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1.
Medicine (Baltimore) ; 100(51): e28109, 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34941052

RESUMO

ABSTRACT: To evaluate diagnostic performance of perfusion-weighted imaging in differentiating benign from malignant breast lesions, and the correlation between the prognostic factors/subtypes of breast cancers and the perfusion parameters.A total of 76 patients (59 cases with breast cancer) were included in our study. The Wilcoxon rank-sum test or the Kruskal-Wallis test were adopted for comparisons according to the dichotomous histopathologic prognostic factors or immunohistochemical subtypes. Receiver operating characteristic curves were used to determine the area under the curve (AUC) values for perfusion parameters to assess discrimination ability.Confirming by pathology after operation, the percentage of benign lesions is 22.37% (17/76), malignant lesions (breast cancer) is 77.63% (59/76). According to puncture and pathological findings after operation, the standard of the molecular subtypes of breast cancer, triple negative account for 13.6% (8/59), non-triple negative account for 86.4% (51/59). The value of mean Ktrans and Kep were lower in benign than malignant lesions (P ≤ .001). The AUC of the 3 indicators are significantly improved after adjusting for age (AUC = 0.858 for Ktrans, AUC = 0.926 for Kep, and AUC = 0.827 for Ve). Moreover, the Ve index showed better discrimination performance than other indicators in identifying patients with triple-negative subtypes. Similarly, the identification ability came to the highest when combing Kep and Ve.Perfusion parameters on dynamic enhanced magnetic resonance imaging are statistically significant in distinguishing benign from malignant breast lesion, and may potentially be used as biomarkers in discriminating patients with triple-negative molecular subtypes of breast cancer.

2.
Front Cell Dev Biol ; 9: 747314, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805157

RESUMO

Discoidin domain receptor tyrosine kinases (DDRs) are a class of receptor tyrosine kinases (RTKs), and their dysregulation is associated with multiple diseases (including cancer, chronic inflammatory conditions, and fibrosis). The DDR family members (DDR1a-e and DDR2) are widely expressed, with predominant expression of DDR1 in epithelial cells and DDR2 in mesenchymal cells. Structurally, DDRs consist of three regions (an extracellular ligand binding domain, a transmembrane domain, and an intracellular region containing a kinase domain), with their kinase activity induced by receptor-specific ligand binding. Collagen binding to DDRs stimulates DDR phosphorylation activating kinase activity, signaling to MAPK, integrin, TGF-ß, insulin receptor, and Notch signaling pathways. Abnormal DDR expression is detected in a range of solid tumors (including breast, ovarian, cervical liver, gastric, colorectal, lung, and brain). During tumorigenesis, abnormal activation of DDRs leads to invasion and metastasis, via dysregulation of cell adhesion, migration, proliferation, secretion of cytokines, and extracellular matrix remodeling. Differential expression or mutation of DDRs correlates with pathological classification, clinical characteristics, treatment response, and prognosis. Here, we discuss the discovery, structural characteristics, organizational distribution, and DDR-dependent signaling. Importantly, we highlight the key role of DDRs in the development and progression of breast and ovarian cancer.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34751400

RESUMO

BACKGROUND: Chimeric antigen receptor T cells (CAR-T) have been demonstrated remarkable efficacy in hematological cancers but have not yet translated in treating solid tumors. The significant hurdles limiting CAR-T therapy were due to a paucity of differentially expressed cell surface molecules on solid tumors that can be safely targeted. Here, we present thyroid-stimulating hormone receptor (TSHR) as a putative target for CAR-T therapy of differentiated thyroid cancer (DTC). METHODS: We undertook a large-scale screen on thyroid cancer tissues and multiple internal organs through bioinformatical analysis and immunohistochemistry to date TSHR expression. Using three previously described mAb, we generate three third-generation CAR-Ts. We tested anti-TSHR CAR-T in vitro activity by T-cell function and killing assay. Then we tested pre-clinical therapeutical efficacy in a xenograft mouse model of DTC and analyzed mice's physical conditions and histological abnormalities to evaluate anti-TSHR CAR-T's safety. RESULTS: TSHR is highly and homogeneously expressed on 90.8% (138/152) of papillary thyroid cancer, 89.2% (33/37) of follicular thyroid cancer, 78.2% (18/23) of the cervical lymph node metastases, and 86.7% of RAI-R diseases. We developed three novel anti-TSHR CAR-T from mAb M22, K1-18, and K1-70; all three CAR-Ts mediate significant anti-tumor activity in vitro. Among these, we demonstrate that K1-70 CAR-T can have therapeutical efficacy in vivo, and no apparent toxicity has been observed. CONCLUSION: TSHR is a latent target antigen of CAR-T therapy for DTC. Anti-TSHR CAR-T could represent a therapeutic option for patients with local-regional relapsed or distant metastases of thyroid cancer and should be tested in carefully designed clinical trials.

