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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: Dang, Tianfeng | Yu, Jieqing | Yu, Yanqing | Jiang, Junjie | Shi, Yang | Yu, Simin | Peng, Congli | Min, Xiang | Xiong, Yuanping | Long, Ping | Zhou, Wensheng | Dai, Daofeng
Article Type: Research Article
Abstract: GPX4 has attracted much attention as a key molecule of cell ferroptosis, but its role in cell apoptosis is rarely reported, and its role in apoptosis of thyroid cancer (TC) cell has not been reported. The analysis of TCGA database showed that both GPX4 and FKBP8 were highly expressed in TC tumor tissues; The expression of GPX4 and FKBP8 were positively correlated. The immunohistochemical analysis further confirmed that GPX4 and FKBP8 were highly expressed in TC tumor tissues. In addition, the high expression of GPX4 and FKBP8 were both significantly correlated with the poor prognosis of TC. Silencing GPX4 significantly …inhibited the proliferation, induced apoptosis of TC cells, and reduced tumor growth in mice. The co-immunoprecipitation assay revealed a physical interaction between GPX4 and FKBP8 observed in the TC cells. Knockdown of FKBP8 significantly inhibited the proliferation and induced apoptosis of TC cells. Rescue experiments suggested that knockdown of FKBP8 could reverse the strengthens of cell proliferation and apoptosis and the higher expression of FKBP8 and Bcl-2 caused by overexpression of GPX4. Our results suggest that the GPX4/FKBP8/Bcl-2 axis promotes TC development by inhibiting TC cell apoptosis, which provides potential molecular targets for TC therapeutic strategies. Show more
Keywords: Apoptosis, cell proliferation, molecular targets, programmed cell death, thyroid cancer
DOI: 10.3233/CBM-230220
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-12, 2023
Authors: Záveský, Luděk | Jandáková, Eva | Weinberger, Vít | Minář, Luboš | Kohoutová, Milada | Slanař, Ondřej
Article Type: Research Article
Abstract: BACKGROUND: Breast cancer is the most commonly occurring cancer worldwide and is the main cause of death from cancer in women. Novel biomarkers are highly warranted for this disease. OBJECTIVE: Evaluation of novel long non-coding RNAs biomarkers for breast cancer. METHODS: The study comprised the analysis of the expression of 71 candidate lncRNAs via screening, six of which (four underexpressed, two overexpressed) were validated and analyzed by qPCR in tumor tissues associated with NST breast carcinomas, compared with the benign samples and with respect to their clinicopathological characteristics. RESULTS: The …results indicated the tumor suppressor roles of PTENP1, GNG12-AS1, MEG3 and MAGI2-AS3. Low levels of both PTENP1 and GNG12-AS1 were associated with worsened progression-free and overall survival rates. The reduced expression of GNG12-AS1 was linked to the advanced stage. A higher grade was associated with the lower expression of PTENP1, GNG12-AS1 and MAGI2-AS3. Reduced levels of both MEG3 and PTENP1 were linked to Ki-67 positivity. The NRSN2-AS1 and UCA1 lncRNAs were overexpressed; higher levels of UCA1 were associated with multifocality. CONCLUSIONS: The results suggest that the investigated lncRNAs may play important roles in breast cancer and comprise a potential factor that should be further evaluated in clinical studies. Show more
Keywords: Breast cancer, GNG12-AS1, clinical outcomes, long non-coding RNAs, MAGI2-AS3, MEG3, NRSN2-AS1, PTENP1, UCA1
DOI: 10.3233/CBM-230259
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-18, 2024
Authors: Paez, Rafael | Rowe, Dianna J. | Deppen, Stephen A. | Grogan, Eric L. | Kaizer, Alexander | Bornhop, Darryl J. | Kussrow, Amanda K. | Barón, Anna E. | Maldonado, Fabien | Kammer, Michael N.
