scholarly journals High expression of ABCG2 is associated with chemotherapy resistance of osteosarcoma

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Hao Shu ◽  
Bin Yuan ◽  
Yao Huang ◽  
Lei Wang ◽  
Bing He ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Time ◽  
Cell Lines ◽  
Chemotherapy Resistance ◽  
High Expression ◽  
Expression Level ◽  
Continuous Exposure ◽  
Overall Survival Time ◽  
Tumor Tissues ◽  
U2os Cells

Abstract Objectives Previous studies showed overexpression of ABCG2 in a variety of tumor tissues, which could potentially indicate the probability of chemotherapy resistance. This study aimed to reveal the role of ABCG2 in the development of chemotherapy resistance and the prognosis of osteosarcoma (OS). Methods Sixty-eight OS patients were included in this study. Tumor tissues were collected for each patient during surgery. DOX-resistant OS cell lines were induced by consecutive exposure of gradually increasing concentration of DOX to the parental cell lines. Lentivirus was used for the knockdown of ABCG2 in OS cells. Cells were treated with the gradient concentration of DOX, and the viability was assessed by CCK8 assay. Total RNA was isolated from the tumor tissues or tumor cells, and the expression of ABCG2 was analyzed by qPCR. The relationship between ABCG2 expression and clinicopathological characteristics of the patients was analyzed using Student’s t test or the Chi-square test. The overall survival time was calculated by the Kaplan-Meier method and analyzed by the log-rank test. p < 0.05 was considered statistically significant. Results DOX-resistant OS cells were successfully established through continuous exposure to DOX. Forty-eight hours after DOX exposure, the IC 50 value of DOX-resistant HOS cells and DOX-resistant U2OS was 3.5 μM and 3.25 μM, respectively. By contrast, those of the untreated HOS and U2OS cells were 1.15 μM and 0.93 μM, respectively (p < 0.01). The mRNA expression level of ABCG2 was significantly increased in DOX-resistant cell lines. The CCK-8 assay showed that the DOX-resistant HOS cells and DOX-resistant U2OS cells transfected with ShABCG2 were more sensitive to the DOX treatment than those transfected with ShCtrl. Analysis of gene expression in OS tissues showed remarkably higher expression of ABCG2 as compared with adjacent normal tissues (p < 0.01). Patients with high expression level of ABCG2 had obviously decreased overall survival time than the patients with normal expression (p < 0.01). Conclusions ABCG2 expression level was significantly associated with the resistance to chemotherapy and the overall survival of OS patients. ABCG2 may be a promising therapeutic target for OS patients.

scholarly journals High expression of ABCG2 is associated with doxorubicin resistance of osteosarcoma

2020 ◽  
Author(s):  
Hao Shu ◽  
Bin Yuan ◽  
Yao Huang ◽  
Lei Wang ◽  
Bing He ◽  
...  
Keyword(s):  
Survival Time ◽  
Cell Lines ◽  
Chemotherapy Resistance ◽  
Disease Free Survival ◽  
High Expression ◽  
Expression Level ◽  
Rank Test ◽  
Continuous Exposure ◽  
Tumor Tissues ◽  
U2os Cells

