Paclitaxel Promotes Tumor-Infiltrating Macrophages in Breast Cancer

Objective: Breast cancer remains the most threatening triggers of cancer death in women. Drug resistance inevitably leads to the weakness of treatment for breast cancer. Macrophages, as one of the most abundant immune cells in tumor immune-infiltrating microenvironment, involves in cell survival, migration, and invasion of breast cancer. Methods: In this study, we compared the proportions of macrophages in patients with breast cancer with and without paclitaxel treatment, and investigated the targeted genes associated with macrophages for paclitaxel response. To explore the relationship between drug-related genes and breast cancer prognosis, survival analysis based on the drug-related genes were performed by website of Kaplan-Meier plotter with the threshold of significant P value < .05. Results: Compared to the normal samples, we revealed that paclitaxel significantly enhanced the ratio of macrophages in the tumor microenvironment. Furthermore, the expression of 3 drug-related genes (IFT46, PEX11A, and TMEM223) were significantly negatively associated with the proportions of macrophages. And it is worth to notice that PEX11A and TMEM223 were associated with better progression-free survival outcomes of patients with breast cancer. Moreover, PEX11A was associated with longer overall survival time of breast cancer. Conclusion: Taken all together, all the findings support to gain a better understanding to the development of more effective therapies targeted with paclitaxel.

Download Full-text

KLHL5 Is a Prognostic-Related Biomarker and Correlated With Immune Infiltrates in Gastric Cancer

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2020.599110 ◽

2020 ◽

Vol 7 ◽

Author(s):

Qiulin Wu ◽

Guobing Yin ◽

Jinwei Lei ◽

Jiao Tian ◽

Ailin Lan ◽

...

Keyword(s):

Gastric Cancer ◽

Clinical Outcomes ◽

Immune Cell ◽

Progression Free Survival ◽

Differentially Expressed ◽

Free Survival ◽

Kaplan Meier ◽

Patient Prognosis ◽

The Relationship ◽

Kaplan Meier Plotter

Background: KLHL5 (Kelch Like Family Member 5) is differentially expressed in gastric cancer, but its correlation with prognosis and functioning mechanism in gastric cancer remain unclear.Methods: The Oncomine database and TIMER were employed to appraise the KLHL5 expression in a variety of cancers. The correlation between KLHL5 expression and patient prognosis was extracted from the Kaplan–Meier plotter, GEPIA, and PrognoScan database. Then the relationship between KLHL5 expression and inflammatory infiltrate profiles was inquired by TIMER. Finally, GEPIA and TIMER were explored for the correlative significance between KLHL5 expression and immune cell–related marker sets.Results: KLHL5 was found to be differentially expressed and correlated with clinical outcomes in several types of cancers in the TCGA database. Especially, KLHL5 mRNA expression was upregulated and correlated with poorer overall survival and progression-free survival in gastric cancer. Moreover, elevated KLHL5 expression was significantly related with patient node stage, infiltration level, and expression of multiple immune marker sets.Conclusions: These results implicate that KLHL5 expression is closely linked with patient clinical outcomes and the microenvironmental infiltration level in different neoplasms. This indicates that KLHL5 is a modulator in infiltrate recruitment, shaping the landscape of immune cell infiltration. Thus, it represents an eligible prognostic predictor for gastric malignancy.

Download Full-text

NOVEL PLASMA GLYCOPROTEIN BIOMARKERS PREDICT PROGRESSION-FREE SURVIVAL IN SURGICALLY RESECTED CLEAR CELL RENAL CELL CARCINOMA

10.1101/2022.01.11.21268517 ◽

2022 ◽

Author(s):

Daniel Serie ◽

Amanda A Myers ◽

Daniela A Haehn ◽

Alexander Parker ◽

Essa Bajalia ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Differential Expression ◽