4.
Cancer Commun (Lond) ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34738326

RESUMO

BACKGROUND: To date, there is no approved blood-based biomarker for breast cancer detection. Herein, we aimed to assess semaphorin 4C (SEMA4C), a pivotal protein involved in breast cancer progression, as a serum diagnostic biomarker. METHODS: We included 6,213 consecutive inpatients from Tongji Hospital, Qilu Hospital, and Hubei Cancer Hospital. Training cohort and two validation cohorts were introduced for diagnostic exploration and validation. A pan-cancer cohort was used to independently explore the diagnostic potential of SEMA4C among solid tumors. Breast cancer patients who underwent mass excision prior to modified radical mastectomy were also analyzed. We hypothesized that increased pre-treatment serum SEMA4C levels, measured using optimized in-house enzyme-linked immunosorbent assay kits, could detect breast cancer. The endpoints were diagnostic performance, including area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Post-surgery pathological diagnosis was the reference standard and breast cancer staging followed the TNM classification. There was no restriction on disease stage for eligibilities. RESULTS: We included 2667 inpatients with breast lesions, 2378 patients with other solid tumors, and 1168 healthy participants. Specifically, 118 patients with breast cancer were diagnosed with stage 0 (5.71%), 620 with stage I (30.00%), 966 with stage II (46.73%), 217 with stage III (10.50%), and 8 with stage IV (0.39%). Patients with breast cancer had significantly higher serum SEMA4C levels than benign breast tumor patients and normal controls (P < 0.001). Elevated serum SEMA4C levels had AUC of 0.920 (95% confidence interval [CI]: 0.900-0.941) and 0.932 (95%CI: 0.911-0.953) for breast cancer detection in the two validation cohorts. The AUCs for detecting early-stage breast cancer (n = 366) and ductal carcinoma in situ (n = 85) were 0.931 (95%CI: 0.916-0.946) and 0.879 (95%CI: 0.832-0.925), respectively. Serum SEMA4C levels significantly decreased after surgery, and the reduction was more striking after modified radical mastectomy, compared with mass excision (P < 0.001). The positive rate of enhanced serum SEMA4C levels was 84.77% for breast cancer and below 20.75% for the other 14 solid tumors. CONCLUSIONS: Serum SEMA4C demonstrated promising potential as a candidate biomarker for breast cancer diagnosis. However, validation in prospective settings and by other study groups is warranted.

5.
BMC Endocr Disord ; 21(1): 208, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34670546

RESUMO

BACKGROUND: To assess the gaps between the initial management of patients with differentiated thyroid cancer (DTC) in real clinical practice and the recommendations of the 2012 Chinese DTC guidelines. METHODS: This multicenter, prospective study was conducted at nine tertiary hospitals across China. Eligible patients were those having intermediate or high-risk DTC after first-time thyroidectomy. During 1 year of follow-up, comprehensive medical records were collected and summarized using descriptive statistics. RESULTS: Of 2013 patients, 1874 (93.1%) underwent standard surgery according to the guidelines (including total lobectomy plus isthmusectomy and total/near total thyroidectomy), and 1993 (99.0%) underwent lymph node dissection; only 56 (2.8%) had postoperative complications. Overall, 982/2013 patients (48.8%) received radioactive iodine (RAI) therapy after thyroidectomy. Of all enrolled patients, 61.4% achieved the target serum thyroid-stimulating hormone level, with a median time to target of 234.0 days (95% CI: 222.0-252.0). At 1 year of follow-up, proportions of patients with excellent response, incomplete structural response, biochemical incomplete response, and indeterminate response were 34.6, 11.2, 6.6, and 47.5%, respectively; recurrence or metastasis occurred in 27 patients (1.3%). During the overall study period, 209 patients (10.4%) had at least one adverse event: 65.1% of cases were mild, 24.9% moderate, and 10.1% severe. CONCLUSIONS: This was the first large-scale prospective study of how patients with DTC in China are treated in actual practice. Initial DTC management is generally safe and adheres to the 2012 Chinese guidelines but could be improved, and the level of guideline adherence did not produce the anticipated treatment response at 1 year of follow-up.