Abstract Objectives Previous studies showed overexpression of ABCG2 in a variety of tumor tissues, which could potentially indicate the probability of chemotherapy resistance. This study aimed to reveal the role of ABCG2 in the development of doxorubicin (DOX) resistance and the prognosis of OS. Methods 68 OS patients were included in this study. Tumor tissues were collected for each patient during surgery. DOX-resistant OS cell lines were induced by consecutive exposure of gradually increasing concentration of DOX to the parental cell lines. Lentivirus was used for the knockdown of ABCG2 in OS cells. Cells were treated with the gradient concentration of DOX and the viability was assessed by CCK8 assay. Total RNA was isolated from the tumor tissues or tumor cells, and the expression of ABCG2 was analyzed by qPCR. The relationship between ABCG2 expression and clinicopathological characteristics of the patients was analyzed using the Student’s t-test or the Chi-square test. Cumulative survival time was calculated by the Kaplan-Meier method and analyzed by the log-rank test. P < 0.05 was considered statistically significant. Results DOX-resistant OS cells were successfully established through continuous exposure to DOX. 48 h after DOX exposure, the IC 50 value of DOX-resistant HOS cells and DOX-resistant U2OS were 3.5 µM and 3.25 µM, respectively. By contrast, those of the untreated HOS and U2OS cells were 1.15 µM and 0.93 µM, respectively (p < 0.01). The mRNA expression level of ABCG2 was significantly increased in DOX-resistant cell lines. The CCK-8 assay showed that the DOX-resistant HOS cells and DOX-resistant U2OS cells transfected with ShABCG2 were more sensitive to the DOX treatment than those transfected with ShCtrl. Analysis of gene expression in OS tissues showed remarkably higher expression of ABCG2 as compared with adjacent normal tissues (p < 0.01). The disease-free survival time of patients with high expression level of ABCG2 had obviously decreased survival time than the patients with low expression (p < 0.01). Conclusions ABCG2 expression level was significantly associated with the resistance to DOX and the overall survival of OS patients. ABCG2 may become a promising therapeutic target for OS patients.

scholarly journals Identification of the Upregulation of MRPL13 as a Novel Prognostic Marker Associated with Overall Survival Time and Immunotherapy Response in Breast Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Hongshan Ye ◽  
Ning Zhang
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Survival Time ◽  
Prognostic Value ◽  
Expression Level ◽  
Occurrence Rate ◽  
Her2 Positive ◽  
Overall Survival Time ◽  
Human Cancers ◽  
Pan Cancer

Mitochondrial ribosomal protein (MRPL) genes have been reported to participate in many cellular processes, such as cell proliferation, apoptosis, and cell cycle. Meanwhile, the occurrence rate of breast cancer (BRCA) in China steadily increased. Exploring the prognostic value of MRPL genes in BRCA could provide novel biomarkers for BRCA. In this study, to identify prognosis-related genes in breast cancer, the P value and the hazard ratio (HR) of all genes are analyzed with TCGA database. We revealed higher expression level of CEL, PGK1, WNT3A, USP41, LINC02037, PCMT1, LRP11, MCTS1, TCP1, TMEM31, STK4-AS1, STXBP5, LOC100287036, SLC16A2, MRPL13, DERL1, and TARS was correlated to shorter OS time in BRCA. However, higher expression level of JCHAIN, KLRB1, and TNFRSF14 was correlated to longer OS time in BRCA. The further analysis demonstrated MRPL13 was overexpressed in BRCA. Subtype analysis showed that MRPL13 was overexpressed in luminal, HER2-positive BRCA, and TNBC samples and was highest in TNBC samples. Moreover, we revealed higher expression of MRPL13 was significantly correlated to shorter OS time and higher TMB levels in BRCA. Pan-cancer analysis further revealed the prognostic value of MRPL13 in human cancers. MRPL13 expression was significantly increased in multiple human cancers, such as bladder cancer, colon cancer, liver cancer, and prostate cancer. Pan-cancer TMB and overall survival time showed dysregulation of MRPL13 is significantly related to the OS and TMB levels in various cancers. These results further proved that MRPL13 may be a pan-cancer biomarker for predicting prognosis and the response to immunotherapy.

scholarly journals Upregulation of ARNTL2 is associated with poor survival and immune infiltration in clear cell renal cell carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Song Wang ◽  
Xueyou Ma ◽  
Yufan Ying ◽  
Jiazhu Sun ◽  
Zitong Yang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Wound Healing ◽  
Regression Analysis ◽  
Cell Lines ◽  
Cox Regression ◽  
High Expression ◽  
Expression Level ◽  
Cox Regression Analysis ◽  
Immune Infiltration ◽  
High Expression Level

