Cancer Biomarkers最新文献

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.

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.

Purpose: It is widely accepted that there is a strong relationship between iron levels and cancer. This study aimed to investigate the relationship between serum ferritin levels and the severity and prognosis of gynecological malignant tumors.

Methods: This retrospective study included patients with gynecological malignant tumors at Sir Run Run Shaw Hospital in the Department of Obstetrics and Gynecology from January 2013 to June 2019. Patients were grouped according to their serum ferritin level: low (< 13 μg/L), normal (13-150 μg/L), and high (> 150 μg/L). Correlation analyses were performed between serum ferritin level and other factors. Cox univariable and multivariable analysis and Kaplan-Meier survival curves were used to assess the impact of ferritin on survival in patients with gynecologic tumors.

Results: The 402 total patients were divided into a low (n= 37), normal (n= 182), and high (n= 183) ferritin level group. Correlation analyses were performed that WBC, MCV, CRP, CA125, and CA153 were significantly positively correlated with serum ferritin level. The Kaplan-Meier survival curves revealed that of the three groups analyzed, the high serum ferritin level group had a significantly shorter survival time versus the normal and low serum ferritin level groups (log-rank P= 0.003). Univariable Cox regression analysis identified that patients with high serum ferritin levels had a significant correlation with risk of death compared to the patients with lower and normal serum ferritin levels. Serum ferritin was not found to be significant (HR = 0.792, 95% CI: 0.351-1.787, P= 0.574) in the multivariable Cox analysis.

Conclusion: Although this study did not find serum ferritin to be a significant independent prognosis indicator in gynecological malignant tumors, this study did identify that gynecological malignant tumor patients with high serum ferritin levels have significantly less survival time than patients with low or normal serum ferritin levels.

Background: Therapies for diffuse large B-cell lymphoma (DLBCL) are limited due to the diverse gene expression profiles and complicated immune microenvironments, making it an aggressive lymphoma. Beyond this, researches have shown that ferroptosis contributes to tumorigenesis, progression, and metastasis. We thus are interested to dissect the connection between ferroptosis and disease status of DLBCL. We aim at generating a valuable prognosis gene signature for predicting the status of patients of DLBCL, with focus on ferroptosis-related genes (FRGs).

Objective: To examine the connection between ferroptosis-related genes (FRGs) and clinical outcomes in DLBCL patients based on public datasets.

Methods: An expression profile dataset for DLBCL was downloaded from GSE32918 (https://www.ncbi.nlm.nih.gov/geo/ query/acc.cgi?acc=gse32918), and a ferroptosis-related gene cluster was obtained from the FerrDb database (http://www. zhounan.org/ferrdb/). A prognostic signature was developed from this gene cluster by applying a least absolute shrinkage and selection operator (LASSO) Cox regression analysis to GSE32918, followed by external validation. Its effectiveness as a biomarker and the prognostic value was determined by a receiver operator characteristic curve mono factor analysis. Finally, functional enrichment was evaluated by the package Cluster Profiler of R.

Results: Five ferroptosis-related genes (FRGs) (GOP1, GPX2, SLC7A5, ATF4, and CXCL2) associated with DLBCL were obtained by a multivariate analysis. The prognostic power of these five FRGs was verified by TCGA (https://xenabrowser.net/datapages/?dataset=TCGA.DLBC.sampleMap%2FHiSeqV2_PANCAN&host=https%3A%2F%2Ftcga.xenahubs.net&removeHub=https%3A%2F%2Fxena.treehouse.gi.ucsc.edu%3A44) and GEO (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse 32918) datasets, with ROC analyses. KEGG and GO analyses revealed that upregulated genes in the high-risk group based on the gene signature were enriched in receptor interactions and other cancer-related pathways, including pathways related to abnormal metabolism and cell differentiation.

Conclusion: The newly developed signature involving GOP1, GPX2, SLC7A5, ATF4, and CXCL2 has the potential to serve as a prognostic biomarker. Furthermore, our results provide additional support for the contribution of ferroptosis to DLBCL.

Colorectal cancer (CRC) is one of the most common digestive tract malignant tumors, which has a high mortality rate especially for patients with CRC recurrence. However, the pathological mechanism of recurrence of CRC is unclear. In this study, we integrated multiple cohort datasets and databases to clarify and verify potential key candidate biomarkers and signal transduction pathways in recurrence of CRC. As results, 628 DEGs were identified from GSE33113 and GSE2630 datasets and their function and pathway were analyzed. 14 hub genes related to CRC recurrence were screened from and their influence on survival were analyzed. Two key genes (IL1B and DDAH1) regarded as prognostic factors were further screened. Relapse-free survival results indicated the interaction between IL1B and DDAH1 genes and B cells was the most obvious and correlated with survival, with statistical significance (P< 0.05). Specially, cox regression analysis suggested that patients with T1 and N0 stages had a higher risk of recurrence than patients with T2 and N1. This work would provide potential value for prognosis, and would promote molecular targeting therapy for CRC recurrence.

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.

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 EGFRT790M mutations, overall survival (OS), and the clinical characteristics associated with LB positivity were determined.

Results: The prevalence of EGFRT790M 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.

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 importantOBJECTIVE: 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.