6.
Pathol Oncol Res ; 27: 1609811, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712105

RESUMO

Background: The preoperative systemic inflammation response index (SIRI), based on peripheral neutrophil (N), monocyte (M), and lymphocyte (L) counts, has shown mounting evidence as an effective prognostic indicator in some malignant tumors. The aim of the present study was to evaluate the prognostic significance of pre-treatment SIRI in gastric cancer patients who received neoadjuvant chemotherapy (NACT). Methods: This retrospective study comprised 107 patients with advanced gastric cancer treated with NACT between July 2007 and September 2015 in our hospital. SIRI was calculated from peripheral venous blood samples obtained prior to treatment. The best cutoff value for SIRI by receiver operating characteristic (ROC) curve was 1.2 (low SIRI <1.21, high SIRI ≥1.21). The clinical outcomes of disease-free survival (DFS) and overall survival (OS) were analyzed by Kaplan-Meier survival analysis and compared using the log-rank test. Univariate and multivariate analyses were performed by the Cox proportional hazards regression model. Results: The results demonstrated that the low SIRI group was statistically associated with gender, primary tumor site, white blood cell, neutrophil, and monocyte counts, NLR (neutrophil to lymphocyte ratio), MLR (monocyte to lymphocyte ratio), and PLR (platelet to lymphocyte ratio). The SIRI was predictive for DFS and OS by univariate and multivariate analysis; the low SIRI group had better median DFS and OS than the high SIRI group (median DFS 27.03 vs. 22.33 months, median OS 29.73 vs. 24.43 months). The DFS and OS in the low SIRI group were longer than the high SIRI group. Conclusions: SIRI may qualify as a useful, reliable, and convenient prognostic indicator in patients with advanced gastric cancer to help physicians to provide personalized prognostication for gastric cancer patients treated with NACT.

7.
Ear Nose Throat J ; : 1455613211039807, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34472380

RESUMO

PURPOSE: To evaluate the impact of parathyroid gland vasculature preservation in-situ technique (PGVPIST) on postoperative parathyroid hormone (PTH) and calcium plasma levels in thyroid patients undergoing total thyroidectomy for papillary thyroid carcinoma (PTC). STUDY DESIGN: Retrospective cohort study. METHODS: Patients with PTC who underwent total thyroidectomy by either the conventional technique (group 1, January 2019 to January 2020) or PGVPIST (group 2, January 2020 to January 2021) were compared. Postoperative blood calcium levels and PTH levels were assessed in these groups. RESULTS: Totally 149 patients with consecutive PTC underwent total thyroidectomy, including 60 patients in group 1 and 89 patients in group 2. Postoperative serum calcium levels in group 1 were insignificantly lower than in group 2 at day 1 (2.18 ± 0.02 vs 2.15 ± 0.01 mmol/L) and day 30 (2.27 ± 0.02 vs 2.38 ± 0.11) after surgery. But postoperative serum PTH levels in group 1 were significantly lower than that in group 2 at day 1 (23.68 ± 2.54 vs 31.46 ± 2.11 pg/mL) and day 30 (45.63 ± 3.21 vs 55.65 ± 2.89 pg/mL) after surgery. CONCLUSION: Parathyroid gland vasculature preservation in-situ technique for PTC is associated with higher PTH level after total thyroidectomy. The parathyroid gland vasculature mostly strongly adheres with adjacent thyroid parenchyma. Therefore, deferred processing of tiny thyroid parenchyma of parathyroid gland vessels is essential to prevent devascularization.