Abstract Background Aryl hydrocarbon receptor nuclear translocator like 2 (ARNTL2) is a member of the PAS superfamily. Previous studies explored the carcinogenic roles of transcription factor ARNTL2 in human malignancies. However, its roles in ccRCC have not been elucidated. This study sought to explore the roles of ARNTL2 in ccRCC and determine its correlations with tumor immunity. Methods The expression of ARNTL2 was analyzed using the GEO, TCGA and GTEx database, and verified in ccRCC tissue samples and cell lines by qRT-PCR and western blot analysis. Kaplan–Meier survival curve analysis, Cox regression analysis (including univariate and multivariate analysis) was utilized to evaluate the prognostic values of ARNTL2. Potential biological mechanisms of ARNTL2 were explored using GSEA method. Colony formation and wound healing assays were conducted to explore the oncogenic role of ARNTL2 in ccRCC. ssGSEA and xCell algorithm were used to explore the correlation between ARNTL2 expression and tumor immune microenvironment (TIME). Results ARNTL2 was significantly upregulated in ccRCC tissues and cell lines compared to normal kidney tissues and cell line. Enhanced expression of ARNTL2 was strongly linked to advanced clinical stage and unfavorable overall survival in ccRCC. ARNTL2 was determined as an independent prognostic marker through cox regression analysis. A prognostic nomogram was constructed to predict 1-, 3- and 5-year overall survival of ccRCC patients by integrating ARNTL2 expression with other clinicopathologic variables. GSEA analysis showed that focal adhesion, T cell receptor, cell cycle, and JAK-STAT signaling pathway were significantly enriched in high ARNTL2 samples. Silencing of ARNTL2 suppressed the colony formation ability and wound healing efficacy of ccRCC cell lines. xCell analysis showed that high expression level of ARNTL2 exhibited an immune infiltration status similar to CD8 + inflamed ccRCC subtype, which was characterized by high infiltration level of CD8 + T cell and high expression level of the immune escape biomarkers such as PD-L1, PD-L2, PD1 and CTLA4. Conclusion ARNTL2 is an independent adverse predictor of ccRCC patient survival. High expression level of ARNTL2 is associated with immune infiltration, and may be a novel therapeutic target in ccRCC.

scholarly journals Long non-coding RNA ROR1-AS1 induces tumorigenesis of colorectal cancer by affecting Wnt/β-catenin signaling pathway

2019 ◽  
Vol 39 (11) ◽  
Author(s):  
Wei Wang ◽  
Weihong Zheng ◽  
Lei Zhang ◽  
Ke Li
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Survival Time ◽  
Signaling Pathway ◽  
Malignant Tumors ◽  
Expression Level ◽  
Migration And Invasion ◽  
Tissue Samples ◽  
Overall Survival Time

Abstract Recent studies have discovered that long noncoding RNAs (lncRNAs) play an important role in malignant tumors. In this research, lncRNA ROR1-AS1 was selected to identify how it affects the development of colorectal cancer (CRC). ROR1-AS1 expression was detected by RT-qPCR in CRC tissue samples. ROR1-AS1 expression level and patients’ overall survival time were analyzed. Functional experiments were conducted to identify the changes of biological behaviors in CRC cells after knockdown of ROR1-AS1. Moreover, we also explored the underlying mechanism. Detection of ROR1-AS1 expression level in patients’ tissues showed that ROR1-AS1 was higher in CRC tissues than that in adjacent ones. ROR1-AS1 expression was negatively associated with patients’ overall survival time. Cell growth ability was inhibited due to knockdown of ROR1-AS1 in vitro. Moreover, cell migration and invasion were repressed after ROR1-AS1 knockdown. Furthermore, due to knockdown of ROR1-AS1, the targeted proteins in Wnt/β-catenin signaling pathway were suppressed. These results suggest that ROR1-AS1 could enhance cell metastasis and proliferation via inducing Wnt/β-catenin signaling pathway, which might offer a potential therapeutic target in CRC.

scholarly journals Up-regulation of KLF17 expression increases the sensitivity of gastric cancer to 5-fluorouracil

