Disseminated Tumor Cells in Bone Marrow of Gastric Cancer Patients: Correlation with Tumor Hypoxia and Clinical Relevance

Abstract

Aim. The evaluation of the clinical relevance of disseminated tumor cells (DTCs) in bone marrow (BM) of patients with gastric cancer (GC) and their association with primary tumor hypoxia. Patients and Methods. 89 resected specimens were used. DTCs were detected using immunocytochemistry, the level of tumor hypoxia using NMR spectroscopy, CD68, CD34, VEGF, and VEGFR-1 (Flt-1) expression using immunohistochemistry, and MMP-2 and MMP-9 activity using zymography. Results. DTCs were detected in 51.4% of GC patients with M0. There was significant correlation between frequency of DTCs in BM and level of tumor hypoxia (P < 0.024). DTCs presence was accompanied with Flt-1 positivity of BM. The correlation between DTCs and tumor VEGF expression in patients with M0 was shown (P < 0.0248). Activity of MMP-2 and MMP-9 in BM was linked with DTCs in patients with M0 (P < 0.05). Overall survival (OS) of patients with M0 and DTCs was shorter than that of patients without DTCs (patients in both groups were operated only) (P = 0.0497). Conclusion. Appearance of DTCs correlates with hypoxia level in primary tumors. Detection of DTCs in GC patients may be relevant indicator for adjuvant chemotherapy using.

RETRACTED ARTICLE: Functional studies of miR-130a on the inhibitory pathways of apoptosis in patients with chronic myeloid leukemia

“…Furthermore, some miRNA-encoding genes have been classified as oncogenic or tumor suppressive genes according to their function in cellular transformation and altered expression in tumors. [11][12][13] Tumor suppressive miRNAs may function by downregulating the products of proto-oncogenes. For example, the miRNA family let-7 targets expression of the oncogenes KRAS, NRAS and HMGA2 and its expression is diminished in lung tumors.…”

“…The recognition that negative growth control, including growth arrest and programmed cell death, must be understood to comprehend how appropriate cell numbers are maintained and how alterations in any part of the equation can contribute to malignancy has led to a burst of work in this field. 9,10 MicroRNAs are an extensive class of small noncoding RNAs (18-25 nt), with a significant impact on a number of biological processes, including development, differentiation, growth, metabolism and tumorigenesis, 11 through direct binding to the 3′ un-translational region (3′-UTR) of target mRNAs. MicroRNAs can regulate gene expression by two modes, depending on the degree of complementarity with the mRNA targets, to suppress translation or induce mRNA degradation.…”

CXCR4 Expression in Gastric Cancer and Bone Marrow: Association with Hypoxia-Regulated Indices, Disseminated Tumor Cells, and Patients Survival

“…The last finding may be discussed in the context of predisposition of BM to be a new site for tumor cells by CXCR4 expression. It may be noted that DTCs in bone marrow were detected in 51.4% of gastric cancer patients with M 0 category as was published recently [37].…”

The hypoxia-inducible factor-1α in stemness and resistance to chemotherapy in gastric cancer: Future directions for therapeutic targeting

“…Hypoxia was also detected in the normal gastric mucosa in most gastric cancer patients and displayed a high correlation with decreased overall survival ( Bubnovskaya et al, 2014a ). Furthermore, gastric tumors with moderate to severe hypoxia are associated with an increased risk of bone metastasis and mortality, even in patients with non-metastatic local tumors ( Bubnovskaya et al, 2014b ; Bubnovskaya and Osinsky, 2020 ).…”