Cancer Biomarkers - Volume 41, issue 2

Authors: Liang, Wenjuan | Wang, Haiyan | Hong, Lijuan | Cao, Wenting | Chen, Shuaiyin | Zhang, Rongguang

Article Type: Research Article

Abstract: BACKGROUND: The association between infection with cagA -positive H. pylori and an elevated susceptibility to gastric cancer has been firmly established. PIM2 is known to be overexpressed in various types of cancers; however, the specific mechanism by which cagA influences the regulation of PIM2 expression in gastric cancer remains unidentified at present. MATERIALS AND METHODS: A mutant NCTC11637Δ cagA strain of H. pylori and the eukaryotic expression vector pcDNA-cagA were constructed for evaluating PIM2 expression levels in gastric cancer cells (HGC27, SGC7901, and AG) co-cultured with the NCTC11637 and NCTC11637Δ …cagA strain, as well as pcDNA-cagA and the empty vector pcDNA3.1 (+ ). RESULTS: Co-culturing gastric cancer cells with NCTC11637 significantly increased PIM2 expression levels (P < 0.001) compared to the negative control group. Additionally, the expression of PIM2 in cells co-cultured with NCTC11637 was higher than that co-cultured with NCTC11637Δ cagA (P < 0.001). Furthermore, successful construction of the eukaryotic expression vector pcDNA-cagA resulted in a significant increase in PIM2 mRNA expression levels after its transfection into gastric cancer cells compared to the control group after 48 hours. CONCLUSIONS: The findings indicate that H. pylori /cagA A could be one of the key factors in regulating PIM2 expression levels, potentially influencing the progression of H. pylori -related Gastric Cancer. Show more

Keywords: Gastric cancer, PIM2, Helicobacter pylori, CagA, regulation

DOI: 10.3233/CBM-230351

Citation: Cancer Biomarkers, vol. 41, no. 2, pp. 93-101, 2024

Authors: Li, Zhengtai | Li, Hongjiang | Fang, Kun | Lin, Xinglei | Yu, Changyuan

Article Type: Research Article

Abstract: BACKGROUND: Endogenous retroviruses, previously deemed “junk” DNA, have gained attention in recent scientific studies. These inherited genomic elements are now recognized for their potential roles in diseases, especially cancer, highlighting their value as potential diagnostic or therapeutic targets. OBJECTIVE: This research aims to explore the association between human endogenous retroviruses (HERV) and gastric cancer, focusing on discerning HERV expression patterns and understanding their implications in gastric cancer pathology. METHODS: A quantitative analysis of HERV expression was conducted, employing Support Vector Machine (SVM) and AdaBoost algorithms to identify discriminative HERVs. The co-regulation network between …protein-coding genes and HERVs was constructed using the Weighted Gene Co-expression Network Analysis (WGCNA). RESULTS: Three distinct HERVs (LTR16A| 72| 451, LTR91| 636| 874, LTR27D| 87| 222) were identified as significantly different. Strong correlations were found between HERVs, and gene sets enriched in the inflammatory pathway. CONCLUSIONS: HERVs appear to influence abnormal inflammatory responses, suggesting a pivotal role in gastric cancer development. Show more

Keywords: Human endogenous retroviruses, machine learning, WGCNA, Gastric cancer

DOI: 10.3233/CBM-230417

Citation: Cancer Biomarkers, vol. 41, no. 2, pp. 103-113, 2024

Authors: Giorello, María Belén | Borzone, Francisco Raúl | Mora, María Florencia | Padin, María del Rosario | Wernicke, Alejandra | Labovsky, Vivian | Chasseing, Norma Alejandra

