Comparison of matrix proteinase mRNA expression in morphologically normal, neoplastic, and metastatic colon tissue and colon biopsies from healthy donors

Abstract

Matrix metalloproteinases (MMPs) responsible for the extracellular matrix remodeling, the activation of various growth factors, and angiogenesis play an important role in the colorectal cancer (CRC) development. In the present work the comparative analysis of MMP-7, -8, -9, and -11 mRNA as well mRNA of the Ki-67 proliferation marker in tissue samples obtained from CRC patients and healthy individuals. Employing the real time PCR method the expression levels of several MMPs (MMP-7, -8, -9, and -11) and cell proliferation marker, Ki-67, were simultaneously measured in 256 tissue samples obtained from 112 patients with CRC: 112 samples of the primary tumor (CRC), 112 samples of the most distant border of morphologically normal colonic mucosa (MNT), 16 samples of liver metastases) and from 16 healthy volunteers who underwent colonoscopy and biopsy. The expression of both MMPs studied and Ki-67 was found to be elevated in CRC primary tumors and liver metastases compared with the normal mucosa. CRC tumor and metastatic cells exhibited similar proliferative activity. The metastases are characterized by the highest cross-correlation of MMPs among tissue types tested. For the first time it was shown that normal mucosa from healthy individuals and CRC patients varied in the MMP-8 expression level. They also had dissimilar MMP correlation patterns thus suggesting that epithelial cells adjusted to CRC tumor differ from mucosal epithelial cells of healthy individuals.

Differentially expressed lncRNAs and mRNAs identified by NGS analysis in colorectal cancer patients

“…This suggests that the influence of these mRNAs on cell components might be related to mitosis. It is well known that mitosis is an important process for cell proliferation . Therefore, we conclude that these upregulated mRNA in colorectal cancer may make mitosis‐related cell components abnormal in result or function by different ways.…”

“…It is well known that mitosis is an important process for cell proliferation. 12 Therefore, we conclude that these upregulated mRNA in colorectal cancer may make mitosis-related cell components abnormal in result or function by different ways. In addition, cell cycle regulation is of great significance for maintaining the homeostasis of the body and preventing the occurrence of cancer.…”

“…Enrichment analysis also showed that these mRNAs are mainly associated with the components of extracellular matrix, suggesting that activation of the extracellular matrix plays a key role in the process of CRC. Many studies have found that a large number of factors involved in this process are produced in colorectal cancer tissue . The proliferation, differentiation, and invasion capabilities of tumor cells are regulated by various molecules.…”

“…Many studies have found that a large number of factors involved in this process are produced in colorectal cancer tissue. 12 The proliferation, differentiation, and invasion capabilities of tumor cells are regulated by various molecules. We also found that the mRNAs are mainly related to the chromosome, spindle, and centromeric regions, and thus mitosis.…”

The study of mRNA expression profiles of main cell function regulator genes in unchanged colonic mucosa from healthy donors

“…В настоящее время в большинстве исследований при изучении патологических процессов в качестве контрольных образцов используют ткани без морфологических признаков заболевания, часто полученные из резецированного участка поражённого органа. В то же время в ряде работ [11][12][13][14] подчеркивается, что край резекции нельзя считать нормальной тканью, так как при развитии злокачественного процесса в отдалённых от опухоли участках пораженного органа обнаруживаются молекулярные изменения. В наших предыдущих исследованиях [13,14] также показано, что морфологически неизмененная ткань ТК на расстоянии 15-20 см от опухоли демонстрирует глубокие отличия в уровне экспрессии ряда генов по сравнению с тем же отделом ТК здоровых людей.…”