Renal Cell ◽

Clear Cell ◽

Progression Free Survival ◽

P Value ◽

Cell Renal Cell Carcinoma ◽

Free Survival ◽

Kaplan Meier

Introduction: Limited data exists on utilization of protein post-translational modifications as biomarkers for clear cell renal cell carcinoma (ccRCC). We employed high-throughput glycoproteomics to evaluate differential expression of glycoprotein-isoforms as novel markers for ccRCC progression-free survival (PFS). Methods: Plasma samples were obtained from 77 patients treated surgically for ccRCC. Glycoproteomic analyses were carried out after liquid chromatography tandem mass spectrometry. Age-adjusted Cox proportional hazard models were constructed to evaluate PFS. Optimized Harrells c-index was employed to dichotomize the collective for the construction of Kaplan-Meier curves. Results: The average length of follow-up was 3.4 (range: 0.04-9.83) years. Glycoproteomic analysis identified 39 glycopeptides and 14 non-glycosylated peptides that showed statistically significant (false discovery rate p ≤0.05) differential expression associated with PFS. Five of the glycosylated peptides conferred continuous hazard ratio of > 6 (range 6.3-11.6). These included prothrombin A2G2S glycan motif (HR=6.47, P=9.53E-05), immunoglobulin J chain FA2G2S2 motif (HR=10.69, P=0.001), clusterin A2G2 motif (HR=7.38, P=0.002), complement component C8A A2G2S2 motif (HR=11.59, P=0.002), and apolipoprotein M glycopeptide with non-fucosylated and non-sialylated hybrid-type glycan (HR=6.30, P=0.003). Kaplan-Meier curves based on dichotomous expression of these five glycopeptides resulted in hazard ratios of 3.9-10.7, all with p-value < 0.03. Kaplan-Meyer plot using the multivariable model comprising 3 of the markers yielded HR of 11.96 (p <0.0001). Conclusion: Differential glyco-isoform abundance of plasma proteins may be a useful source of biomarkers for the clinical course and prognosis of ccRCC.

Download Full-text

Identification of Flap Endonuclease 1 With Diagnostic and Prognostic Value in Breast Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.603114 ◽

2021 ◽

Vol 11 ◽

Author(s):

Min Wu ◽

Pan Zhang ◽

Penghui Wang ◽

Zhen Fang ◽

Yaqin Zhu

Keyword(s):

Breast Cancer ◽

Prognostic Marker ◽

Prognostic Value ◽

Diagnostic Value ◽

Roc Curve Analysis ◽

Free Survival ◽

Flap Endonuclease 1 ◽

Normal Tissues ◽

Kaplan Meier ◽

Kaplan Meier Plotter

ObjectiveThis study aims to identify the potential value of flap endonuclease 1 (FEN1) as a diagnostic and prognostic marker for breast cancer (BC).MethodsELISA was used to measure serum FEN1 levels and ECLIA for CA153 and CEA levels. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value. Oncomine and UALCAN databases were used to analyze the differences in FEN1 mRNA and protein expressions. Kaplan-Meier Plotter database was then used to assess the prognostic value.ResultsBioinformatics analysis showed that the FEN1 mRNA and protein levels were significantly higher in BC tissues than in normal tissues. FEN1 was detected in culture medium of BC cell lines and serum FEN1 concentrations were significantly increased in BC patients than in cancer-free individuals. Besides, FEN1 exhibited higher diagnostic accuracy (AUC values>0.800) than CA153 and CEA for distinguishing BC patients, especially early BC, from the healthy and benign groups, or individually. Additionally, serum FEN1 levels were significantly associated with the stage (P=0.001) and lymph invasion (P=0.016), and serum FEN1 levels were increased with the development of BC. Furthermore, serum FEN1 levels were significantly decreased in post-operative patients than in pre-operative patients (P=0.016). Based on the Kaplan-Meier Plotter database, the survival analysis indicated that FEN1 overexpression was associated with poor prognoses for overall survival (OS), relapse-free survival (RFS), and distant metastasis-free survival (DMFS) in BC patients.ConclusionFEN1 might be a novel diagnostic and prognostic marker for BC.

Download Full-text

The Alterations and Potential Roles of MCMs in Breast Cancer

Journal of Oncology ◽

10.1155/2021/7928937 ◽

2021 ◽

Vol 2021 ◽

pp. 1-17

Author(s):

Xinyu Liu ◽

Ying Liu ◽

Qiangshan Wang ◽

Siqi Song ◽

Lingjun Feng ◽

...

