Cancer Biomarkers - Volume 36, issue 3

Authors: Bielak, Cezary | Arya, Arvind | Savill, Stuart

Article Type: Review Article

Abstract: Half of all people aged 50 and over develop a thyroid nodule in their lifetime, exclusion of cancer is required in each case. Nodule tissue sampling is performed by way of fine needle aspiration biopsy (FNAB), however a definite diagnosis is possible only in 30% of cases. The discovery of a diagnostic biomarker to discriminate between thyroid cancer and benign nodules would therefore greatly improve current clinical practice. Using the databases of Medline, Embase and Pubmed we identified 21 original research papers examining various microRNA as potential biomarkers. Currently, the most evidence supporting diagnostic utility exists for miRNA-222. It has …been shown repeatedly to have potential in diagnosis of PTC & MTC as well as being linked with the most prognostic factors of all microRNA. To a lesser extent, evidence seems to support the diagnostic and prognostic utility of miR-146b, Let-7 family, miR-221 for PTC and miR-21 for PTC & FTC. MicroRNA appear to show promise as potential diagnostic and prognostic biomarkers, however there is still not enough data to produce a consensus. Continued research should be undertaken with streamlined protocols. Show more

Keywords: MicroRNA, biomarker, serum, thyroid, cancer

DOI: 10.3233/CBM-210504

Citation: Cancer Biomarkers, vol. 36, no. 3, pp. 193-205, 2023

Authors: Masood, Atika | Sarfaraz, Rahat | Zaki, Saima | Shami, Amira | Khaliq, Saba | Naseem, Nadia

Article Type: Research Article

Abstract: BACKGROUND: Genetic mutations, peritoneal metastasis and frequent development of chemoresistance worsen the prognosis of ovarian carcinoma. OBJECTIVE: The objective of the study is to determine mutations in cancer susceptibility genes in relation with chemotherapy response. METHODS: In this follow up descriptive study, 47 consenting female patients diagnosed with surface epithelial ovarian cancer were observed for six months after completion of chemotherapy to see the treatment response. For genetic analysis, the DNA extraction was done and the genomic regions of different exons of BRCA1/2, PALB2, CHEK2, BAP1, CTNNB1, HOXB13, and PIK3CA were amplified using …gene specific primers followed by Sanger Sequencing. RESULTS: 86.7% of the patients were sensitive to chemotherapy whereas 13.3% showed resistance. Genetic variants of BRCA1 in 7%, BRCA2 in 4.7%, PIK3CA in 9.3%, PALB2 in 7%, CHEK2 in 2.3%, BAP1 in 2.3%, and CTNNB1 in 2.3% of the patients were found. There was also a significant association between TNM stage and the treatment response (p < 0.01). Of the patients with no mutations, 90.9% showed chemosensitivity as opposed to 70% in mutations group. CONCLUSION: Our study exhibits the pivotal role of genetic analysis in predicting the treatment response and paving pathway for patient tailored targeted therapy in Pakistani population. Show more

Keywords: Epithelial ovarian cancer, BRCA1/2, somatic mutations, chemotherapy, prognosis

DOI: 10.3233/CBM-220267

Citation: Cancer Biomarkers, vol. 36, no. 3, pp. 207-219, 2023

Authors: He, Xue | Hu, Jing | Yan, Changjian | Liu, Xiaoni | Zhao, Yali | Yang, Ping | Wang, Jing | Li, Shaoxiang | Zhang, Wei | Dong, Gehong | Zhang, Weilong | Jing, Hongmei

Article Type: Research Article

Abstract: BACKGROUND: Nearly half of adult acute myeloid leukemia (AML) patients were classified into cytogenetic normal acute myeloid leukemia (CN-AML). The expression level of Trophinin associated protein (TROAP) was proven to be associated with the prognosis of several cancers, but it is still unclear in the prognosis of patients with CN-AML. METHODS: We integrated CN-AML patient samples from 4 datasets to analyze the relationship between TROAP expression and the survival of CN-AML. In addition, we investigated 92 AML patients of The Cancer Genome Atlas (TCGA) database to analyze the relationship between TROAP expression and the survival of …AML patients received chemotherapy. We investigated the relationship between the expression of TROAP and drug sensitivity in AML cell lines. RESULTS: CN-AML patients with high TROAP expression were related to good event-free survival (EFS) and overall survival (OS). In AML patients received chemotherapy, high TROAP expression was associated with good survival prognosis. Additionally, the expression of TROAP gene in leukemia stem cells (LSC) + group was lower. Among multiple drugs, the lower the expression of TROAP, the lower the IC50. CONCLUSION: TROAP could serve as an independent predictor of CN-AML patients and could act as a potential biomarker for the prognosis of CN-AML. TROAP expression levels were closely correlated with the drug sensitivity of multiple drugs. Show more