Article Type: Research Article
Abstract: BACKGROUND: Assessing the clinical utility of biomarkers is a critical step before clinical implementation. The reclassification of patients across clinically relevant subgroups is considered one of the best methods to estimate clinical utility. However, there are important limitations with this methodology. We recently proposed the intervention probability curve (IPC) which models the likelihood that a provider will choose an intervention as a continuous function of the probability, or risk, of disease. OBJECTIVE: To assess the potential impact of a new biomarker for lung cancer using the IPC. METHODS: The IPC derived from the …National Lung Screening Trial was used to assess the potential clinical utility of a biomarker for suspected lung cancer. The summary statistics of the change in likelihood of intervention over the population can be interpreted as the expected clinical impact of the added biomarker. RESULTS: The IPC analysis of the novel biomarker estimated that 8% of the benign nodules could avoid an invasive procedure while the cancer nodules would largely remain unchanged (0.1%). We showed the benefits of this approach compared to traditional reclassification methods based on thresholds. CONCLUSIONS: The IPC methodology can be a valuable tool for assessing biomarkers prior to clinical implementation. Show more
Keywords: Biomarkers, clinical utility, Intervention Probability Curve, indeterminate pulmonary nodule, net reclassification index
DOI: 10.3233/CBM-230054
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-8, 2023
Authors: Li, Thomas Z. | Xu, Kaiwen | Chada, Neil C. | Chen, Heidi | Knight, Michael | Antic, Sanja | Sandler, Kim L. | Maldonado, Fabien | Landman, Bennett A. | Lasko, Thomas A.
Article Type: Research Article
Abstract: BACKGROUND: Large community cohorts are useful for lung cancer research, allowing for the analysis of risk factors and development of predictive models. OBJECTIVE: A robust methodology for (1) identifying lung cancer and pulmonary nodules diagnoses as well as (2) associating multimodal longitudinal data with these events from electronic health record (EHRs) is needed to optimally curate cohorts at scale. METHODS: In this study, we leveraged (1) SNOMED concepts to develop ICD-based decision rules for building a cohort that captured lung cancer and pulmonary nodules and (2) clinical knowledge to define time windows for …collecting longitudinal imaging and clinical concepts. We curated three cohorts with clinical data and repeated imaging for subjects with pulmonary nodules from our Vanderbilt University Medical Center. RESULTS: Our approach achieved an estimated sensitivity 0.930 (95% CI: [0.879, 0.969]), specificity of 0.996 (95% CI: [0.989, 1.00]), positive predictive value of 0.979 (95% CI: [0.959, 1.000]), and negative predictive value of 0.987 (95% CI: [0.976, 0.994]) for distinguishing lung cancer from subjects with SPNs. CONCLUSION: This work represents a general strategy for high-throughput curation of multi-modal longitudinal cohorts at risk for lung cancer from routinely collected EHRs. Show more
Keywords: Pulmonary nodules, lung cancer, EHR mining, multimodal longitudinal cohorts
DOI: 10.3233/CBM-230340
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-9, 2024
Authors: Xie, Kai | Wang, Bin | Pang, Pei | Li, Guangbin | Yang, Qianqian | Fang, Chen | Jiang, Wei | Feng, Yu | Ma, Haitao
Article Type: Research Article
Abstract: BACKGROUND: Lung adenocarcinoma (LUAD) is a prevalent form of malignancy globally. Disulfidptosis is novel programmed cell death pathway based on disulfide proteins, may have a positive impact on the development of LUAD treatment strategies. OBJECTIVE: To investigate the impact of disulfidptosis-related genes (DRGs) on the prognosis of LUAD, developed a risk model to facilitate the diagnosis and prognostication of patients. We also explored ACTN4 (DRGs) as a new therapeutic biomarker for LUAD. METHODS: We investigated the expression patterns of DRGs in both LUAD and noncancerous tissues. To assess the prognostic value of …the DRGs, we developed risk models through univariate Cox analysis and lasso regression. The expression and function of ACTN4 was evaluated by qRT-PCR, immunohistochemistry and in vitro experiments. The TIMER examined the association between ACTN4 expression and immune infiltration in LUAD. RESULTS: Ten differentially expressed DRGs were identified. And ACTN4 was identified as potential risk factors through univariate Cox regression analysis (P < 0.05). ACTN4 expression and riskscore were used to construct a risk model to predict overall survival in LUAD, and high-risk demonstrated a significantly higher mortality rate compared to the low-risk cohort. qRT-PCR and immunohistochemistry assays indicated ACTN4 was upregulated in LUAD, and the upregulation was associated with clinicopathologic features. In vitro experiments showed the knockdown of ACTN4 expression inhibited the proliferation in LUAD cells. The TIMER analysis demonstrated a correlation between the expression of ACTN4 and the infiltration of diverse immune cells. Elevated ACTN4 expression was associated with a reduction in memory B cell count. Additionally, the ACTN4 expression was associated with m6A modification genes. CONCLUSIONS: Our study introduced a prognostic model based on DRGs, which could forecast the prognosis of patients with LUAD. The biomarker ACTN4 exhibits promise for the diagnosis and management of LUAD, given its correlation with tumor immune infiltration and m6A modification. Show more
