26.78. d Those of AKR1B1 are 5.49 ± 7.29, 3.44 ± 2.72, 5.15 ± 15.99, and 3.64 ± 4.01. e Those of MACC1 are 4.53 ± 6.06, 10.87 ± 10.81, 6.43 ± 18.75, and 34.17 ± 95.53. f Those of HBE are 8.57 ± 22.92, 1.61 ± 4.06, 0.48 ± 1.14, and 5.52 ± 9.51. g Those of TFF3 are 7.75 ± 13.53, 13.54 ± 25.01, 5.48 ± 16.74, and 16.70 ± 43.65. h Those of FGGY are 6.45 ± 14.38, 3.67 ± 2.87, 3.20 ± 5.24, and 4.41 ± 4.33, respectively. The p values are based on Kruskal–Wallis test. +p<0.05, *p < 0.01 and **p < 0.001 are based on Mann–Whitney U test with a Bonferroni correction
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Fig2: Relative mRNA expression of S100P, AKR1C3, CNN3, AKR1B1, MACC1, HBE1, TFF3, and FGGY in lymph nodes (LNs) from colorectal cancer (CRC) patients categorized by Duke’s classification. Dots showed mRNA levels in 125 LNs from CRC patients with Dukes’ stage A, B, and C, compared with 35 LNs from ulcerative colitis patients as controls. Black dots indicate LNs with tumor cells, and gray dots indicate LNs without tumor cells identified by hematoxylin–eosin staining. Broken lines show cutoff values of eight genes in Table 4. Bars showed means. a The relative quantity values (Mean ± SD) of S100P are 53.17 ± 208.51, 1.30 ± 2.86, 1.10 ± 6.44, and 6.24 ± 16.00 (control, Dukes’ A, Dukes’ B, and Dukes’ C). b Those of AKR1C3 are 1.97 ± 3.14, 13.99 ± 17.82, 34.03 ± 201.50, and 87.72 ± 127.72. c Those of CNN3 are 5.46 ± 6.73, 5.73 ± 5.28, 4.06 ± 6.39, and 22.97 ± 26.78. d Those of AKR1B1 are 5.49 ± 7.29, 3.44 ± 2.72, 5.15 ± 15.99, and 3.64 ± 4.01. e Those of MACC1 are 4.53 ± 6.06, 10.87 ± 10.81, 6.43 ± 18.75, and 34.17 ± 95.53. f Those of HBE are 8.57 ± 22.92, 1.61 ± 4.06, 0.48 ± 1.14, and 5.52 ± 9.51. g Those of TFF3 are 7.75 ± 13.53, 13.54 ± 25.01, 5.48 ± 16.74, and 16.70 ± 43.65. h Those of FGGY are 6.45 ± 14.38, 3.67 ± 2.87, 3.20 ± 5.24, and 4.41 ± 4.33, respectively. The p values are based on Kruskal–Wallis test. +p<0.05, *p < 0.01 and **p < 0.001 are based on Mann–Whitney U test with a Bonferroni correction

Mentions: To investigate whether each gene was overexpressed in metastatic LNs from CRC, we measured mRNA expression in 12 LNs from patients categorized into Dukes’ stage A, 97 LNs from patients categorized into Dukes’ stage B, and 16 LNs from Dukes’ stage C. As a control, we also measured mRNA expression in 35 LNs dissected from UC patients. As shown in Fig. 2, each level of S100P, AKR1C3, CNN3,AKR1B1, MACC1, and HBE1 mRNA expression was significantly different among the Dukes’ stage A, B, and C groups and the control group (S100P, AKR1C3, CNN3: p < 0.001,; AKR1B1, MACC1,HBE1: p < 0.01, respectively; Kruskal–Wallis test). The level of AKR1C3 mRNA expression was significantly different between the Dukes’ stage A, B, and C groups and the control group (p < 0.05, p < 0.001, and p < 0.001, respectively; Mann–Whitney U test with a Bonferroni correction) and was also significantly different between Dukes’ stage C and Dukes’ stage A or Dukes’ stage B groups (p < 0.05 and p < 0.001, respectively). A subsequent Mann–Whitney U test with a Bonferroni correction showed that expression of CNN3 and MACC1 was significantly different between the Dukes’ stage B and C groups (p < 0.001, p < 0.01, respectively) and between the control and the Dukes’ stage C groups (p < 0.01, p < 0.05, respectively). The S100P and HBE1 were significantly different between the Dukes’ stage B and C groups (p < 0.001, p < 0.001, respectively), and the S100P and AKR1B1 were significantly different between the control and the Dukes’ stage B groups (p < 0.001, p < 0.05, respectively). On the other hand, there were no significant differences in TFF3 and FGGY mRNA expression among those four groups. The mRNA expression of AKR1C3, CNN3, and MACC1 was significantly higher in the Dukes’ stage C group than in the control group.Fig. 2


Expression of AKR1C3 and CNN3 as markers for detection of lymph node metastases in colorectal cancer.