8.
J Cancer ; 12(19): 5760-5771, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34475990

RESUMO

S100 calcium binding protein A1 (S100A1) is an important member of the S100 family and known to express in a variety of cancers. However, the biological functions of S100A1 in thyroid carcinoma have not been thoroughly studied. In this report, bioinformatics analyses and immunohistochemistry assays were applied to assess the expression profile of S100A1 as well as its relationship with the pathological features and prognosis of papillary thyroid carcinoma (PTC). Meanwhile, functions of S100A1 in PTC cells were analyzed with either in vitro or in vivo experiments. S100A1 was significantly up-regulated in PTC tissues compared with adjacent non-cancerous tissues. S100A1 protein expression was significantly associated with tumor size (p=0.0032) or lymph node metastasis (p=0.0331). More importantly, an elevated S100A1 expression was significantly correlated with a worse recurrence-free survival (RFS) (HR=2.26, p=0.042). Further, knockdown of S100A1 dramatically inhibited cell proliferation and migration as well as increased apoptosis of PTC cells. S100A1 knockdown inhibited tumor progression as seen in in vivo experiments. In terms of mechanism, down-regulation of S100A1 induced yes associated protein (YAP) phosphorylation in the cytoplasm and diminished Hippo/YAP pathway activation. Therefore, S100A1 may serve as a novel oncogene and a promising biomarker for PTC diagnosis and prognosis.

10.
Ann Med ; 53(1): 916-928, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34134578

RESUMO

BACKGROUND: The overall response rate of immunotherapy in triple-negative breast cancer (TNBC) remains unsatisfactory. Accumulating evidence indicated that glucose metabolic reprogramming could modulate immunotherapy efficacy. However, transcriptomic evidence remains insufficient. METHODS: Genes' relationship with glucose metabolism and TNBC-specific immune was demonstrated by weighted gene co-expression network analysis (WGCNA). The glucose metabolic capability was estimated by standardised uptake value (SUV), an indicator of glucose uptake in 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET), and a reflection of cancer metabolic behaviour. PD-(L)1 expression was used to reflect the efficacy of immunotherapy. Additionally, immune infiltration, survival, and gene coexpression profiles were provided. RESULTS: Comprehensive analysis revealing that IL4I1, ITGB7, and FUT7 hold the potential to reinforce immunotherapy by reshaping glucose metabolism in TNBC. These results were verified by functional enrichment analysis, which demonstrated their relationships with immune-related signalling pathways and extracellular microenvironment reprogramming. Their expressions have potent positive correlations with Treg and Macrophage cell infiltration and exhausted T cell markers. Meanwhile, their overexpression also lead to poor prognosis. CONCLUSION: IL4I1, ITGB7, and FUT7 may be the hub genes that link glucose metabolism, and cancer-specific immunity. They may be potential targets for enhancing ICB treatment by reprogramming the tumour microenvironment and remodelling tumour metabolism.


Assuntos
Fluordesoxiglucose F18 , Fucosiltransferases , Cadeias beta de Integrinas , L-Aminoácido Oxidase , Neoplasias de Mama Triplo Negativas , Fucosiltransferases/genética , Glucose/metabolismo , Glicólise , Humanos , Cadeias beta de Integrinas/genética , L-Aminoácido Oxidase/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/terapia , Microambiente Tumoral
11.
Oncol Lett ; 21(4): 323, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33692855