Keywords: Disulfidptosis, lung adenocarcinoma, ACTN4, immune infiltration, therapeutic target
DOI: 10.3233/CBM-230276
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-14, 2024
Authors: Liu, Yang | Pang, Zhongqi | Wang, Jianshe | Wang, Jinfeng | Ji, Bo | Xu, Yidan | He, Jiaxin | Zhang, Lu | Han, Yansong | Shen, Linkun | Xu, Wanhai | Ren, Minghua
Article Type: Research Article
Abstract: BACKGROUND: N6-methyladenosine (m6A) is the most frequent RNA modification in mammals, and its role in bladder cancer (BC) remains rarely revealed. OBJECTIVE: To predict the value of m6A-related genes in prognosis and immunity in BC. METHODS: We performed multiple omics analysis of 618 TCGA and GEO patients and used principal component analysis (PCA) to calculate the m6A score for BC patients. RESULTS: We described the multiple omics status of 23 m6A methylation-related genes (MRGs), and four m6A clusters were identified, which showed significant differences in immune infiltration and biological pathways. …Next, we intersected the differential genes among m6A clusters, and 11 survival-related genes were identified, which were used to calculate the m6A score for the patients. We found that the high-score (HS) group showed lower tumor mutation burden (TMB) and TP53 mutations and better prognosis than the low-score (LS) group. Lower immune infiltration, higher expression of PD-L1, PD-1, and CTLA4, and higher immune dysfunction and immune exclusion scores were identified in the LS group, suggesting a higher possibility of immune escape. Finally, the experimental verification shows that the m6A related genes, such as IGFBP1, plays an important role in the growth and metastasis of bladder cancer. CONCLUSIONS: These findings revealed the important roles of m6A MRGs in predicting prognosis, TMB status, TP53 mutation, immune functions and immunotherapeutic response in BC. Show more
Keywords: N6-methyladenosine, bladder cancer, prognosis, immunotherapy, m6A score
DOI: 10.3233/CBM-230286
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-16, 2024
Authors: Karataş, Fatih | Acat, Murat | Karatas, Hatice Gulsah | İnci, Fatih | Dikiş, Özlem Sengören
Article Type: Research Article
Abstract: BACKGROUND: Despite Non-small cell lung cancer (NSCLC) ranks among the most deadly cancers worldwide, and currently, apart from a low percentage, targetable molecules have not been identified in its etiopathogenesis. The relationship between the proteoglycans decorin and biglycan, which are present in the extracellular matrix of cells, and transforming growth factor Beta-1 (TGF-B1), has been shown in many cancers. We investigated the significance of these molecules in NSCLC. METHODS: Fasting serum levels of decorin, biglycan, and TGF-B1 were obtained from 48 newly diagnosed NSCLC patients and compared with those of 48 adult control subjects matched for …age and demographics. Demographic data, baseline laboratory values, and ELISA results were compared between the groups. RESULTS: The median age was 65(39–83) similar in both groups. There was no relation between demographic and clinical parameters and the levels of decorin, biglycan, and TGF-B1 in the NSCLC group. However, in comparison to the control group, NSCLC patients had significantly higher levels of biglycan (42.55 ± 27.40 vs. 24.38 ± 12.05 ng/mL, p = 0.026) and TGF-B1 (15.55 ± 9.16 vs. 10.07 ± 7.8 pg/mL, p = 0.001), while decorin levels were significantly lower (6.64 ± 1.92 vs. 10.28 ± 3.13 ng/mL, p = 0.002). In the multivariate regression analysis; Decorin < 8.13 ng/mL (OR, 10.96; 95% CI: 3.440–34.958), current smoking (OR, 3.81; 95% CI: 1.320–10.998), COPD (OR, 43.6; 95% CI: 2.082–913.081), and lower BMI (OR, 1.22; 95% CI: 1.070–1.405, p = 0.003) were identified as independent predictive markers for NSCLC diagnosis. CONCLUSION: The decreased serum decorin level is an independent marker for NSCLC. Further studies are needed to investigate the prognostic significance of decorin on survival and its potential as a target in treatment. Show more
Keywords: Non small cell, lung cancer, decorin, biglycan, TGF-B1
DOI: 10.3233/CBM-230238
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-6, 2023
Authors: Vo, Duc | Liu, Yan | Sood, Anil K. | Rezvani, Katy | Jazaeri, Amir A. | Liu, Jinsong
Article Type: Research Article