Nakarai C, Osawa K, Akiyama M, Matsubara N, Ikeuchi H, Yamano T, Hirota S, Tomita N, Usami M, Kido Y - Clin. Exp. Med. (2014)

Relative mRNA expression of S100P, AKR1C3, CNN3, AKR1B1, MACC1, HBE1, TFF3, and FGGY in lymph nodes (LNs) from colorectal cancer (CRC) patients categorized by Duke’s classification. Dots showed mRNA levels in 125 LNs from CRC patients with Dukes’ stage A, B, and C, compared with 35 LNs from ulcerative colitis patients as controls. Black dots indicate LNs with tumor cells, and gray dots indicate LNs without tumor cells identified by hematoxylin–eosin staining. Broken lines show cutoff values of eight genes in Table 4. Bars showed means. a The relative quantity values (Mean ± SD) of S100P are 53.17 ± 208.51, 1.30 ± 2.86, 1.10 ± 6.44, and 6.24 ± 16.00 (control, Dukes’ A, Dukes’ B, and Dukes’ C). b Those of AKR1C3 are 1.97 ± 3.14, 13.99 ± 17.82, 34.03 ± 201.50, and 87.72 ± 127.72. c Those of CNN3 are 5.46 ± 6.73, 5.73 ± 5.28, 4.06 ± 6.39, and 22.97 ± 26.78. d Those of AKR1B1 are 5.49 ± 7.29, 3.44 ± 2.72, 5.15 ± 15.99, and 3.64 ± 4.01. e Those of MACC1 are 4.53 ± 6.06, 10.87 ± 10.81, 6.43 ± 18.75, and 34.17 ± 95.53. f Those of HBE are 8.57 ± 22.92, 1.61 ± 4.06, 0.48 ± 1.14, and 5.52 ± 9.51. g Those of TFF3 are 7.75 ± 13.53, 13.54 ± 25.01, 5.48 ± 16.74, and 16.70 ± 43.65. h Those of FGGY are 6.45 ± 14.38, 3.67 ± 2.87, 3.20 ± 5.24, and 4.41 ± 4.33, respectively. The p values are based on Kruskal–Wallis test. +p<0.05, *p < 0.01 and **p < 0.001 are based on Mann–Whitney U test with a Bonferroni correction
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Fig2: Relative mRNA expression of S100P, AKR1C3, CNN3, AKR1B1, MACC1, HBE1, TFF3, and FGGY in lymph nodes (LNs) from colorectal cancer (CRC) patients categorized by Duke’s classification. Dots showed mRNA levels in 125 LNs from CRC patients with Dukes’ stage A, B, and C, compared with 35 LNs from ulcerative colitis patients as controls. Black dots indicate LNs with tumor cells, and gray dots indicate LNs without tumor cells identified by hematoxylin–eosin staining. Broken lines show cutoff values of eight genes in Table 4. Bars showed means. a The relative quantity values (Mean ± SD) of S100P are 53.17 ± 208.51, 1.30 ± 2.86, 1.10 ± 6.44, and 6.24 ± 16.00 (control, Dukes’ A, Dukes’ B, and Dukes’ C). b Those of AKR1C3 are 1.97 ± 3.14, 13.99 ± 17.82, 34.03 ± 201.50, and 87.72 ± 127.72. c Those of CNN3 are 5.46 ± 6.73, 5.73 ± 5.28, 4.06 ± 6.39, and 22.97 ± 26.78. d Those of AKR1B1 are 5.49 ± 7.29, 3.44 ± 2.72, 5.15 ± 15.99, and 3.64 ± 4.01. e Those of MACC1 are 4.53 ± 6.06, 10.87 ± 10.81, 6.43 ± 18.75, and 34.17 ± 95.53. f Those of HBE are 8.57 ± 22.92, 1.61 ± 4.06, 0.48 ± 1.14, and 5.52 ± 9.51. g Those of TFF3 are 7.75 ± 13.53, 13.54 ± 25.01, 5.48 ± 16.74, and 16.70 ± 43.65. h Those of FGGY are 6.45 ± 14.38, 3.67 ± 2.87, 3.20 ± 5.24, and 4.41 ± 4.33, respectively. The p values are based on Kruskal–Wallis test. +p<0.05, *p < 0.01 and **p < 0.001 are based on Mann–Whitney U test with a Bonferroni correction
Mentions: To investigate whether each gene was overexpressed in metastatic LNs from CRC, we measured mRNA expression in 12 LNs from patients categorized into Dukes’ stage A, 97 LNs from patients categorized into Dukes’ stage B, and 16 LNs from Dukes’ stage C. As a control, we also measured mRNA expression in 35 LNs dissected from UC patients. As shown in Fig. 2, each level of S100P, AKR1C3, CNN3,AKR1B1, MACC1, and HBE1 mRNA expression was significantly different among the Dukes’ stage A, B, and C groups and the control group (S100P, AKR1C3, CNN3: p < 0.001,; AKR1B1, MACC1,HBE1: p < 0.01, respectively; Kruskal–Wallis test). The level of AKR1C3 mRNA expression was significantly different between the Dukes’ stage A, B, and C groups and the control group (p < 0.05, p < 0.001, and p < 0.001, respectively; Mann–Whitney U test with a Bonferroni correction) and was also significantly different between Dukes’ stage C and Dukes’ stage A or Dukes’ stage B groups (p < 0.05 and p < 0.001, respectively). A subsequent Mann–Whitney U test with a Bonferroni correction showed that expression of CNN3 and MACC1 was significantly different between the Dukes’ stage B and C groups (p < 0.001, p < 0.01, respectively) and between the control and the Dukes’ stage C groups (p < 0.01, p < 0.05, respectively). The S100P and HBE1 were significantly different between the Dukes’ stage B and C groups (p < 0.001, p < 0.001, respectively), and the S100P and AKR1B1 were significantly different between the control and the Dukes’ stage B groups (p < 0.001, p < 0.05, respectively). On the other hand, there were no significant differences in TFF3 and FGGY mRNA expression among those four groups. The mRNA expression of AKR1C3, CNN3, and MACC1 was significantly higher in the Dukes’ stage C group than in the control group.Fig. 2

