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Alterations in expression profile of iron-related genes in colorectal cancer.

Hamara K, Bielecka-Kowalska A, Przybylowska-Sygut K, Sygut A, Dziki A, Szemraj J - Mol. Biol. Rep. (2013)

Bottom Line: For the first time we have shown, that ferroportin concentration is significantly associated with miR-194 level, causing the reduction of this transporter amount in tumor tissues of patients with more advanced stages of CRC.We have also shown the alterations in expressing profile of miR-31, miR-133a, miR-141, miR-145, miR-149, miR-182 and miR-194, which were observed even in the early stage of disease, and identified a set of genes, which take place in correct assigning of patients in dependence of CRC stage.These iron-related genes could become potential diagnostic or prognostic indicators for patients with CRC.

View Article: PubMed Central - PubMed

ABSTRACT
Iron can play a role in colorectal cancer (CRC) development. The expression of genes involved in iron metabolism and its regulation in CRC has not been investigated well. Also the correlation between the level of iron-related genes expression and cancer progression is not known. In this study we collected paired samples of primary adenocarcinoma and adjacent normal mucosa from 73 patients. We assessed the mRNA or miRNA levels of 21 genes and verify their association with clinicopathological characteristics of CRC patients. Our experiments revealed, that the level of divalent metal transporter 1 transcript is well correlated with mRNA levels of iron regulatory proteins (IRPs) in tumor specimens. We have shown, that IRP2 can also be engaged in the mRNA stabilization of other iron transporter-transferrin receptor 1 (TfR1) in early stage of disease, however, in more advanced stages of CRC, mRNA level of TfR1 is related to miR-31 level. For the first time we have shown, that ferroportin concentration is significantly associated with miR-194 level, causing the reduction of this transporter amount in tumor tissues of patients with more advanced stages of CRC. We have also shown the alterations in expressing profile of miR-31, miR-133a, miR-141, miR-145, miR-149, miR-182 and miR-194, which were observed even in the early stage of disease, and identified a set of genes, which take place in correct assigning of patients in dependence of CRC stage. These iron-related genes could become potential diagnostic or prognostic indicators for patients with CRC.

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Discriminant analysis of patients a in various stages of CRC, according to pTNM system or b with different diagnosis of cancer. a In this model 7 variables were used (DMT1, HAMP, TfR2, miR-31, miR-149, miR-182, miR-194); Wilks’ lambda was 0.006, p < 0.0001, n = 71; Stage I (circles), Stage IIA (diamonds), Stages IIIA + IIIB (squares), Stages IIIC + IV (triangles). b In this model 9 variables were used (DMT1, IRP1, IRP2, Tf, miR-31, miR-133a, miR-145, miR-149, miR-194); Wilks’ lambda was 0.046, p < 0.0006, n = 73; Adenocarcinoma tubulare (circles), Adenocarcinoma tubulare/mucinosum (squares), Adenocarcinoma mucinosum (diamonds)
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Fig4: Discriminant analysis of patients a in various stages of CRC, according to pTNM system or b with different diagnosis of cancer. a In this model 7 variables were used (DMT1, HAMP, TfR2, miR-31, miR-149, miR-182, miR-194); Wilks’ lambda was 0.006, p < 0.0001, n = 71; Stage I (circles), Stage IIA (diamonds), Stages IIIA + IIIB (squares), Stages IIIC + IV (triangles). b In this model 9 variables were used (DMT1, IRP1, IRP2, Tf, miR-31, miR-133a, miR-145, miR-149, miR-194); Wilks’ lambda was 0.046, p < 0.0006, n = 73; Adenocarcinoma tubulare (circles), Adenocarcinoma tubulare/mucinosum (squares), Adenocarcinoma mucinosum (diamonds)

Mentions: To identify genes, which can play a role in progression of colorectal adenocarcinoma or discrimination of CRC patients in dependence on clinicopathological characteristics, we conducted discriminant analysis of iron-related gene expression. The forward stepwise mode constructed discriminant functions including all genes under study, and showed that DMT1, HAMP, TfR2, miR-31, miR-149, miR-182, miR-194 were the most significant parameters responsible for progression of colorectal adenocarcinoma, assigning all cases correctly (p < 0.0001). Fig. 4a shows that the alterations in expression of chosen genes can distinguish patients with the wide spectrum of cancer stages.Fig. 4


Alterations in expression profile of iron-related genes in colorectal cancer.