Keywords: TROAP, acute myeloid leukemia, cytogenetic type, prognosis

DOI: 10.3233/CBM-210042

Citation: Cancer Biomarkers, vol. 36, no. 3, pp. 221-230, 2023

Authors: Yin, Zi | Ma, Tingting | Chen, Sheng | Yu, Min

Article Type: Research Article

Abstract: BACKGROUD: Hepatocellular carcinoma (HCC) is characterized by occult onset, rapid progression and poor prognosis. CXC chemokines play an important role in tumor microenvironment and development. OBJECTIVE: The potential mechanistic values of CXC chemokines as clinical biomarkers and therapeutic targets in HCC have not been fully clarified. METHODS: ONCOMINE, UALCAN, GEPIA, cBioPortal, SurvExpress, MethSurv, SurvivalMeth, String, GeneMANIA, DAVID, Metascape, TRRUST, LinkedOmics, and Timer were applied in this study. RESULTS: The transcriptional levels of CXCL9/16/17 in HCC tissues were significantly elevated while CXCL1/2/5/6/7/12/14 were significantly reduced. Significant correlation was found between the expression …of CXC3/5 and the pathological stage of HCC patients. High level of CXCL4 was associated with a longer disease-free survival. For overall survival, lower expressions of CXCL1/3/5/8 and higher expressions of CXCL2 were associated with a better outcome. In addition, the prognostic values of CXC chemokines signature in HCC were explored in four independent cohorts, the high-risk group displayed unfavorable survival outcome compared with the low-risk group. And for the prognostic value of the DNA methylation of CXC chemokines, we identified the CpGs which were significantly associated with prognosis in HCC patients. DNA methylation signature analysis also showed a statistically significant association between the high- and low-risk groups. For potential mechanism, the neighbor gene networks, interaction analyses, functional enrichment analyses of CC chemokine receptors in HCC were performed, the transcription factor targets, kinase targets, and miRNA targets of CXC chemokines were also identified in HCC. We also found significant correlations among CXC chemokines expression and the infiltration of immune cells, the tumor infiltration levels among HCC with different somatic copy number alterations of these chemokine receptors were also assessed. Moreover, the Cox proportional hazard model showed that CCR2/6/8/12, B cell, macrophage and dendritic cell were significantly related to the clinical outcome of HCC patients. CONCLUSION: CXC chemokines might serve as therapeutic targets and prognostic biomarkers in HCC. Show more

Keywords: CXC chemokines, HCC, prognostic biomarker, therapeutic target

DOI: 10.3233/CBM-210300

Citation: Cancer Biomarkers, vol. 36, no. 3, pp. 231-250, 2023

Authors: Lin, Chih-Lang | Chien, Rong-Nan | Chen, Li-Wei | Chu, Yu-De | Yeh, Chau-Ting

Article Type: Research Article

Abstract: BACKGROUND: Sorafenib and lenvatinib are tyrosine kinase inhibitors widely used in the targeted therapy to treat advanced hepatocellular carcinoma (aHCC). The GALNT14 -rs9679162 genotype is a predictor of therapeutic outcome in multiple gastrointestinal cancers. OBJECTIVE: To investigate the predictive role of the GALNT14 -rs9679162 genotype in aHCC treated with sorafenib or lenvatinib. METHODS: Totally 350 real-world patients with aHCC received sorafenib or lenvatinib were enrolled for GALNT14 -rs9679162 genotyping and outcome analysis. Kaplan-Meier and Cox regression analysis were conducted to evaluate therapeutic outcomes. Cell-based assays were performed to determine the underlying mechanism. …RESULTS: Kaplan-Meier and Cox regression analysis showed that the “GG” genotype was not associated with overall survival (OS) when all patients were included. However, it was associated with shorter OS in specific clinical subgroups, including anti-hepatitis C virus antibody-positive (n = 108; P = 0.005) and hepatitis B surface antigen-negative (n = 117; P = 0.002) patients. Intriguingly, hepatitis B virus X protein trans-suppressed the GALNT14 promoter, thereby reducing the elevated expression of GALNT14 in hepatoma cells, which partially contributed to the inability of the GALNT14 -rs9679162 genotypes to predict the outcome of hepatitis B-related HCC. Finally, by analyzing the outcomes of 52 patients with aHCC treated with lenvatinib, patients with the “GG” genotype were associated with a favorable/shorter time-to-response (P = 0.013). CONCLUSIONS: The GALNT14 -rs9679162 “GG” genotype predicted shorter OS in patients with HBsAg-negative aHCC treated with sorafenib, but predicted a favorable response in all patients with aHCC treated with lenvatinib. Show more

Keywords: Single nucleotide polymorphism, Rs9679162 genotype, advanced hepatocellular carcinoma (HCC), genetic biomarker and overall survival

DOI: 10.3233/CBM-220042

Citation: Cancer Biomarkers, vol. 36, no. 3, pp. 251-266, 2023