Keyword(s):

Breast Cancer ◽

Gene Network ◽

Relapse Free Survival ◽

Minichromosome Maintenance ◽

Free Survival ◽

Oncomine Database ◽

Kaplan Meier ◽

Eukaryotic Dna ◽

Coexpressed Genes ◽

Kaplan Meier Plotter

The minichromosome maintenance (MCM) protein family plays a key role in eukaryotic DNA replication and has been confirmed to be associated with the occurrence and progression of many tumors. However, the expression levels, functions, and prognostic values of MCMs in breast cancer (BC) have not been clearly and systematically explained. In this article, we studied the transcriptional levels of MCMs in BC based on the Oncomine database. Kaplan-Meier plotter was used to analyze prognostic value of MCMs in human BC patients. Furthermore, we constructed a MCM coexpression gene network and performed functional annotation analysis through DAVID to reveal the functions of MCMs and coexpressed genes. The data showed that the expression of MCM2–8 and MCM10 but not MCM1 and MCM9 was upregulated in BC. Kaplan-Meier plotter analysis revealed that high transcriptional levels of MCM2, MCM4–7, and MCM10 were significantly related to low relapse-free survival (RFS) in BC patients. In contrast, high levels of MCM1 and MCM9 predicted high RFS for BC patients. This study suggests that MCM2, MCM4–7, and MCM10 possess great potential to be valuable prognostic biomarkers for BC and that MCM1 and MCM9 may serve as potential treatment targets for BC patients.

Download Full-text

Gasdermin D as a potential prognosis and treatment response prediction biomarker for invasive breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e12548 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e12548-e12548

Author(s):

Xianghou Xia ◽

Wenjuan Yin ◽

Jiefei Mao ◽

Jiejie Hu ◽

Dehong Zou ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Invasive Breast Cancer ◽

Response Prediction ◽

Chemotherapy Response ◽

Breast Cancer Patients ◽

Free Survival ◽

Kaplan Meier ◽

Kaplan Meier Plotter ◽

Treatment Response Prediction

e12548 Background: Pyroptosis is a type of inflammatory cell death mediated by gasdermins. Pyroptosis is critical for macrophage against pathogen infection. Recently growing evidences show that pyroptosis may affect development and progression of many cancers. We aim to explore the expression and related function of pyroptosis executioner Gasdermin D (GSDMD) in breast cancer. Methods: We investigated the expression level of GSDMD using TNM plotter and Breast Cancer landscape proteome with TCGA, GTEx and TARGET databases, and the prognostic value of GSDMD in invasive breast cancer using Kaplan-Meier plotter with TCGA, GEO and EGA databases. The treatment response prediction values of GSDMD in invasive breast were calculated using ROC-plotter with GEO database. Further validation of the prognostic value and chemotherapy response prediction value of GSDMD were carried out with immunohistochemical staining on tissues from 165 cases of breast cancer patients receiving neoadjuvant chemotherapy in our cancer center. Results: TNM plotter and breast cancer landscape proteome portal analysis shows that overall expression level of GSDMD in invasive breast cancer tissue is 1.67 folds higher than it is in breast normal tissues ( p=1.05*e-06). Expression of GSDMD in LuminalB subtype (p=0.019) and Her2 subtype(p=0.04) is significantly higher than it is in TNBC subtype. Calculations with Kaplan-Meier plotter show expression of GSDMD is negatively correlated with overall survival(OS), HR=0.61(0.4−0.95) p=0.027 and relapse free survival (RFS), HR =0.65(0.58−0.63), p=8.7*e-14 and distant metastasis free survival (DMFS) HR =0.75(0.61−0.91), p=0.0038 in breast cancer patients. ROC-plotter calculations show high GSDMD expression is a powerful endocrine therapy (AUC=0.731 p=6*e-09 ) and chemotherapy response (AUC=0.64 p=8*e-05 ) predictor based on 5-year RFS in overall breast cancer patients. Our IHC staining analysis shows consistent prognostic and chemotherapy prediction value of GSDMD expression in TNBC patients. Conclusions: In conclusion, our findings suggest that high expression of GSDMD is positively correlated with prognosis and therapeutic response in breast cancer. GSDMD is a promising prognostic marker and therapeutic response predictor in invasive breast cancer.

