Cancer Biomarkers最新文献

Background: Cervical cancer (CC) is the fourth most common malignancy. The significant prognostic factors are tumor size and lympho-vascular space invasion. Considering that these are nonspecific factors, research has been aimed at finding a specific molecular marker related to a higher incidence of relapse and mortality in patients with CC.

Objective: Our study investigated the prognostic value of L1 cell adhesion molecule (L1CAM) expression in rare histological subtypes of cervical cancer (adenocarcinomas and adenosquamous cell carcinomas).

Methods: This is a single-institution retrospective study with 35 patients who underwent radical hysterectomy for early-stage cervical adenocarcinoma or adenosquamous cell carcinoma in 2007 through 2017. Paraffin sections of the tumor were used for L1CAM analysis by immunohistochemistry.

Results: L1CAM expression was positive in 15 (42.8%) of the 35 tumors. L1CAM expression did not differ significantly in regard to the stage of disease, tumor size, grading, or lymphovascular space invasion (LVSI) (p = 0.619, p = 0.341, p = 0.445, p = 0.999). Progression-free interval and overall survival did not differ between L1CAM-positive and L1CAM-negative groups (p = 0.704, p = 0.386, respectively).

Conclusions: In our study, L1CAM expression is not a negative prognostic factor associated with aggressive tumor behavior, recurrence risk and overall survival.

Background: The tumor microenvironment (TME) is increasingly recognized as a key player in colorectal cancer biology, however, its potential for improving diagnosis, prognosis, and treatment remains unclear. The major aim of this study is to explore the prognostic value of TME related gene in colorectal cancer. Method: Expression matrices and clinical data of colorectal cancer obtained from public databases were divided into TME relevant clusters according to immune characterization. A 11-gene molecular classifier was constructed based on differentially expressed genes between TME clusters and machine learning regression processes. Results: The efficacy and effectiveness of TME based prognostic signature (TPS) were examined in both the training and validation groups. The result indicated that TPS was able to serve as a superior prognosis indicator for colorectal cancer, alone or jointly with other clinical factors. Also, the study demonstrated that high risk colorectal cancer defined by TPS was considered to link with elevated immune infiltration, increased tumor mutation, and worse overall prognosis. Finally, potential therapeutic agents specialized for different risk subgroups of TPS was also identified to improve personalized treatment for colorectal cancer in the future. Conclusions: TPS might be a novel tool to improve the prognosis judgement and personalized treatment of the colorectal cancer in the future.

Background: Endometrial cancer (EC) is the fourth most common gynecologic malignancy among women. Histopathologic examination is considered gold-standard for diagnosis of EC. However, these examinations sometimes not be useful in distinguishing early stage types of EC.

Objectives: The current study aimed to investigate the clinicopathological significance of Lipocalin-2 (LCN2), matrix metalloproteinase-9 (MMP9), and ferritin in tumor progression.

Methods: A total of 98 patients (55 women newly diagnosed with early-stage endometrial cancer [study group] and 43 women with benign endometrial pathologies [control group]) were enrolled.

Results: There was a significant difference between diagnosis (p < 0.001), surgical procedure (p < 0.001), pathology (p = 0.002), stage (p < 0.001), lymphovascular invasion (LVI) (p = 0.002), myometrial invasion (p < 0.001), and staining intensity (p < 0.001), MMP9 (p = 0.023), LCN2 (p < 0.001), glucocorticoid (GC) (p = 0.048), tumor necrosis factor-alpha (TNF-α) (p = 0.044), menopause duration (p = 0.001), body weight (p < 0.001), and body mass index (BMI) (p < 0.001) were found to be higher, and ferritin levels (p = 0.047) were lower in the endometrial adenocarcinoma group compared to the benign endometrial pathologies.

Conclusion: LCN2, MMP9, and ferritin are practical markers in early cases of endometrial cancer. Serum LCN2 and MMP9 levels may be good clinical tools for the auxiliary diagnosis of early-stage endometrial cancer. Ferritin was also significantly sensitive. Therefore, detecting these markers together may be more beneficial for cancer diagnosis.