Hamara K, Bielecka-Kowalska A, Przybylowska-Sygut K, Sygut A, Dziki A, Szemraj J - Mol. Biol. Rep. (2013)

Discriminant analysis of patients a in various stages of CRC, according to pTNM system or b with different diagnosis of cancer. a In this model 7 variables were used (DMT1, HAMP, TfR2, miR-31, miR-149, miR-182, miR-194); Wilks’ lambda was 0.006, p < 0.0001, n = 71; Stage I (circles), Stage IIA (diamonds), Stages IIIA + IIIB (squares), Stages IIIC + IV (triangles). b In this model 9 variables were used (DMT1, IRP1, IRP2, Tf, miR-31, miR-133a, miR-145, miR-149, miR-194); Wilks’ lambda was 0.046, p < 0.0006, n = 73; Adenocarcinoma tubulare (circles), Adenocarcinoma tubulare/mucinosum (squares), Adenocarcinoma mucinosum (diamonds)
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Related In: Results  -  Collection

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Fig4: Discriminant analysis of patients a in various stages of CRC, according to pTNM system or b with different diagnosis of cancer. a In this model 7 variables were used (DMT1, HAMP, TfR2, miR-31, miR-149, miR-182, miR-194); Wilks’ lambda was 0.006, p < 0.0001, n = 71; Stage I (circles), Stage IIA (diamonds), Stages IIIA + IIIB (squares), Stages IIIC + IV (triangles). b In this model 9 variables were used (DMT1, IRP1, IRP2, Tf, miR-31, miR-133a, miR-145, miR-149, miR-194); Wilks’ lambda was 0.046, p < 0.0006, n = 73; Adenocarcinoma tubulare (circles), Adenocarcinoma tubulare/mucinosum (squares), Adenocarcinoma mucinosum (diamonds)
Mentions: To identify genes, which can play a role in progression of colorectal adenocarcinoma or discrimination of CRC patients in dependence on clinicopathological characteristics, we conducted discriminant analysis of iron-related gene expression. The forward stepwise mode constructed discriminant functions including all genes under study, and showed that DMT1, HAMP, TfR2, miR-31, miR-149, miR-182, miR-194 were the most significant parameters responsible for progression of colorectal adenocarcinoma, assigning all cases correctly (p < 0.0001). Fig. 4a shows that the alterations in expression of chosen genes can distinguish patients with the wide spectrum of cancer stages.Fig. 4

Bottom Line: For the first time we have shown, that ferroportin concentration is significantly associated with miR-194 level, causing the reduction of this transporter amount in tumor tissues of patients with more advanced stages of CRC.We have also shown the alterations in expressing profile of miR-31, miR-133a, miR-141, miR-145, miR-149, miR-182 and miR-194, which were observed even in the early stage of disease, and identified a set of genes, which take place in correct assigning of patients in dependence of CRC stage.These iron-related genes could become potential diagnostic or prognostic indicators for patients with CRC.

View Article: PubMed Central - PubMed

ABSTRACT
Iron can play a role in colorectal cancer (CRC) development. The expression of genes involved in iron metabolism and its regulation in CRC has not been investigated well. Also the correlation between the level of iron-related genes expression and cancer progression is not known. In this study we collected paired samples of primary adenocarcinoma and adjacent normal mucosa from 73 patients. We assessed the mRNA or miRNA levels of 21 genes and verify their association with clinicopathological characteristics of CRC patients. Our experiments revealed, that the level of divalent metal transporter 1 transcript is well correlated with mRNA levels of iron regulatory proteins (IRPs) in tumor specimens. We have shown, that IRP2 can also be engaged in the mRNA stabilization of other iron transporter-transferrin receptor 1 (TfR1) in early stage of disease, however, in more advanced stages of CRC, mRNA level of TfR1 is related to miR-31 level. For the first time we have shown, that ferroportin concentration is significantly associated with miR-194 level, causing the reduction of this transporter amount in tumor tissues of patients with more advanced stages of CRC. We have also shown the alterations in expressing profile of miR-31, miR-133a, miR-141, miR-145, miR-149, miR-182 and miR-194, which were observed even in the early stage of disease, and identified a set of genes, which take place in correct assigning of patients in dependence of CRC stage. These iron-related genes could become potential diagnostic or prognostic indicators for patients with CRC.

Show MeSH
Related in: MedlinePlus