2021 ◽  
Vol 35 ◽  
pp. 205873842110109
Author(s):  
Zhao-jie An ◽  
Yong Li ◽  
Bi-bo Tan ◽  
Qun Zhao ◽  
Li-qiao Fan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Western Blot ◽  
Cell Lines ◽  
Regional Lymph Node ◽  
Chemotherapy Resistance ◽  
B Cell Lymphoma ◽  
Tnm Staging ◽  
Expression Level ◽  
Normal Tissues ◽  
Tumor Tissues

It has been reported that the expression of Krüppel-like factor 17 (KLF17) was associated with the occurrence, development, invasion, metastasis and chemotherapy resistance of various tumors. However, the detailed mechanisms by which KLF17 promotes chemotherapy resistance in gastric cancer (GC) have not been fully investigated. In the present study, we collected the GC tissues and non-tumor tissues (matched adjacent normal tissues with corresponding GC tissues) of 60 GC patients, used qRT-PCR, Western blot and immunohistochemistry assay to analyze the relationship between the expression of KLF17 and the clinical pathological data of the patients. The effect of KLF17 on the sensitivity of GC cell lines to 5-fluorouracil (5-FU), and the potential mechanism were detected by MTS assay, Flow cytometry assay, and Western blot. Compared with non-tumor tissues, the expression level of KLF17 in GC tissue was significantly down-regulated, and the expression level of KLF17 in GES-1 cell line and GC cell lines also had a similar trend. Down-regulated expression of KLF17 is related to tumor size, invasion, regional lymph node metastasis, and TNM staging. Furthermore, through upregulating the expression of KLF17, the sensitivity of BGC-823 and SGC-7901 cell lines to 5-FU was obviously increased. Mechanistically, upregulation the expression of KLF17 can inhibit the expressions of P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and B-Cell lymphoma-2 (BCL-2), which have been reported to be associated with drug resistance and cell proliferation. Collectively, these data implied that KLF17 has the biological effect of inhibiting chemotherapy resistance of GC, and it could be a potential strategy for the GC chemotherapy resistance.

scholarly journals Involvement of Indoleamine 2,3-Dioxygenase in Impairing Tumor-Infiltrating CD8+T-Cell Functions in Esophageal Squamous Cell Carcinoma

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Ge Zhang ◽  
Wan-Li Liu ◽  
Lin Zhang ◽  
Jun-Ye Wang ◽  
Miao-Huan Kuang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Survival Time ◽  
Squamous Cell ◽  
Tumor Immune Escape ◽  
Cell Functions ◽  
Indoleamine 2,3 Dioxygenase ◽  
Overall Survival Time

The indoleamine 2,3-dioxygenase-(IDO-) mediated microenvironment plays an important role in tumor immune escape. However, the inhibitory effects of IDO on the CD8+tumour-infiltrating lymphocytes (CD8+TILs) in esophageal squamous cell carcinoma (ESCC) have not been clarified yet. Here, we found that the level of IDO expression in ESCC tumor specimens correlated with a reduction in the number of CD8+TILs. Patients with high IDO expression and a low number of CD8+TILs had significantly impaired overall survival time. IDO expression and functional enzyme activity in ESCC cell lines could be induced by IFNγ. When exposed to the milieu generated by IDO-expressing Eca109 cells, the CD8+TILs were suppressed in proliferation, and their cytolytic functions against target tumor cells were lost. These results suggested that impairing CD8+TIL functions by IDO expressed in ESCC possibly contributed to the finding that patients with higher IDO expression have more aggressive disease progression and shorter overall survival time.

scholarly journals Endocrine response and outcome in 14 cats with insulin resistance and acromegaly treated with stereotactic radiosurgery (17 Gy)

2022 ◽  
pp. 1-8
Author(s):  
Maegan L. Watson-Skaggs ◽  
Tracy L. Gieger ◽  
Hiroto Yoshikawa ◽  
Michael W. Nolan
Keyword(s):  
Insulin Resistance ◽  
Overall Survival ◽  
Adverse Effects ◽  
Survival Time ◽  
Stereotactic Radiosurgery ◽  
Insulin Dose ◽  
Exogenous Insulin ◽  
Endocrine Response ◽  
Overall Survival Time ◽  
Insulin Requirements