Article Type: Research Article

Abstract: BACKGROUND: The molecular system of receptor activator of nuclear factor kappa-β (RANK) and its ligand (RANKL) plays a role in a variety of physiological and pathological processes. These encompass the regulation of bone metabolism, mammary gland development, immune function, as well as their involvement and tumorigenesis. Nevertheless, limited knowledge exists regarding their function within the tumor microenvironment. METHODS AND RESULTS: We explored the significance of RANK expression in cancer-associated fibroblasts (CAFs) as a prognostic biomarker in early breast cancer patients (BCPs) by immunohistochemistry. Results reveal a significant correlation between high RANK expression in …CAFs and an increased risk of metastasis (p = 0.006), shorter metastasis-free survival (MFS) [p = 0.007, OR (95%CI) = 2.290 (1.259–4.156)], and lower overall survival (OS) [p = 0.004, OR (95%CI) = 2.469 (1.343–4.541)]. Upon analyzing the phenotype of CD34(-) CAFs isolated from primary tumors in BCPs, we observed co-expression of RANK with CD105 marker by immunofluorescence and flow cytometry, characteristic of mesenchymal stem/stromal cells (MSCs), suggesting the possible cellular origin. Also RANKL-RANK system increase the OCT-4, SOX-2 and DKK-1 (dickkopf 1) gene expression in CD34(-) CAFs by RT-PCR. Moreover, this system plays a crucial role in the migration of these CD34(-) CAFs. CONCLUSIONS: These results support the clinical relevance of RANK in CAFs and propose its potential as a future therapeutic target in the treatment of early BCPs. Show more

Keywords: Cancer-associated fibroblasts, RANK/RANKL, breast cancer, prognostic factor, metastatic occurrence

DOI: 10.3233/CBM-230523

Citation: Cancer Biomarkers, vol. 41, no. 2, pp. 115-132, 2024

Authors: Deng, Yuanhong | Fu, Ying | Feng, Ganghua | Zhang, Yi

Article Type: Research Article

Abstract: BACKGROUND: Radioiodine-131 (I-131) therapy is the common postoperative adjuvant therapy for differentiated thyroid cancer (DTC) However, methods to evaluate the efficacy and toxicity of I-131 on DTC are still lacking. OBJECTIVE: To evaluate the association between vitamin D receptor (VDR) gene polymorphisms and the efficacy and toxicity of I-131 in DTC patients. METHODS: A total of 256 DTC patients who received I-131 therapy were enrolled. The patients were divided into effective group and ineffective group. 4 single nucleotide polymorphisms (SNPs) (rs7975232, rs731236, rs1544410 and rs10735810) of VDR were analyzed by polymerase chain reaction-restriction …fragment length polymorphism (PCR-RFLP) Cell counting kit-8 (CCK-8) and flow cytometry were used to detect the proliferation and apoptosis of thyroid cancer cells. RESULTS: Patients in effective group had more CC genotype of rs7975232 and GG genotype of rs10735810 compared with patients in ineffective group They were also independent factors for influencing the efficacy of I-131. PTC-1 and FTC-133 cells transfected with CC genotype of rs7975232 showed lower proliferative activity and higher apoptosis rate after being treated with I-131 In addition, patients with CC genotype at rs7975232 had fewer adverse reactions after I-131 treatment. CONCLUSIONS: VDR gene polymorphisms may be associated with the efficacy and toxicity of I-131 in DTC patients, which will help to personalize the treatment for patients. Show more

Keywords: Differentiated thyroid cancer, Vitamin D receptor, polymorphism, radioiodine-131, efficacy

DOI: 10.3233/CBM-230566

Citation: Cancer Biomarkers, vol. 41, no. 2, pp. 133-143, 2024

Authors: Daiki, Kentaro | Kanada, Yoko | Nagata, Aya | Taruno, Kanae | Igarashi, Katsuhide | Yamochi, Toshiko | Ota, Hirotaka | Sato, Fumiaki | Nakamura, Seigo | Kato, Yoshinori

Article Type: Research Article

Abstract: BACKGROUND: Endocan was reported to affect breast cancer patients negatively and was able to be detected from patients’ blood. OBJECTIVE: This study aimed to investigate if the measurement of blood endocan in breast cancer patients with high ESM1 expression could be an effective tool to detect postoperative recurrence compared with existing tumor markers. METHODS: Blood was collected before and after the tumor resection from the mouse models of breast cancer, and endocan levels were measured while visualizing metastatic recurrence with noninvasive luminescence imaging. In clinical settings, blood was withdrawn from 16 breast …cancer patients before and after the tumor resection, and the effect of lumpectomy on blood endocan level was evaluated. Additionally, the blood endocan from 20 patients diagnosed with postoperative recurrence was measured, and their positivity rate for endocan was compared with that for serum carcinoembryonic antigen (CEA) or cancer antigen 15-3 (CA15-3). RESULTS: Our preclinical and clinical experiments revealed that blood endocan levels reflected tumor burden. Furthermore, over 60% of patients suffering from postoperative recurrence who tested negative for CEA or CA15-3 were positive for endocan. CONCLUSIONS: Our results support the clinical significance of endocan in breast cancer patients for detecting breast cancer recurrence. Show more