Download Full-text

Mining expression and prognosis of FOLR1 in ovarian cancer by using Oncomine and Kaplan-Meier plotter

Pteridines ◽

10.1515/pteridines-2019-0020 ◽

2019 ◽

Vol 30 (1) ◽

pp. 158-164

Author(s):

Qingyuan Su ◽

Qingyuan Lv ◽

Ruijin Wu

Keyword(s):

Ovarian Cancer ◽

Mrna Expression ◽

Ovarian Tumor ◽

Ovarian Tissue ◽

Progression Free Survival ◽

Free Survival ◽

Normal Ovarian Tissue ◽

Oncomine Database ◽

Kaplan Meier ◽

Kaplan Meier Plotter

Abstract Objective: To further explore folate receptor 1 (FOLR1) gene expression in ovarian cancer and its association with patients’ prognosis by deep mining the Oncomine and Kaplan-Meier plotter databases. Methods: FOLR1 mRNA expression data of ovarian cancer were retrieved from the Oncomine database and further analyzed by comparing tumor to healthy tissue. The prognostic value of FOLR1 in ovarian cancer was analyzed by Kaplan-Meier Plotter, an online survival analysis database. Results A total of 439 studies were included in the Oncomine database in multiple types of cancers. Of the 439 studies, there were 54 with statistical differences for the expression of FOLR1, 19 with increased expression of FOLR1 and 35 with decreased expression comparing ovarian cancer to normal ovary tissue. After searching the Oncomine database, six datasets were discovered comparing the mRNA expression in ovarian tumor to healthy tissue. FOLR1 mRNA expression in ovarian tumor was significantly higher than that of normal ovarian tissue (all p<0.05). The Kaplan-Meier Plotter database analyzed the correlation between FOLR1 expression and ovarian cancer patient’s prognosis. A significant difference of progression-free survival between FOLR1 high and low expressing groups was found in ovarian cancer patients (HR=1.14, 95%CI: 1.00-1.29, p=0.043). However, the overall survival was not statistically different between high and low FOLR1 expressing patients (HR=0.95, 95%CI: 0.84-1.09, p=0.48). Conclusion FOLR1 mRNA was found to be highly expressed in ovarian tumor compared to normal ovarian tissue. Elevated FOLR1 mRNA expression was associated with the poor progression-free survival.

Download Full-text

Real-world effectiveness outcomes in patients diagnosed with metastatic triple-negative breast cancer

Future Oncology ◽

10.2217/fon-2020-1021 ◽

2020 ◽

Author(s):

Karen E Skinner ◽

Amin Haiderali ◽

Min Huang ◽

Lee S Schwartzberg

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Cox Regression ◽

Unmet Need ◽

Progression Free Survival ◽

Free Survival ◽

Regression Methods ◽

Kaplan Meier ◽

Community Oncology

Aim: This study examined treatment patterns and effectiveness outcomes of patients with metastatic triple-negative breast cancer (mTNBC) from US community oncology centers. Materials & methods: Eligible patients were females, aged ≥18 years, diagnosed with mTNBC between 1 January 2010 and 31 January 2016. Kaplan–Meier and Cox regression methods were used. Results: Sample comprised 608 patients with average age of 57.5 years and 505/608 patients (83.1%) received systemic treatment. Overall survival (OS) from first-line treatment found that African–American patients had shorter OS than White (9.3 vs 13.7 months; hazard ratio: 1.35; p = 0.006). Conclusion: More than 15% of women with mTNBC were not treated, indicating a high unmet need. Overall prognosis remains poor, which highlights the opportunity for newer therapies to improve progression-free survival and OS.

Download Full-text

Genetic variants in MIR17HG affect the susceptibility and prognosis of glioma in a Chinese Han population

10.21203/rs.2.20791/v2 ◽

2020 ◽

Author(s):

Jigao Feng ◽

Yibin Ouyang ◽

Dedong Xu ◽

Qinglong He ◽

Dayuan Liu ◽

...