Abstract OBJECTIVE To describe clinical outcomes in cats with insulin resistance and acromegaly treated with stereotactic radiosurgery (SRS). ANIMALS 14 client-owned cats. PROCEDURES Medical records of cats with insulin resistance and acromegaly treated with SRS (17 Gy) between August 2013 and November 2019 at a single institution were reviewed. Kaplan-Meier analysis was used to evaluate overall survival time. RESULTS Acute adverse effects of SRS included somnolence (n = 2) and alopecia (1). Delayed adverse effects of SRS included unspecified neurologic complications (n = 1; 481 days), seizures (1; 1,541 days), and hypothyroidism (1; 64 days). Exogenous insulin requirements decreased in 10 of the 14 cats, with a median time to lowest insulin dose of 399 days (range, 42 to 879 days). Complete diabetic remission was achieved in 3 cats. The median overall survival time was 741 days (95% CI, 353 to 1,129 days). Six cats were still alive at the end of the study period, with a median follow-up time of 725 days. In 7 of the 8 cats that had died, death was presumptively attributed to acromegaly owing to continued insulin resistance, organ failure, or altered neurologic status. CLINICAL RELEVANCE The SRS protocol was well tolerated and associated with survival times similar to those reported previously. Most cats had decreased exogenous insulin requirements after SRS. Latency to an endocrine response was highly variable, emphasizing the need for careful ongoing diabetic monitoring of acromegalic cats after pituitary gland irradiation.

The Clinical and Prognostic Significance of Protein Arginine Deiminases 2 and 4 in Colorectal Cancer

Pathobiology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Mohamed Gijon ◽  
Rachael L. Metheringham ◽  
Michael S. Toss ◽  
Samantha J. Paston ◽  
Lindy G. Durrant
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Survival Time ◽  
Patient Survival ◽  
Prognostic Significance ◽  
High Expression ◽  
Related Protein ◽  
Post Translational Modification

<b><i>Introduction:</i></b> Protein arginine deiminases (PADIs) are a family of enzymes that catalyse the post-translational modification of proteins. Association between PADI expression and clinicopathology, protein expression, and outcome was determined. <b><i>Methods:</i></b> PADI2 and PADI4 expression was assessed immunohistochemically in a cohort of colorectal cancer (CRC) patients. <b><i>Results:</i></b> CRC tissues expressed variable levels of PADI2 which was mainly localised in the cytoplasm and correlated with patient survival (<i>p</i> = 0.005); high expression increased survival time from 43.5 to 67.6 months. Expression of cytoplasmic PADI2 correlated with the expression of nuclear β catenin, PADI4, and alpha-enolase. In contrast, expression of nuclear PADI2 correlated with a decrease in survival (<i>p</i> = 0.010), with high expression decreasing survival from 76.4 to 42.9 months. CRC tissues expressed variable levels of PADI4 in both the nucleus and cytoplasm. Expression of cytoplasmic PADI4 correlated with survival (<i>p</i> = 0.001) with high expression increasing survival time from 48.1 to 71.8 months. Expression of cytoplasmic PADI4 correlated with expression of nuclear β catenin, alpha-enolase (<i>p</i> ≤ 0.0001, <i>p</i> = 0.002), and the apoptotic related protein, Bcl-2. Expression of nuclear PADI4 also correlated with survival (<i>p</i> = 0.011), with high expression of nuclear PADI4 increasing survival time from 55.4 to 74 months. Expression of nuclear PADI4 correlated with p53, alpha-enolase, and Bcl-2. Multivariate analysis showed that TNM stage, cytoplasmic PADI2, and PADI4 remained independent prognostic factors in CRC. Both PADI2 and PADI4 are good prognostic factors in CRC. <b><i>Conclusion:</i></b> High expression of cytoplasmic PADI2, PADI4, and nuclear PADI4 were associated with an increase in overall survival.

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