RESUMO

The role of non-SMC condensin I complex subunit G (NCAPG) in breast cancer remains unclear. The present study used online databases, reverse transcription-quantitative PCR, flow cytometry and western blotting to determine the expression levels, prognosis and potential molecular mechanisms underlying the role of NCAPG in breast cancer. The association between NCAPG expression and several different clinicopathological parameters in patients with breast cancer was determined, and the results revealed that NCAPG expression was negatively associated with estrogen receptor and progesterone receptor positive status, but was positively associated with HER2 positive status, Nottingham Prognostic Index score and Scarff-Bloom-Richardson grade status. Furthermore, upregulated expression levels of NCAPG resulted in a poor prognosis in patients with breast cancer. A total of 27 microRNAs (miRNAs/miRs) were predicted to target NCAPG, among which four miRNAs (miR-101-3p, miR-195-5p, miR-214-3p and miR-944) were predicted to most likely regulate NCAPG expression in breast cancer. A total of 261 co-expressed genes of NCAPG were identified, including cell division cyclin 25 homolog C (CDC25C), and pathway enrichment analysis indicated that these co-expressed genes were significantly enriched in the p53 signaling pathway. CDC25C expression was downregulated in breast cancer and was associated with a poor prognosis. These findings suggested that upregulated NCAPG expression may be a prognostic biomarker of breast cancer.

12.
Oncol Lett ; 21(5): 368, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33777194

RESUMO

Long non-coding RNAs (lncRNAs) may participate in biological regulatory mechanisms of tumors. The aim of the present study was to uncover the molecular mechanism of the lncRNA LINC00052 in the tumorigenesis of breast cancer (BC). LINC00052 expression in BC tissues and cell lines was detected by reverse transcription-quantitative PCR analysis. The Cell Counting Kit-8, proliferation, Transwell and wound healing assays were employed to confirm the effect of LINC00052 on cell proliferation, migration and invasion. The cell localization of LINC00052 was estimated by cytoplasmic nuclear separation assay. Finally, the potential regulatory mechanism of LINC00052 in BC was detected by western blot analysis. The expression levels of LINC00052 were found to be significantly higher in BC tissues compared with those in the adjacent normal tissues. Downregulation of LINC00052 expression in vitro significantly suppressed the proliferation, migration and invasion of BC cells. LINC00052 was mainly expressed in the cytoplasm and was considered to bind with microRNA (miR)-145-5p based on various databases. Notably, the high expression levels of LINC00052 led to the low expression levels of miR-145-5p and high expression levels of TGF-ß receptor II (TGFBR2). In conclusion, the findings of the present study demonstrated that LINC00052 may sponge miR-145-5p to upregulate TGFBR2 expression in order to promote the proliferation and metastasis of BC cells. Therefore, LINC00052 may be an effective potential target for the diagnosis and treatment of BC.

13.
Front Cell Dev Biol ; 9: 647736, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777954

RESUMO

As one of the most frequently occurring malignancies in women, breast cancer (BC) is still an enormous threat to women all over the world. The high mortality rates in BC patients are associated with BC recurrence, metastatic progression to distant organs, and therapeutic resistance. Circular RNAs (circRNAs), belonging to the non-coding RNAs (ncRNAs), are connected end to end to form covalently closed single-chain circular molecules. CircRNAs are widely found in different species and a variety of human cells, with the features of diversity, evolutionary conservation, stability, and specificity. CircRNAs are emerging important participators in multiple diseases, including cardiovascular disease, inflammation, and cancer. Recent studies have shown that circRNAs are involved in BC progress by regulating gene expression at the transcriptional or post-transcriptional level via binding to miRNAs then inhibiting their function, suggesting that circRNAs may be potential targets for early diagnosis, treatment, and prognosis of BC. Herein, in this article, we have reviewed and summarized the current studies about the biogenesis, features, and functions of circRNAs. More importantly, we emphatically elucidate the pivotal functions and mechanisms of circRNAs in BC growth, metastasis, diagnosis, and drug resistance. Deciphering the complex networks, especially the circRNA-miRNA target gene axis, will endow huge potentials in developing therapeutic strategies for combating BC.

14.
Nat Commun ; 11(1): 5793, 2020 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-33188186

RESUMO

Magnetic resonance (MR) technology has been widely employed in scientific research, clinical diagnosis and geological survey. However, the fabrication of MR radio frequency probeheads still face difficulties in integration, customization and miniaturization. Here, we utilized 3D printing and liquid metal filling techniques to fabricate integrative radio frequency probeheads for MR experiments. The 3D-printed probehead with micrometer precision generally consists of liquid metal coils, customized sample chambers and radio frequency circuit interfaces. We screened different 3D printing materials and optimized the liquid metals by incorporating metal microparticles. The 3D-printed probeheads are capable of performing both routine and nonconventional MR experiments, including in situ electrochemical analysis, in situ reaction monitoring with continues-flow paramagnetic particles and ions separation, and small-sample MR imaging. Due to the flexibility and accuracy of 3D printing techniques, we can accurately obtain complicated coil geometries at the micrometer scale, shortening the fabrication timescale and extending the application scenarios.