RNA-binding protein (RBP) plays pivotal roles in the malignant progression of cancer by regulating gene expression. In this paper, we aimed to develop RBP-based prognostic signature and identify critical hub RBPs in bladder cancer (BLCA). Firstly, a risk model based on differentially expressed RBP gens (DERBPs) between normal and tumor tissues was successfully established, which can predict the tumor stromal score and drug sensitivity. Then two another RBP risk models based on miRNA-correlated RBPs or lncRNA-correlated RBPs were also established, and RBMS3 was identified as the overlapping gene in the three models. Data from multiple bioinformatics databases revealed that RBMS3 was an independent prognostic factor for overall survival (OS), and was associated with an immunosuppressive tumor microenvironment (TME) in BLCA. Further, Single-cell RNA-Seq (scRNA-Seq) data and the human protein altas (HPA) database showed that RBMS3 expression (both mRNA and protein) were up-regulated in BLCA tumor and tumor stromal cells. Finally, RBMS3 was shown to be associated with worse response to BLCA immunotherapy. Overall, RBMS3 is a key prognostic RBP with TME remodeling function and may serve as a target for BLCA immunotherapy.

Background: The mitotic DNA integrity checkpoint signaling pathway is potentially involved in cancers that regulate genomic stability where protein kinases play a pivotal role. 16 total protein kinase genes are involved in this pathway: ATM, BRSK1, CDK1, CDK2, CHEK1, CHEK2, MAP3K20, NEK11, PLK1, PLK2, PLK3, PRKDC, STK33, TAOK1, TAOK2, and TAOK3. This study aims to provide pan-cancer profiles of the protein kinases in mitotic DNA integrity checkpoint signaling gene set for potential prognostic and diagnostic purposes, as well as future potential therapeutic targets for cancer in a clinical setting. Methods: Multi-omic data was acquired for the 16 genes; over 9000 samples of 33 types of cancer were analyzed to create pan-cancer profiles of SNV, CNV, methylation, mRNA expression, pathway crosstalk, and microRNA regulation networks. Results: The SNV profile showed that most of these genes have a high SNV mutation frequency across some cancer types, such as UCEC and SKCM. The CNVs of some of these genes are associated with the survival of UCEC, KIRP, and LGG. BRCA, KIRC, LUAD, and STAD might be affected by the mRNA expression of these genes which might involve regulation of copy number, methylation, and miRNA. In addition, these genes also cross-talk with some known cancer pathways. Conclusion: The protein kinases in mitotic DNA integrity checkpoint signaling may play a role in cancer development and, with adequate research, could potentially be developed as biomarkers for cancer diagnosis and prognosis. However, further efforts are necessary to validate their clinical value for diagnosis and prognosis and to develop practical applications in clinical settings. Nevertheless, these pan-cancer profiles offer a better overall understanding as well as useful information for future reference regarding mitotic DNA integrity checkpoint signaling in cancer.

BackgroundDistant metastasis (DM) remains the most commonly reported cause of death in patients with urothelial carcinoma of the bladder (UCB).ObjectiveWe aimed to develop a robust prognostic model to assess the risk of DM in patients with UCB.MethodsWe collected clinical data of 206 UCB patients treated with RC. Patients treated with RC between 2011-2015 that were enrolled as the training cohort (n = 105), while the patients between 2016-2019 were enrolled as the validation cohort (n = 101). Univariate and multivariate Cox regression models were used to identify independent risk factors associated with DM. We identified the variables by stepwise regression and established nomogram. We evaluated the nomograms using C-index, calibration and ROC curves. Decision curve analysis was performed to compare the net benefits between the nomogram and TNM staging. We divided the patients into high and low risk groups according to the nomogram and compared the DM between the groups.ResultsThe neutrophil-lymphocyte ratio (NLR) was an independent predictor of DM. We established nomogram by T-stage, N-stage and NLR. The C-index of the nomogram was 0.766 and 0.739 respectively in the two cohorts. In the training cohort, AUC for the nomogram at 1, 2 and 3 years was 0.816, 0.812 and 0.812, respectively. In the validation cohort, the AUC for the nomogram at 1, 2 and 3 years was 0.751, 0.757 and 0.716, respectively. The calibration curve was satisfactory. The nomogram has a higher clinical benefit compared to the TNM staging system. Kaplan-Meier curves showed that patients from the high-risk group had a higher probability of DM than patients from the low-risk group.ConclusionsNomograms established by NLR, T-stage and N-stage can accurately predict distant metastases in patients with UCB.

ObjectivesSignificant 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).MethodsWES 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.ResultsWe 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.ConclusionsOur 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.