Keywords: Endocan, recurrence, biomarker, animal models, clinical study

DOI: 10.3233/CBM-240034

Citation: Cancer Biomarkers, vol. 41, no. 2, pp. 145-154, 2024

Authors: Alhamawi, Renad M. | Aloufi, Noof | Alamri, Abeer F. | Altubayli, Fatima A. | Alsairi, Raghad T. | Alhamad, Reem A. | Alharbi, Shouq M. | Ankhli, Zainab A. | Eid, Hamza M. A. | Almutawif, Yahya A.

Article Type: Research Article

Abstract: BACKGROUND: Invariant natural killer T (iNKT) cells are an immune subset that purportedly link the adaptive and the innate arms of the immune system. Importantly, iNKT cells contribute to anti-cancer immunity in different types of hematological and solid malignancies by secreting pro-inflammatory cytokines. Therefore, using such cells in treating different type of tumors would be an ideal candidate for cancer immunotherapy. OBJECTIVE: To assess the prognostic effect of iNKT cells across different types of solid and hematological tumors. METHODS: In systematic review and meta-analysis, articles assessed the prognostic effect of iNKT cells were …systemically searched using the scientific databases including Google Scholar, ScienceDirect, PubMed, Cochrane Central, and Scopus. RESULTS: Strikingly, the analysis showed the positive impact of intratumoral or circulating iNKT cells on the survival rate in patients with all studied tumors with overall effect of a pooled hazard ratio of 0.89 (95% CI 0.81 to 0.98; p = 0.01). A highly statistical heterogeneity was noted between studied tumor with I2 = 87%; p = 0.00001. CONCLUSIONS: Taken together, this study would present a new insight into the impact of iNKT cells correlate with caner patients’ survival rate and how such cells would be used as a therapeutic target in these patients. Show more

Keywords: Cancer, iNKT cells, Immunotherapy, overall survival, disease free survival

DOI: 10.3233/CBM-240069

Citation: Cancer Biomarkers, vol. 41, no. 2, pp. 155-164, 2024

Authors: Sun, Fengyi | Zhao, Tiantian

Article Type: Research Article

Abstract: BACKGROUND: Cervical cancer is a prevalent malignancy that significantly contributes to morbidity and mortality rates among women in developing nations. Although the association of KIF18A with various cancers has been established, its role in cervical squamous cell carcinoma (CESC) remains elusive. METHODS: The KIF18A impact on the progression of CESC and its underlying mechanism were investigated through comprehensive bioinformatics analysis utilizing publicly available datasets. The levels of KIF18A and CENPE were assessed in clinical CESC samples through western blotting and qRT-PCR. To discover the role and molecular pathways of KIF18A in CESC, a combination of experimental …approaches, including wound-healing, flow cytometry, CCK-8, and Transwell assay, were employed. RESULTS: Our results demonstrate a significant KIF18A expression upregulation in CESC tissues in contrast to healthy tissues. In vitro, KIF18A upregulation was found to enhance cell growth, migration, and invasion and activate the PI3K/AKT signaling pathway while concurrently suppressing apoptosis. Conversely, downregulating KIF18A exhibited contrasting effects. Mechanistically, we observed a positive significant connection between KIF18A and CENPE in CESC cells. CONCLUSION: KIF18A promotes tumor growth in CESC by modulating the PI3K/AKT signaling pathway through regulation of CENPE, making it a potential biomarker for diagnosis and prognosis as well as a therapeutic target. Show more

Keywords: KIF18A, CENPE, Cervical squamous cell carcinoma, PI3K/AKT pathway

DOI: 10.3233/CBM-240074

Citation: Cancer Biomarkers, vol. 41, no. 2, pp. 165-178, 2024