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Concentrating on molecular biomarkers in cancer research, Cancer Biomarkers publishes original research findings (and reviews solicited by the editor) on the subject of the identification of markers associated with the disease processes whether or not they are an integral part of the pathological lesion.
The disease markers may include, but are not limited to, genomic, epigenomic, proteomics, cellular and morphologic, and genetic factors predisposing to the disease or indicating the occurrence of the disease. Manuscripts on these factors or biomarkers, either in altered forms, abnormal concentrations or with abnormal tissue distribution leading to disease causation will be accepted.
Authors: Li, Qi | Zhao, Min | Hu, Dan-Dan | Qin, Jun-Jiao | He, Wei
Article Type: Research Article
Abstract: BACKGROUND: Circular RNAs (circRNAs) are critical regulators of lung adenocarcinoma (LA) progression. Although a molecular marker targeting hsa_circ_0000018 has been developed and used for diagnosing colon cancer, the role of this circRNA in LA progression has not been explored till now. OBJECTIVES: This study aimed to elucidate the role and regulatory mechanisms of hsa_circ_0000018 in LA progression. METHODS: LA tissues and corresponding adjacent non-tumor tissues were collected from 36 patients to confirm the levels of circRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). We also cultured two …LA cell lines (A549, PC-9), and the human normal lung epithelial cell line BEAS-2B. Cell function experiments were conducted to assess malignancy in LA cells, including proliferation, migration, and invasion, following forced hsa_circ_0000018 expression. The correlation between hsa_circ_0000018, let-7f-5p, and family with sequence similarity 96 member A (FAM96A) was confirmed by using starBase (miRNA-circRNA interaction database), luciferase assay, and western blotting. RESULTS: Expression of hsa_circ_0000018 and FAM96A was reduced, whereas that of let-7f-5p was upregulated in LA. Cell function assays revealed that upregulation of hsa_circ_0000018 had a suppressive effect on the proliferation, migration, and invasion of LA cells. Additionally, hsa_circ_0000018 sponge binds let-7f-5p, resulting in upregulation of FAM96A expression. CONCLUSION: Our data reveal hsa_circ_0000018 as a tumor suppressor in LA that targets the let-7f-5p/FAM96A axis. Our findings enrich the known regulatory network of circRNAs in LA. Show more
Keywords: hsa_circ_0000018, lung adenocarcinoma, let-7f-5p, FAM96A, circRNAs
DOI: 10.3233/CBM-230111
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-9, 2023
Authors: Singh, Varsha | Katiyar, Amit | Malik, Prabhat | Kumar, Sunil | Mohan, Anant | Singh, Harpreet | Jain, Deepali
Article Type: Research Article
Abstract: OBJECTIVES: Significant progress has been made in the treatment of patients with pulmonary adenocarcinoma (ADCA) based on molecular profiling. However, no such molecular target exists for squamous cell carcinoma (SQCC). An exome sequence may provide new markers for personalized medicine for lung cancer patients of all subtypes. The current study aims to discover new genetic markers that can be used as universal biomarkers for non-small cell lung cancer (NSCLC). METHODS: WES of 19 advanced NSCLC patients (10 ADCA and 9 SQCC) was performed using Illumina HiSeq 2000. Variant calling was performed using GATK HaplotypeCaller and then …the impacts of variants on protein structure or function were predicted using SnpEff and ANNOVAR. The clinical impact of somatic variants in cancer was assessed using cancer archives. Somatic variants were further prioritized using a knowledge-driven variant interpretation approach. Sanger sequencing was used to validate functionally important variants. RESULTS: We identified 24 rare single-nucleotide variants (SNVs) including 17 non-synonymous SNVs, and 7 INDELs in 18 genes possibly linked to lung carcinoma. Variants were classified as known somatic (n = 10), deleterious (n = 8), and variant of uncertain significance (n = 6). We found TBP and MPRIP genes exclusively associated with ADCA subtypes, FBOX6 with SQCC subtypes and GPRIN2, KCNJ18 and TEKT4 genes mutated in all the patients. The Sanger sequencing of 10 high-confidence somatic SNVs showed 100% concordance in 7 genes, and 80% concordance in the remaining 3 genes. CONCLUSIONS: Our bioinformatics analysis identified KCNJ18, GPRIN2, TEKT4, HRNR, FOLR3, ESSRA, CTBP2, MPRIP, TBP, and FBXO6 may contribute to progression in NSCLC and could be used as new biomarkers for the treatment. The mechanism by which GPRIN2, KCNJ12, and TEKT4 contribute to tumorigenesis is unclear, but our results suggest they may play an important role in NSCLC and it is worth investigating in future. Show more
Keywords: Non-small cell lung cancer, adenocarcinoma, squamous cell carcinoma, biomarker, whole-exome sequencing
DOI: 10.3233/CBM-220211
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-18, 2023