BackgroundLung adenocarcinoma (LUAD) stands as a major respiratory malignancy with high mortality. With the advent of immunotherapy, new therapeutic avenues have emerged in cancer treatment.ObjectiveOur focus aimed at developing a CD8⁺ T cell-based immune gene prognostic model (CDIGPM) for LUAD, shedding light on the immunological aspects and the potential advantages of immunotherapy in distinct CDIGPM-defined LUAD categories.MethodsData from LUAD patients were extracted from the TCGA and GEO databases (GSE11969). The differentially expressed genes (DEGs) were intersected with immune genes from ImmPort and InnateDB, yielding 89 significant immune genes related to CD8⁺ T cells (CDIGs). Univariate Cox regression and LASSO regression analyses were performed on 10 hub CDIGs (ADM, CAV1, CTSL, HLA-DMB, HLA-DQA1, IGHM, PLSCR1, PTGDS, S100A16, and WFDC2). Furthermore, the immunological attributes and the immunotherapy efficacy in CDIGPM-defined categories were explored. Moreover, to support the findings of the bioinformatics analysis, fifteen LUAD patients' tumor and adjacent tissues were collected for qRT-PCR detection of CDIGPM-related genes.ResultsKaplan-Meier analysis revealed that the high-CDIGPM group exhibited significantly poorer overall survival (OS) trajectories, whereas the low-CDIGPM group showed more favorable OS trajectories, indicating a better prognosis. Age, tumor stage, and CDIGPM score were identified as independent prognostic factors. The high-CDIGPM group was enriched in pathways related to the cell cycle, focal adhesion, and cancer, while the low-CDIGPM group was associated with immune response-related pathways. The CDIGPM model effectively differentiated clinical subtypes in patients with LUAD. QRT-PCR detection of Clinical LUAD samples also validated the differentially expression of CDIGPM model related genes.ConclusionsThe study highlights the prognostic importance of CDIGs in LUAD using the CDIGPM model, linking age, stage and CDIGPM score to poor outcomes. The identified genes and pathways provide potential therapeutic targets, deepening our understanding of LUAD's molecular landscape.

Background: Pathological angiogenesis is crucial for tumor progression, thus targeting neovascularization is regarded as an effective strategy for cancer therapy. Vascular endothelial growth factor (VEGF), a specific pro-vascular endothelial regulator, contributes to aberrant tumor angiogenesis.

Objective: To identify sequence polymorphisms of VEGF gene and the effects on breast cancer.

Methods: Protein-DNA binding was validated by EMSA and ChIP assay. Gene expression levels were detected by qPCR and western blot. The CCK-8, wound healing and transwell assays were used to assess proliferation, migration, and invasion. Tube formation, CAM, ELISA and IHC assays were performed to evaluate tumor angiogenesis.

Results: A novel 18-bp indel mutation of the VEGF promoter was detected in breast cancer cases, and the deletion allele (DD) presented dominant distribution in patients comparing to the insert type (II). Further analysis revealed that the 18-bp deletion eliminated the recognition sites of GA binding protein alpha (GABPα), which was confirmed by binding experiments. Functionally, the GABPα expression is decreased in breast cancer tissues, and acts as a tumor suppressor to inhibit proliferation, migration, invasion and angiogenesis of breast cancer cells, accompanied by accelerated tumor cell apoptosis. In addition, consistent regulatory roles were investigated in mouse models in response to GABPα overexpression or knockdown as well. Mechanistically, we revealed that GABPα inhibited breast cancer progression and angiogenesis by downregulating VEGF transcription via the 18-bp promoter sequences.

Conclusions: Our findings provide insights into angiogenic targeted strategy aiming at GABPα-VEGF axis in clinical diagnosis and therapy of breast cancer.

BackgroundCircular RNA hsa_circ_0002346 has been implicated in the progression of various tumors, yet the functional role in breast cancer remains poorly understood. This study aimed to investigate the significance of hsa_circ_0002346 in breast cancer (BC).MethodsQuantitative reverse transcriptase polymerase chain reaction assays were performed to detect hsa_circ_0002346 expression in BC cell lins and 27 patients with BC. Then, siRNAs were used to knock down hsa_circ_0002346. And detecting function of downregulated hsa_circ_0002346 by proliferation colony formation, apoptosis assays, wound-healing assays and Transwell assays. Finally, we assess the levels of the EMT-associated proteins.ResultsOur findings suggest that hsa_circ_0002346 levels were significantly downregulated in breast cancer and may play a crucial role in regulating key cellular processes associated with cancer progression. The expression level of hsa_circ_0002346 was correlated with lymph node metastasis. The knockdown of hsa_circ_0002346 resulted in increased tumor cell proliferation, invasion, migration and decreased apoptosis. Additionally, alterations in the expression of EMT-associated proteins further support the hypothesis that hsa_circ_0002346 is implicated in the metastatic processes of breast cancer.Conclusionhsa_circ_0002346 emerges as a promising biomarker for breast cancer and a potential therapeutic target for future treatment strategies.