15.
Cancer Cell Int ; 20: 501, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061853

RESUMO

Background: Triple-negative breast cancer (TNBC) is a highly aggressive malignancy that lacks sensitivity to chemotherapy, endocrine therapy or targeted therapy. CDK4/6 inhibitors, combined with endocrine therapy, have been shown to be effective in postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer. Therefore, we investigated whether the CDK4/6 inhibitor palbociclib (PD) could enhance the effects of cisplatin (CDDP) on TNBC. Methods: The effects of different drug regimens consisting of PD and CDDP on MDA-MB-231 and RB-knockdown MDA-MB-231 (sh-MDA-MB-231) cells were assessed in vitro and in vivo. MDA-MB-468 and RB-overexpressing MDA-MB-468 cells were used to assess the effect of the PD-CDDP regimens in vitro. Immunoblotting illustrated the role of the cyclin D1/RB/E2F axis signalling pathway. Results: PD induced G1 phase cell cycle arrest in the MDA-MB-231 cell line. However, synchronous treatment with PD and CDDP for 24 h, treatment with PD for 24 h followed by CDDP and treatment with CDDP for 24 h followed by PD had no influence on MDA-MB-231 cell apoptosis. We further investigated the effect of PD or CDDP withdrawal on the effects of sequential treatment and found that PD treatment for 48 h followed by withdrawal for 48 h and subsequent CDDP treatment (PD-CDDP) significantly increased apoptosis and inhibited the cell viability and colony formation of MDA-MB-231 cells, while with other regimens, PD and CDDP had an additive or antagonistic response. The preferential use of PD increased DNA damage induced by CDDP, as measured through γH2AX immunofluorescence. These findings were not observed in sh-MDA-MB-231 cells, and experiments to assess cell function in MDA-MB-468 and RB-overexpressing MDA-MB-468 cells yielded similar results, which indicated that PD enhanced the sensitivity of TNBC cells to CDDP in an RB-dependent manner. In vivo, compared with single drug treatment, combination treatment inhibited tumour growth and Ki-67 expression in MDA-MB-231 xenograft models. Western blot analysis revealed that PD enhanced sensitivity to CDDP through the CDK4/6-cyclin D1-RB-E2F pathway. Conclusions: Pre-treatment with PD synchronized the tumour cell cycle through the CDK4/6-cyclin D1-RB-E2F pathway, which increased the antitumour effect of CDDP. Thus, PD-CDDP might be an effective treatment for RB-proficient TNBC patients.

16.
Cancer Med ; 9(24): 9554-9570, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33058542

RESUMO

Breast cancer (BC) poses one of the major threats to female's health worldwide. Immune infiltration in BC is a key representative of the tumor microenvironment and has been proven highly relevant for prognosis. The role of the FREM1 (FRAS1-Related Extracellular Matrix 1) gene in carcinoma has not studied, moreover, the underlying mechanism remains largely unknown. This study aims to investigate the expression profile and potential action of FREM1 on BC progression. We applied series of bioinformatic methods as well as immunohistochemistry (IHC) and immunofluorescence (IF) to analyze FREM1 expression profile, its relationship with clinicopathological characteristics, impact on clinical outcomes, relevant functions, correlation with immune infiltration in BC. The results demonstrated that FREM1 had a dramatically reduced expression in BC tissues, possessed an inverse correlation with stage, age, and metastasis, and exhibited a higher level in invasive lobular breast carcinoma than in ductal one. Furthermore, decreased FREM1 expression was often associated with estrogen receptor (ER)/progesterone receptor (PR) negative and triple negative breast carcinoma (TNBC) status while human epidermal growth factor 2 (Her-2) positive status, and considerably correlated with a worse overall survival (OS) and recurrence-free survival (RFS). Meanwhile, the univariate/multivariate Cox model revealed that low-FREM1 expression can be an independent prognostic factor for BC. Additionally, FREM1 was mainly involved in the cell metabolism and immune cells infiltration. Moreover, IHC and IF demonstrated a positive correlation of its expression with the immune infiltrating levels of CD4+ , CD8+ T cells, and CD86+ M1 macrophages while a negative correlation with CD68+ pan-macrophages and CD163+ M2 macrophages. These findings suggest that FREM1 can be a potential biomarker for evaluating the immune infiltrating status, and the BC prognosis.


