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

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.

2020 ◽  
Vol 9 (7) ◽  
pp. 205846012093874
Author(s):  
Yukinori Okada ◽  
Mariko Kobayashi ◽  
Mio Shinozaki ◽  
Tatsuyuki Abe ◽  
Yoshihide Kanemaki ◽  
...  

Background Breast cancer has a poor prognosis due to the high risk of distant metastasis. Purpose To identify the prognosticators of brain metastasis from breast cancer treated by whole-brain radiotherapy. Material and Methods We evaluated patients diagnosed with primary brain metastasis without carcinomatous meningitis from breast cancer and had undergone whole-brain radiotherapy as initial treatment between 1 January 2010 and 30 September 2019. We investigated associations between overall survival time from diagnosis using cranial contrast-enhanced magnetic resonance imaging (MRI)/computed tomography (CT) and the following parameters: (i) age; (ii) sex; (iii) time to appearance of brain metastasis; (iv) other metastasis at appearance of brain metastasis; (v) blood test; (vi) symptoms at time of brain metastasis; (vii) whole-brain radiotherapy dose; (viii) whether whole-brain radiotherapy was completed; (ix) course of chemo- or radiotherapy; (x) subtype; (xi) additional irradiation after whole-brain radiotherapy; (xii) pathology; and (xiii) imaging findings. Results We evaluated 29 consecutive female patients (mean age 55.2 ± 12.1 years). Median overall survival time after diagnosis on cranial contrast-enhanced MRI/CT was 135 days (range 16–2112 days). Multivariate stepwise analysis of the three parameters of lactate dehydrogenase, dose, and subtype identified the following significant differences: Hazard Ratio (HR) for dose (discontinued, 30 Gy/10 fractions, 31.5 Gy/11 fractions, 32.5 Gy/11 fractions, 37.5 Gy/15 fractions) was 0.08 (95% confidence interval [CI] 0.02–0.30, P < 0.01), and HR for subtype (luminal, HER2, triple-negative) was 2.70 (95% CI 1.16–6.243, P < 0.01). Conclusion HER2-type and 37.5 Gy/15 fractions are good prognostic factor after whole-brain radiotherapy in breast cancer with brain metastases.


2019 ◽  
Vol 39 (11) ◽  
Author(s):  
Wei Wang ◽  
Weihong Zheng ◽  
Lei Zhang ◽  
Ke Li

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.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Hao Shu ◽  
Bin Yuan ◽  
Yao Huang ◽  
Lei Wang ◽  
Bing He ◽  
...  

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.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Hesham Ahmed ElGhazaly ◽  
Manal Mohamed El-Mahdy ◽  
Azza Mohamed Adel ◽  
Nermeen Mostafa ◽  
Aya Magdy Kamal Ali

Abstract Background TNBC comprises a distinct disease entity with a unique microenvironment of TILs, the immunogenic potential of TNBC is derived from its genetic instability and high mutation rate. Tumors from patients with TNBC are more likely than tumors from patients with other subtypes to exhibit chromosomal instability and potential mutations. Objectives The study aims to evaluate the prevalence of CD8+ TILs biomarker by IHC in triple negative breast cancer and its prognostic value. TILs are an important prognostic value for the response of patient to chemotherapy the greater number of TILS is associated with higher probability of response to chemotherapy also decrease recurrence. TILS in triple negative breast cancer suggest a likely option for immunotherapy in this disease. Patients and Methods This is a retrospective study, which was carried on 30 female patients, Clinical data and paraffin wax block of female patients with triple negative breast cancer are to be collected from the breast cancer unit, department of clinical Oncology and Nuclear medicine Ain Shams university and Matarya teaching hospital. Results Several large systematic reviews and meta-analyses have confirmed that high levels of TILs are associated with better disease free survival and overall survival only in triple negative and HER2 positive subtypes, with no significant benefit seen in estrogen receptor positive breast carcinoma. In the Breast International Group (BIG) 02-98 trial shows that for every 10% increase in the intertumoral TILs there was a 17% reduced risk of relapse, and 27% reduced risk of death regardless of chemotherapy type. Also in eastern cooperative oncology group trial (ECOG) 2197, and 1199 showed that for every 10% increase in TILs, a 14% reduction of risk of recurrence, and 19% reduction in risk of death were observed. Conclusion Our study showed that All our patients (100%) were positive for CD8+, with a minimum range of 1% and a maximum range of 60%, most of the patients (20 patients) had CD8% between (10% to 20%). High levels of CD8 + TILs are good prognostic indicators in TNBC. our study showed that there were associations of CD8+ TILs infiltrate status with longer progression free survival and better overall survival in triple-negative breast cancer, but were not statistically significant probably due to our small sample size.


2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Ge Zhang ◽  
Wan-Li Liu ◽  
Lin Zhang ◽  
Jun-Ye Wang ◽  
Miao-Huan Kuang ◽  
...  

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.


Author(s):  
Toshiaki Iwase ◽  
Tushaar Vishal Shrimanker ◽  
Ruben Rodriguez-Bautista ◽  
Onur Sahin ◽  
Anjali James ◽  
...  

The purpose of this study was to determine the change in overall survival (OS) for patients with de novo metastatic breast cancer (dnMBC) over time. We conducted a retrospective cohort study with 1981 patients with dnMBC diagnosed between January 1995 and December 2017 at The University of Texas MD Anderson Cancer Center. OS was measured from the date of diagnosis of dnMBC. OS was compared between patients diagnosed during different time periods: 5-year periods and periods defined according to when key agents were approved for clinical use. The median OS was 3.4 years. The 5- and 10-year OS rates improved over time across both types of time periods. A subgroup analysis showed that OS improved significantly over time for the estrogen-receptor-positive/HER2-positive (ER+/HER2+) subtype, and exhibited a tendency toward improvement over time for the ER-negative (ER-)/HER2+ subtype. Median OS was significantly longer in patients with non-inflammatory breast cancer (P = .02) and in patients with ER+ disease, progesterone-receptor-positive disease, HER2+ disease, lower nuclear grade, locoregional therapy, and metastasis to a single organ (all P &amp;lt;.0001). These findings showed that OS at 5 and 10 years after diagnosis in patients with dnMBC improved over time. The significant improvements in OS over time for the ER+/HER2+ subtype and the tendency toward improvement for ER-/HER2+ subtype suggest the contribution of HER2-targeted therapy to survival.


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