Limits...
Circulating miR-182 is a biomarker of colorectal adenocarcinoma progression.

Perilli L, Vicentini C, Agostini M, Pizzini S, Pizzi M, D'Angelo E, Bortoluzzi S, Mandruzzato S, Mammano E, Rugge M, Nitti D, Scarpa A, Fassan M, Zanovello P - Oncotarget (2014)

Bottom Line: Plasma miR-182 concentrations were significantly higher in CRC patients than in healthy controls or patients with colon polyps at endoscopy.Moreover, miR-182 plasma levels were significantly reduced in post-operative samples after radical hepatic metastasectomy compared to preoperative samples.Our results strengthen the hypothesis of a central role of miR-182 dysregulation in colon mucosa transformation, demonstrate the concomitant progressive down-regulation of ENTPD5 levels during colon carcinogenesis, and indicate the potential of circulating miR-182 as blood based biomarker for screening and monitoring CRC during the follow-up.

View Article: PubMed Central - PubMed

Affiliation: Oncology and Immunology Section, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; These authors contributed equally to this work.

ABSTRACT
MiR-182 expression was evaluated by qRT-PCR and in situ hybridization in 20 tubular adenomas, 50 colorectal carcinoma (CRC), and 40 CRC liver metastases. Control samples obtained from patients with irritable bowel syndrome, or tumor-matched normal colon mucosa were analyzed (n=50). MiR-182 expression increased progressively and significantly along with the colorectal carcinogenesis cascade, and in CRC liver metastases. The inverse relation between miR-182 and the expression of its target gene ENTPD5 was investigated by immunohistochemical analysis. We observed that normal colocytes featured a strong ENTPD5 cytoplasmic expression whereas a significantly and progressively lower expression was present along with dedifferentiation of the histologic phenotype. Plasma samples from 51 CRC patients and controls were tested for miR-182 expression. Plasma miR-182 concentrations were significantly higher in CRC patients than in healthy controls or patients with colon polyps at endoscopy. Moreover, miR-182 plasma levels were significantly reduced in post-operative samples after radical hepatic metastasectomy compared to preoperative samples. Our results strengthen the hypothesis of a central role of miR-182 dysregulation in colon mucosa transformation, demonstrate the concomitant progressive down-regulation of ENTPD5 levels during colon carcinogenesis, and indicate the potential of circulating miR-182 as blood based biomarker for screening and monitoring CRC during the follow-up.

Show MeSH

Related in: MedlinePlus

miR-182 is up-regulated during colon carcinogenesis(A) miR-182 expression was evaluated by qRT-PCR after RNA extraction from FFPE samples of colon normal mucosa, LG-IEN, HG-IEN lesions and CRCs. (B) miR-182 expression was evaluated by qRT-PCR in matched surgical samples of normal colon mucosa, primary CRC and liver metastatis. (C) Representative ISH evaluation of miR-182 in matched tissue sections of normal colon, primary tumor and metastatic CRC (N= normal colon mucosa; K= primary CRC). The presence of miR-182 is shown by a grainy blue cytoplasmic stain; slides counterstained in fast red. (Original magnifications 10x and 20x). Significance (Student's t test); *p<0.05; **p<0.01. nRQ, normalized Relative Quantity. Data were expressed as mean values ± SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4196150&req=5

Figure 1: miR-182 is up-regulated during colon carcinogenesis(A) miR-182 expression was evaluated by qRT-PCR after RNA extraction from FFPE samples of colon normal mucosa, LG-IEN, HG-IEN lesions and CRCs. (B) miR-182 expression was evaluated by qRT-PCR in matched surgical samples of normal colon mucosa, primary CRC and liver metastatis. (C) Representative ISH evaluation of miR-182 in matched tissue sections of normal colon, primary tumor and metastatic CRC (N= normal colon mucosa; K= primary CRC). The presence of miR-182 is shown by a grainy blue cytoplasmic stain; slides counterstained in fast red. (Original magnifications 10x and 20x). Significance (Student's t test); *p<0.05; **p<0.01. nRQ, normalized Relative Quantity. Data were expressed as mean values ± SD.

Mentions: To extend our previous findings on high miR-182 expression in CRC [24], we investigated its expressions in the colic adenoma-carcinoma sequence. To this aim, miR-182 expression was analyzed by qRT-PCR in a series of FFPE samples including 10 normal colic mucosa, 20 tubular adenomas low-grade [LG] and high-grade [HG] intraepithelial neoplasia [IEN, formerly known as dysplasia], and 10 early primary stages CRC. We observed a significant up-regulation of miR-182 in tubular adenomas with LG-IEN (2.35-fold change; t-test, p=0.006), tubular adenomas with HG-IEN (4.63-fold change; t-test, p=0.030), and in CRCs (15.2-fold change; t-test, p=0.020) (Figure 1A) in comparison to normal colic mucosa. Overall, miR-182 expression increased progressively and significantly along with the carcinogenesis cascade (ANOVA, p<0.001).