Bottom Line: The aim of the study was to identify a set of discriminating genes that could be used for the prediction of Lymph node (LN) metastasis in human colorectal cancer (CRC), and for this, we compared the whole genome profiles of two CRC cell lines (the primary cell line SW480 and its LN metastatic variant, SW620) and identified eight genes [S100 calcium-binding protein P; aldo-keto reductase family 1(AKR1), member B1 (aldose reductase; AKR1B1); AKR1, member C3 (AKR1C3); calponin 3, acidic; metastasis associated in colon cancer 1; hemoglobin, epsilon 1; trefoil factor 3; and FGGY carbohydrate kinase domain containing].These genes were examined by quantitative RT-PCR in tissues and LNs in 14 CRC patients and 11 control patients.There were significant correlations between the expression levels of AKR1C3 and CNN3.

View Article: PubMed Central - PubMed

Affiliation: Department of Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2, Tomogaoka, Suma-ku, Kobe, 654-0142, Japan.

ABSTRACT
The aim of the study was to identify a set of discriminating genes that could be used for the prediction of Lymph node (LN) metastasis in human colorectal cancer (CRC), and for this, we compared the whole genome profiles of two CRC cell lines (the primary cell line SW480 and its LN metastatic variant, SW620) and identified eight genes [S100 calcium-binding protein P; aldo-keto reductase family 1(AKR1), member B1 (aldose reductase; AKR1B1); AKR1, member C3 (AKR1C3); calponin 3, acidic; metastasis associated in colon cancer 1; hemoglobin, epsilon 1; trefoil factor 3; and FGGY carbohydrate kinase domain containing]. These genes were examined by quantitative RT-PCR in tissues and LNs in 14 CRC patients and 11 control patients. The level of AKR1C3 mRNA expression was significantly different between the Dukes' stage A, B, and C groups and the control group (p < 0.05, p < 0.001, and p < 0.001) and was also significantly different between Dukes' stage C and A or B groups (p < 0.05 and p < 0.001, respectively). The expression of CNN3 was significantly different between the Dukes' stage C and B or control groups (p < 0.001 and p < 0.01, respectively). There were significant correlations between the expression levels of AKR1C3 and CNN3. AKR1C3 and CNN3 expressions are more accurate and suitable markers for the diagnosis of LN metastasis than the other six genes examined in this study.

No MeSH data available.


Related in: MedlinePlus