Early detection of tumor cells in bone marrow and peripheral blood in a fast‑progressing gastric cancer model

Abstract

Helicobacter pylori (H. pylori) infection is a major risk factor for the development of gastric cancer. The authors previously demonstrated that in mice deficient in myeloid differentiation primary response 88 (Myd88 -/-), infection with Helicobacter felis (H. felis) a close relative of H. pylori, subsequently rapidly progressed to neoplasia. The present study examined circulating tumor cells (CTCs) by measuring the expression of cytokeratins, epithelial-to-mesenchymal transition (EMT)-related markers and cancer stem cell (CSC) markers in bone marrow and peripheral blood from Myd88 -/and wild-type (WT) mice. Cytokeratins CK8/18 were detected as early as 4 months post-infection in Myd88 -/mice. By contrast, cytokeratins were not detected in WT mice even after 7 months post-infection. The expression of Mucin-1 (MUC1) was observed in both bone marrow and peripheral blood at different time points, suggesting its role in gastric cancer metastasis. Snail, Twist and ZEB were expressed at different levels in bone marrow and peripheral blood. The expression of these EMT-related markers suggests the manifestation of cancer metastasis in the early stages of disease development.LGR5, CD44 and CD133 were the most prominent CSC markers detected. The detection of CSC and EMT markers along with cytokeratins does reinforce their use as biomarkers for gastric cancer metastasis. This early detection of markers suggests that CTCs leave primary site even before cancer is well established. Thus, cytokeratins, EMT, and CSCs could be used as biomarkers to detect aggressive forms of gastric cancers. This information may prove to be of significance in stratifying patients for treatment prior to the onset of severe disease-related characteristics.

Prognostic value and potential molecular mechanism of the like-Sm gene family in early-stage pancreatic ductal adenocarcinoma

“…However, CA19-9 is insufficient as an independent diagnostic tool; for instance, serum CA19-9 elevation can occur in patients with benign diseases such as chronic or acute pancreatitis, cholangitis, obstructive jaundice, liver cirrhosis, or other malignancies such as gastrointestinal cancers ( 29 ). CTCs are derived from primary tumors or metastatic sites and circulate in the bloodstream, and portal vein blood CTC counts but not peripheral blood CTC counts are correlated with OS ( 30 ). Neutrophil gelatinase-associated lipocalin requires numerous samples and multi-center clinical trials to identify and verify urinary diagnostic biomarkers of PDAC ( 28 ).…”

DNA methylation drives a new path in gastric cancer early detection: Current impact and prospects

“…The peripheral blood can provide real-time information from tumors rich in leucocytes. 94 Leukocytes are considered the first line of defense in the immune system against cancer, and they first cause changes in the epigenetic characteristics of peripheral leukocytes during immunoediting once tumorigenesis occurs. 95 Therefore, changes in the epigenetic characteristics of leukocytes can directly reflect the immune response triggered by tumorigenesis and progression.…”

Genomically Silent Refractory Gastric Cancer in a Young Patient Exhibits Overexpression of CXCL5

“…The goal was to further understand the status of the disease, either indicating the extent of disease severity/malignancy or host immunity to the tumor. Total RNA was isolated from the patient’s gastric cancer tissue and processed for quantitative real-time polymerase chain reaction (qRT-PCR), as described in our previous studies [ 21 , 22 , 23 , 24 ], using the Direct-zol RNA mini kit (Zymo Research Corp) according to the manufacturer’s instructions. RNA quality was determined by using a Nanodrop system (Thermo Fisher Scientific, Inc., Waltham, MA, USA) followed by reverse transcription into cDNA using the High Capacity cDNA Reverse Transcription kit (Thermo Fisher Scientific, Inc.).…”