Circulating miR-182 is a biomarker of colorectal adenocarcinoma progression.

Perilli L, Vicentini C, Agostini M, Pizzini S, Pizzi M, D'Angelo E, Bortoluzzi S, Mandruzzato S, Mammano E, Rugge M, Nitti D, Scarpa A, Fassan M, Zanovello P - Oncotarget (2014)

miR-182 is up-regulated during colon carcinogenesis(A) miR-182 expression was evaluated by qRT-PCR after RNA extraction from FFPE samples of colon normal mucosa, LG-IEN, HG-IEN lesions and CRCs. (B) miR-182 expression was evaluated by qRT-PCR in matched surgical samples of normal colon mucosa, primary CRC and liver metastatis. (C) Representative ISH evaluation of miR-182 in matched tissue sections of normal colon, primary tumor and metastatic CRC (N= normal colon mucosa; K= primary CRC). The presence of miR-182 is shown by a grainy blue cytoplasmic stain; slides counterstained in fast red. (Original magnifications 10x and 20x). Significance (Student's t test); *p<0.05; **p<0.01. nRQ, normalized Relative Quantity. Data were expressed as mean values ± SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4196150&req=5

Figure 1: miR-182 is up-regulated during colon carcinogenesis(A) miR-182 expression was evaluated by qRT-PCR after RNA extraction from FFPE samples of colon normal mucosa, LG-IEN, HG-IEN lesions and CRCs. (B) miR-182 expression was evaluated by qRT-PCR in matched surgical samples of normal colon mucosa, primary CRC and liver metastatis. (C) Representative ISH evaluation of miR-182 in matched tissue sections of normal colon, primary tumor and metastatic CRC (N= normal colon mucosa; K= primary CRC). The presence of miR-182 is shown by a grainy blue cytoplasmic stain; slides counterstained in fast red. (Original magnifications 10x and 20x). Significance (Student's t test); *p<0.05; **p<0.01. nRQ, normalized Relative Quantity. Data were expressed as mean values ± SD.
Mentions: To extend our previous findings on high miR-182 expression in CRC [24], we investigated its expressions in the colic adenoma-carcinoma sequence. To this aim, miR-182 expression was analyzed by qRT-PCR in a series of FFPE samples including 10 normal colic mucosa, 20 tubular adenomas low-grade [LG] and high-grade [HG] intraepithelial neoplasia [IEN, formerly known as dysplasia], and 10 early primary stages CRC. We observed a significant up-regulation of miR-182 in tubular adenomas with LG-IEN (2.35-fold change; t-test, p=0.006), tubular adenomas with HG-IEN (4.63-fold change; t-test, p=0.030), and in CRCs (15.2-fold change; t-test, p=0.020) (Figure 1A) in comparison to normal colic mucosa. Overall, miR-182 expression increased progressively and significantly along with the carcinogenesis cascade (ANOVA, p<0.001).

Bottom Line: Plasma miR-182 concentrations were significantly higher in CRC patients than in healthy controls or patients with colon polyps at endoscopy.Moreover, miR-182 plasma levels were significantly reduced in post-operative samples after radical hepatic metastasectomy compared to preoperative samples.Our results strengthen the hypothesis of a central role of miR-182 dysregulation in colon mucosa transformation, demonstrate the concomitant progressive down-regulation of ENTPD5 levels during colon carcinogenesis, and indicate the potential of circulating miR-182 as blood based biomarker for screening and monitoring CRC during the follow-up.

View Article: PubMed Central - PubMed

Affiliation: Oncology and Immunology Section, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; These authors contributed equally to this work.

ABSTRACT
MiR-182 expression was evaluated by qRT-PCR and in situ hybridization in 20 tubular adenomas, 50 colorectal carcinoma (CRC), and 40 CRC liver metastases. Control samples obtained from patients with irritable bowel syndrome, or tumor-matched normal colon mucosa were analyzed (n=50). MiR-182 expression increased progressively and significantly along with the colorectal carcinogenesis cascade, and in CRC liver metastases. The inverse relation between miR-182 and the expression of its target gene ENTPD5 was investigated by immunohistochemical analysis. We observed that normal colocytes featured a strong ENTPD5 cytoplasmic expression whereas a significantly and progressively lower expression was present along with dedifferentiation of the histologic phenotype. Plasma samples from 51 CRC patients and controls were tested for miR-182 expression. Plasma miR-182 concentrations were significantly higher in CRC patients than in healthy controls or patients with colon polyps at endoscopy. Moreover, miR-182 plasma levels were significantly reduced in post-operative samples after radical hepatic metastasectomy compared to preoperative samples. Our results strengthen the hypothesis of a central role of miR-182 dysregulation in colon mucosa transformation, demonstrate the concomitant progressive down-regulation of ENTPD5 levels during colon carcinogenesis, and indicate the potential of circulating miR-182 as blood based biomarker for screening and monitoring CRC during the follow-up.

Show MeSH
Related in: MedlinePlus