Authors: Aluksanasuwan, Siripat | Somsuan, Keerakarn | Ngoenkam, Jatuporn | Chutipongtanate, Somchai | Pongcharoen, Sutatip
Article Type: Research Article
Abstract: BACKGROUND: Lung adenocarcinoma (LUAD) is a major histological subtype of lung cancer with a high mortality rate worldwide. Heat shock protein family D member 1 (HSPD1, also known as HSP60) is reported to be increased in tumor tissues of lung cancer patients compared with healthy control tissues. OBJECTIVE: We aimed to investigate the roles of HSPD1 in prognosis, carcinogenesis, and immune infiltration in LUAD using an integrative bioinformatic analysis. METHODS: HSPD1 expression in LUAD was investigated in several transcriptome-based and protein databases. Survival analysis was performed using the KM plotter and OSluca databases, …while prognostic significance was independently confirmed through univariate and multivariate analyses. Integrative gene interaction network and enrichment analyses of HSPD1-correlated genes were performed to investigate the roles of HSPD1 in LUAD carcinogenesis. TIMER and TISIDB were used to analyze correlation between HSPD1 expression and immune cell infiltration. RESULTS: The mRNA and protein expressions of HSPD1 were higher in LUAD compared with normal tissues. High HSPD1 expression was associated with male gender and LUAD with advanced stages. High HSPD1 expression was an independent prognostic factor associated with poor survival in LUAD patients. HSPD1-correlated genes with prognostic impact were mainly involved in aberrant ribosome biogenesis, while LUAD patients with high HSPD1 expression had low tumor infiltrations of activated and immature B cells and CD4+ T cells. CONCLUSIONS: HSPD1 may play a role in the regulation of ribosome biogenesis and B cell-mediated immunity in LUAD. It could serve as a predictive biomarker for prognosis and immunotherapy response in LUAD. Show more
Keywords: Lung adenocarcinoma, HSPD1, ribosome biogenesis, immune infiltration, biomarker, prognosis
DOI: 10.3233/CBM-220442
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-16, 2023
Authors: Zhu, Ziwen | Jiang, Weizhen | Zhou, Danhong | Zhu, Weidong | Chen, Cheng
Article Type: Research Article
Abstract: BACKGROUND: In clinical practice, preoperative identification of mixed ground-glass opacity (mGGO) nodules with micropapillary component (MPC) to facilitate the implementation of individualized therapeutic strategies and avoid unnecessary surgery is increasingly important OBJECTIVE: This study aimed to build a predictive model based on clinical and radiological variables for the early identification of MPC in lung adenocarcinoma presenting as mGGO nodules. METHODS: The enrolled 741 lung adenocarcinoma patients were randomly divided into a training cohort and a validation cohort (3:1 ratio). The pathological specimens and preoperative images of malignant mGGO nodules from the study subjects …were retrospectively reviewed. Furthermore, in the training cohort, selected clinical and radiological variables were utilized to construct a predictive model for MPC prediction. RESULTS: The MPC was found in 228 (43.3%) patients in the training cohort and 72 (41.1%) patients in the validation cohort. Based on the predictive nomogram, the air bronchogram was defined as the most dominant independent risk factor for MPC of mGGO nodules, followed by the maximum computed tomography (CT) value (> 200), adjacent to pleura, gender (male), and vacuolar sign. The nomogram demonstrated good discriminative ability with a C-index of 0.783 (95%[CI] 0.744–0.822) in the training cohort and a C-index of 0.799 (95%[CI] 0.732–0.866) in the validation cohort Additionally, by using the bootstrapping method, this predictive model calculated a corrected AUC of 0.774 (95% CI: 0.770–0.779) in the training cohort. CONCLUSIONS: This study proposed a predictive model for preoperative identification of MPC in known lung adenocarcinomas presenting as mGGO nodules to facilitate individualized therapy. This nomogram model needs to be further externally validated by subsequent multicenter studies. Show more
Keywords: Mixed ground-glass opacity (mGGO), micropapillary component (MPC), lung adenocarcinoma, predictive model, nomogram
DOI: 10.3233/CBM-230104
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-11, 2023
Authors: Chen, Cheng | Wang, Caiming | Liu, Wei | Chen, Jiacheng | Chen, Liang | Luo, Xiangxiang | Wu, Jincai
Article Type: Research Article