Keyword(s):

Progression Free Survival ◽

Chinese Han Population ◽

Migration And Invasion ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Han Population ◽

Kaplan Meier ◽

Hazard Ratios ◽

The Relationship

Abstract Background: lncRNA MIR17HG was upregulated in glioma, and participated in promoting proliferation, migration and invasion of glioma. However, the role of MIR17HG polymorphisms in the occurrence and prognosis of glioma is still unclear.Methods: In the study, 592 glioma patients and 502 control subjects were recruited. Agena MassARRAY platform was used to detect the genotype of MIR17HG polymorphisms. Logistic regression analysis was used to evaluate the relationship between MIR17HG single nucleotide polymorphisms (SNPs) and glioma risk by odds ratio (OR) and 95% confidence intervals (CIs). Kaplan–Meier curves, Cox hazards models were performed for assessing the role of these SNPs in glioma prognosis by hazard ratios (HR) and 95% CIs.Results: We found that rs7318578 (OR = 2.25, p = 3.18´10-5) was significantly associated with glioma susceptibility in the overall participants. In the subgroup with age < 40 years, rs17735387 (OR = 1.53, p = 9.05´10-3) and rs7336610 (OR = 1.35, p = 0.016) were related to the higher glioma susceptibility. More importantly, rs17735387 (HR = 0.82, log-rank p = 0.026) were associated with the longer survival of glioma patients. The GA genotype of rs17735387 had a better overall survival (HR = 0.75, log-rank p = 0.013) and progression free survival (HR = 0.73, log-rank p = 0.032) in patients with Ⅰ-Ⅱ glioma. We also found that rs72640334 was related to the poor prognosis (HR = 1.49, Log-rank p = 0.035) in female patients. In the subgroup of patients with age ³ 40 years, rs17735387 was associated with a better prognosis (HR = 0.036, Log-rank p = 0.002).Conclusion: Our study firstly reported that MIR17HG rs7318578 was a risk factor for glioma susceptibility and rs17735387 was associated with the longer survival of glioma among Chinese Han population, which might help to enhance the understanding of MIR17HG gene in gliomagenesis.

Download Full-text

ASRGL1 Correlates With Immune Cell Infiltration in Hepatocellular Carcinoma and Can Serve as a Prognostic Biomarker

Frontiers in Oncology ◽

10.3389/fonc.2021.680070 ◽

2021 ◽

Vol 11 ◽

Author(s):

Cailin Xue ◽

Peng Gao ◽

Xiaohan Cui ◽

Xudong Zhang ◽

Jin Lei ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Mrna Expression ◽

Immune Cell ◽

Progression Free Survival ◽

Free Survival ◽

Kegg Pathways ◽

Interactive Analysis ◽

Kaplan Meier ◽

Hydrolysis Of ◽

Kaplan Meier Plotter

BackgroundThe enzyme L-asparaginase (ASRGL1) catalyzes the hydrolysis of L-asparagine (Asn) to L-aspartic acid (Asp) and ammonia. Numerous studies have shown a strong correlation between ASRGL1 expression and tumorigenesis. However, the expression and biological function of ASRGL1 in hepatocellular carcinoma (HCC) are still unclear.MethodsWe explored the mRNA expression of ASRGL1 in HCC using the HCCDB, Oncomine, and TIMER 2.0 databases. Western blotting and immunohistochemical analyses were also used to determine the mRNA expression of ASRGL1 in HCC. LinkedOmics was used to analyze the genes co-expressed with ASRGL1 and regulators including kinases, miRNAs, and transcription factors. The Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the co-expressed genes were also investigated using LinkedOmics. The correlation between ASRGL1 expression and immune infiltrates was analyzed using the TIMER 2.0 and Gene Expression Profiling Interactive Analysis (GEPIA) databases. The effects of ASRGL1 expression on patient outcome were investigated using the UALCAN and GEPIA databases, and the Kaplan–Meier plotter. c-Bioportal was used to explore the mutations of ASRGL1 in HCC.ResultsCompared with the adjacent tissues, ASRGL1 was upregulated in HCC. High ASRGL1 expression in HCC indicated poor relapse-free survival, progression-free survival, disease-specific survival, and overall survival. The expression of ASRGL1 was significantly correlated with infiltrating levels of B cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in HCC.ConclusionOur findings suggest that ASRGL1 is overexpressed in HCC and that ASRGL1 expression was significantly correlated with immune infiltration in HCC and prognosis. Therefore, ASRGL1 may serve as a biomarker for the early diagnosis and treatment of HCC.

Download Full-text