Abstract: High grade epithelial ovarian carcinoma is an aggressive tumor. Treatment includes platinum therapy, however it recurs in most patients due to therapy resistance. In this project, we study the immunohistochemical (IHC) expression of five potential biomarkers/prognostic markers in high grade epithelial ovarian carcinoma: EGFR, HLA-G, CD70, c-MET, and NY-ESO1. A cohort of 274 patients is used. We compare the IHC expression with age, stage, ascites status, family history of cancer, disease free survival (DFS) and overall survival (OS). EGFR expression is significantly correlated with family history and worse OS. HLA-G is associated with worse OS. To confirm the results of …EGFR and HLA-G, a second separated cohort of 248 patients is used. Positive EGFR expression again shows worse OS, while HLA-G expression has worse prognostic trend. CD70 has a worse OS trend. C-MET and NY-ESO1 do not have any clinical correlations. EGFR can potentially serve as target in future clinical immune therapy trials. Show more
Keywords: EGFR, HLA-G, CD70, c-MET, NY-ESO1, survival
DOI: 10.3233/CBM-230200
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-10, 2023
Authors: Zhou, Sixu | Wang, Baogui | Wei, Yingying | Dai, Peiru | Chen, Yan | Xiao, Yingyi | Xia, Hongmei | Chen, Chunlin | Yin, Weihua
Article Type: Research Article
Abstract: BACKGROUND: Docetaxel is a yew compound antitumor agent with accurate antitumor efficacy, but its application is limited due to the high and serious adverse effects, and finding effective combination therapy options is a viable strategy. Immune checkpoint inhibitors have become hotspots in enhancing anti-tumor immunity by blocking immune checkpoint signaling pathways, but their response rate to monotherapy use is not high and the efficacy is minimal. OBJECTIVE: To explore the anti-tumor effects and mechanisms of the combination of PD-1 inhibitors and Docetaxel through in vivo experiments and develop a feasible combination treatment for the therapy of …prostate cancer. METHODS: Tumor-bearing mice were subcutaneously injected with 0.1 ml RM-1 cells. Treatment were taken when the tumor growed up to 3 mm, after which the tumor and spleen were removed to test the antitumor effect with Flow cytometric (FACS) analysis, Immunohistochemistry, Western Blot. RESULTS: In this experiment, we found that PD-1 inhibitors combined with Docetaxel had a synergistic effect on mouse prostate cancer, inhibited the growth of prostate cancer, improved survival and reduced adverse reactions, increased spleen and tumor infiltrative CD4 + and CD8 + T cells, especially in group combination with low-dose Docetaxel, and were related to the PI3K/AKT/NFKB-P65/PD-L1 signaling pathway. CONCLUSION: Our study confirms that PD-1 inhibitors in combination with Docetaxel are a viable combination strategy and provide a safe and effective combination option for the clinical treatment of prostate cancer. Show more
Keywords: Prostate cancer, docetaxel, PD-1 inhibitor, camrelizumab, immune checkpoints
DOI: 10.3233/CBM-230090
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-13, 2024
Authors: Yan, Shunkang | Zhang, Jiandong | Li, Lianghe | Chen, Gang | Chen, Zhongsheng | Zhan, Wei
Article Type: Research Article
Abstract: BACKGROUND: Colorectal cancer (CRC) is a common form of cancer, with rectal cancer accounting for approximately one-third of all cases. Among rectal cancers, 95% are classified as rectal adenocarcinoma (READ). Emerging evidence suggests that long noncoding RNAs (lncRNAs) play a significant role in the development and progression of various cancers. In our study, we aimed to identify differentially expressed lncRNAs potentially associated with m6A and establish a risk assessment model to predict clinical outcomes for READ patients. METHODS: The READ dataset from the TCGA database was utilized in this study to synergistically and logically integrate m6A …and lncRNA, while employing bioinformatics technology for the identification of suitable biomarkers. A risk prediction model comprising m6A-associated lncRNAs was constructed to investigate the prognostic, diagnostic, and biological functional relevance of these m6A-related lncRNAs. RESULTS: Our research builds a composed of three related to m6A lncRNA rectal gland cancer prognosis model, and the model has been proved in the multi-dimensional can serve as the potential of the prognosis of rectal gland cancer biomarkers. Our study constructed a prognostic model of rectal adenocarcinoma consisting of three related m6A lncRNAs: linc00702, ac106900.1 and al583785.1. CONCLUSION: The model has been validated as a potential prognostic biomarker for rectal cancer in multiple dimensions, aiming to provide clinicians with an indicator to assess the duration of straight adenocarcinoma. This enables early detection of rectal cancer and offers a promising target for immunotherapy. Show more
Keywords: Long noncoding RNA (lncRNAs), rectal adenocarcinoma, prognostic model, m6A, immune microenvironment
DOI: 10.3233/CBM-230123
Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-15, 2024
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