Abstract: BACKGROUND: Cms1 ribosomal small subunit homolog (CMSS1) is an RNA-binding protein that may play an important role in tumorigenesis and development. OBJECTIVE: RNA-seq data from the GEPIA database and the UALCAN database were used to analyze the expression of CMSS1 in liver hepatocellular carcinoma (LIHC) and its relationship with the clinicopathological features of the patients. METHODS: LinkedOmics was used to identify genes associated with CMSS1 expression and to identify miRNAs and transcription factors significantly associated with CMSS1 by GSEA. RESULTS: The expression level of CMSS1 in hepatocellular carcinoma tissues was …significantly higher than that in normal tissues. In addition, the expression level of CMSS1 in advanced tumors was significantly higher than that in early tumors. The expression level of CMSS1 was higher in TP53-mutated tumors than in non-TP53-mutated tumors. CMSS1 expression levels were strongly correlated with disease-free survival (DFS) and overall survival (OS) in patients with LIHC, and high CMSS1 expression predicted poorer OS (P < 0.01) and DFS (P < 0.01). Meanwhile, our results suggested that CMSS1 is associated with the composition of the immune microenvironment of LIHC. CONCLUSIONS: The present study suggests that CMSS1 is a potential molecular marker for the diagnosis and prognostic of LIHC. Show more
Keywords: CMSS1, hepatocellular carcinoma, . bioinformatics, diagnosis, prognosis
DOI: 10.3233/CBM-230209
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-10, 2023
Authors: Heredia, David | Bolaño-Guerra, Laura | Valencia-Velarde, Angel | Santoyo, Edgar Varela | Lara-Mejía, Luis | Cárdenas-Fernández, Daniela | Orozco, Mario | Cruz-Rico, Graciela | Arrieta, Oscar
Article Type: Research Article
Abstract: BACKGROUND: Liquid biopsy (LB) is used to detect epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) and has been demonstrated to have prognostic and predictive value. OBJECTIVE: To associate the rates of EGFR and T790M mutations detected by LB during disease progression after first- or second-generation EGFR-TKIs with clinical characteristics and survival outcomes. METHODS: From January 2018 to December 2021, 295 patients with advanced EGFR mutant (EGFRm) NSCLC treated with first- or second-generation EGFR-TKIs were retrospectively analyzed. LB was collected at the time of progression. The frequency of …EGFR T790M mutations, overall survival (OS), and the clinical characteristics associated with LB positivity were determined. RESULTS: The prevalence of EGFR T790M mutation detected using LB was 44%. In patients with negative vs. positive LB, the median OS was 45.0 months vs. 25.0 months (p = 0.0001), respectively. Patients with a T790M mutation receiving osimertinib had a median OS of 44 months (95% CI [33.05–54.99]). Clinical characteristics associated with positive LB at progression extra-thoracic involvement, > 3 metastatic sites, and bone metastases. CONCLUSIONS: Our findings showed that LB positivity was associated with worse survival outcomes and specific clinical characteristics. This study also confirmed the feasibility and detection rate of T790M mutation in a Latin American population. Show more
Keywords: EGFRm NSCLC, liquid biopsy, T790M mutation, osimertinib, ctDNA
DOI: 10.3233/CBM-230124
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-11, 2023
Authors: Karamti, Hanen | Alharthi, Raed | Umer, Muhammad | Shaiba, Hadil | Ishaq, Abid | Abuzinadah, Nihal | Alsubai, Shtwai | Ashraf, Imran
Article Type: Research Article
Abstract: Breast cancer is a major cause of female deaths, especially in underdeveloped countries. It can be treated if diagnosed early and chances of survival are high if treated appropriately and timely. For timely and accurate automated diagnosis, machine learning approaches tend to show better results than traditional methods, however, accuracy lacks the desired level. This study proposes the use of an ensemble model to provide accurate detection of breast cancer. The proposed model uses the random forest and support vector classifier along with automatic feature extraction using an optimized convolutional neural network (CNN). Extensive experiments are performed using the original, …as well as, CNN-based features to analyze the performance of the deployed models. Experimental results involving the use of the Wisconsin dataset reveal that CNN-based features provide better results than the original features. It is observed that the proposed model achieves an accuracy of 99.99% for breast cancer detection. Performance comparison with existing state-of-the-art models is also carried out showing the superior performance of the proposed model. Show more
Keywords: Breast cancer detection, image processing, healthcare, machine learning, ensemble learning, deep convoluted features
DOI: 10.3233/CBM-230294
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-16, 2023
Authors: Yao, Ningning | Hou, Qing | Liang, Yu | Cao, Xin | Sun, Bochen | Wei, Lijuan | Sun, Ruifang | Cao, Jianzhong
Article Type: Research Article
Abstract: BACKGROUND: Aspartate aminotransferase (AST), an indicator of liver cell damage, was related to the prognosis of certain malignant tumors. OBJECTIVE: This study examined the predictive value of AST in patients with extranodal natural killer/T cell lymphoma (ENKTL). METHODS: We reviewed 183 cases diagnosed with ENKTL and selected 26 U/L as the optimum cut-off value of AST. We used the univariate and multivariate Cox regression to compare the different AST groups’ overall survival (OS) and progression-free survival (PFS). RESULTS: Prior to propensity score matching (PSM), Kaplan-Meier analysis showed that patients in …the low AST subgroup had better OS and PFS than the high AST subgroup. Multivariate analysis revealed that AST was an independent indicator for prognosis. After PSM, the low AST subgroup maintained a significantly better OS and PFS than the high AST subgroup. CONCLUSION: AST might represent a significant prognostic marker for ENKTL patients. Show more
Keywords: Serum aspartate aminotransferase, extranodal natural killer/T cell lymphoma, nasal type, survival, prognosis
DOI: 10.3233/CBM-230068
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-11, 2023
Authors: Attia, Amany Selim | Hussein, Samia | Sameh, Hend | Khalil, Amr | Waley, Ahmad Barakat | Matar, Ihab | Sameh, Reham
Article Type: Research Article
Abstract: BACKGROUND: Papillary thyroid carcinoma (PTC) is the most frequent thyroid malignancy. Histopathological examination is widely accepted as the gold standard test for the diagnosis of PTC. However, the histopathological examination sometimes can’t differentiate PTC from other thyroid diseases. Differentiating PTC from other thyroid diseases is essential for a therapeutic approach and prognosis. OBJECTIVES: The current study was performed to investigate the utility of TROP-2, SPL-2, and CXCL12 mRNA and protein expression in discriminating PTC from other thyroid diseases that mimic PTC. METHODS: The current study was performed on 75 cases of surgically resected …thyroid glands. The cases were distributed in two groups: the PTC group and the non-PTC group. The PTC group consisted of 35 cases (25 patients of the classic PTC variant and 10 patients of the PTC follicular variant). The non-PTC group consisted of 40 cases (10 cases were multinodular goiter, 5 cases were Graves’ disease, 5 cases were Hashimoto thyroiditis, 15 patients were follicular adenoma (FA) and 5 cases were follicular carcinoma). TROP-2 , SPL-2 , and CXCL12 mRNA expression were estimated by qRT-PCR, and protein expression was estimated by immunohistochemistry. RESULTS: There were upregulated TROP-2, SPL-2, and CXCL12 mRNA and protein expressions in PTC compared to non-PTC (P < 0.001, for each). There was a statistically significant upregulation in the mRNA expression of the three genes among PTC cases with larger tumor sizes (P < 0.001, for each), those with tumor stages III and IV (P = 0.008, 0.002 and < 0.001 respectively), and those with LN metastasis (P < 0.001, for each). Moreover, there was a statistically significant upregulation in CXCL-12 gene expression among PTC cases with extra-thyroid extension (P < 0.001). CONCLUSION: mRNA expression of TROP-2, SPL-2, and CXCL12 among PTC cases increased in larger tumor size, tumor stages III and IV, and LN metastasis. Moreover, there was an increase in CXCL-12 gene expression among PTC cases with extra-thyroid extension. Thus, TROP-2, SPL-2, and CXCL12 expressions could be possible diagnostic and prognostic markers in PTC. Show more
Keywords: TROP-2, SPL-2, CXCL12, papillary thyroid carcinoma
DOI: 10.3233/CBM-230230
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-11, 2023
Authors: Zhang, Yuke | Liu, Kai | Wang, Jianzhong
Article Type: Research Article
Abstract: BACKGROUND: Osteosarcoma (OS) is a relatively rare malignant bone tumor in teenagers; however, its molecular mechanisms are not yet understood comprehensively. OBJECTIVE: The study aimed to use necroptosis-related genes (NRGs) and their relationships with immune-related genes to construct a prognostic signature for OS. METHODS: TARGET-OS was used as the training dataset, and GSE 16091 and GSE 21257 were used as the validation datasets. Univariate regression, survival analysis, and Kaplan-Meier curves were used to screen for hub genes. The immune-related targets were screened using immune infiltration assays and immune checkpoints. The results were validated …using nomogram and decision curve analyses (DCA). RESULTS: Using univariate Cox regression analysis, TNFRSF1A was screened from 14 NRGs as an OS prognostic signature. Functional enrichment was analyzed based on the median expression of TNFRSF1A. The prognosis of the TNFRSF1A low-expression group in the Kaplan-Meier curve was notably worse. Immunohistochemistry analysis showed that the number of activated T cells and tumor purity increased considerably. Furthermore, the immune checkpoint lymphocyte activation gene 3 (LAG-3) is a possible target for intervention. The nomogram accurately predicted 1-, 3-, and 5-year survival rates. DCA validated the model (C = 0.669). Conclusion: TNFRSF1A can be used to elucidate the potential relationship between the immune microenvironment and NRGs in OS pathogenesis. Show more
Keywords: Osteosarcoma, necroptosis, tumor immune microenvironment, TNFRSF1A, prognosis
DOI: 10.3233/CBM-230086
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-14, 2023
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