Assuntos
Neoplasias da Mama/imunologia , Linfócitos do Interstício Tumoral/imunologia , Receptores de Interleucina/imunologia , Receptores de Progesterona/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Biologia Computacional/métodos , Bases de Dados Genéticas , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Receptor ErbB-2/metabolismo , Receptores de Interleucina/biossíntese , Receptores de Interleucina/genética , Receptores de Interleucina/metabolismo , Taxa de Sobrevida
17.
EClinicalMedicine ; 26: 100503, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32989430

RESUMO

Background: Cancer patients had been profoundly affected by the outbreak of COVID-19 especially after quarantine restrictions in China. We aimed to explore the treatment changes and delays of early breast cancer (EBC) during the first quarter of 2020. Methods: We did this retrospective, multicentre, cohort study at 97 cancer centres in China. EBC patients who received treatment regardless of preoperative therapy, surgery or postoperative therapy during first quarter of 2020 were included. Findings: 8397 patients were eligible with a median age of 50 (IQR 43-56). 0·2% (15/8397) of EBC patients were confirmed as COVID-19 infection. Only 5·2% of breast cancer diagnosis occurred after quarantine in Hubei compared with 15·3% in other provinces (OR= 0·30, 95%CI 0·24-0·38). postoperative endocrine therapy were least affected compared with different regions after quarantine (OR=0·37 [95%CI 0·19-0·73]). The proportion of surgery decreased from 16·4% in December last year to 2·6% in February in Hubei. Compared with intervals from diagnosis to treatment before quarantine restrictions, the average time increased with significance from 3·5 to 7·7 days in Hubei and 5·7 to 7·7 days in other provinces (p< 0·001). There were also 18·5 and 7·2 days delay in Hubei and other provinces respectively when calculating interval from surgery to postoperative therapy. Interpretation: EBC from high risk regions had a comparative rate of COVID-19 infection. After implementation of COVID-19 quarantine restrictions, fewer diagnosis and surgery with significant delays were seen when compared with treatment before. Funding: Beijing Medical Award Foundation (YJ0120).

18.
Aging (Albany NY) ; 12(17): 17305-17327, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32915772

RESUMO

Immune checkpoint inhibition has emerged as an effective treatment for multiple solid tumors, including advanced-stage breast cancer (BC). During the past decade, the US Food and Drug Administration has approved a number of agents for immune checkpoint blockade (ICB). However, the limited data on monotherapy anti-tumor activity in BC underscores the need for robust predictive biomarker development. Here, we used weighted gene coexpression network analysis of genes differentially expressed between BC and normal tissue to identify genes coexpressed with programmed death-1 (PD-1) and its ligand (PD-L1). Tumor Immune Estimation Resource and Gene Expression Profiling Interaction Analysis were used to assess the relationship between gene expression and the abundance of tumor-infiltrating lymphocytes (TILs). We found that chloride intracellular channel protein 2 (CLIC2) was not only coexpressed with PD-1 and PD-L1, but its increased expression was associated with a favorable prognosis and enrichment of multiple TIL types, particularly CD8+ T cells. These results suggest that CLIC2 is a potentially useful biomarker for identifying BC patients who could benefit from ICB.

19.
Lab Chip ; 20(19): 3625-3632, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-32901644

RESUMO

The enzyme-linked immunosorbent assay (ELISA) is one of the most commonly implemented clinical diagnostic tools for the detection and quantification of protein biomarkers. However, conventional ELISA tests require sophisticated infrastructure, expensive reagents, long assay time, and expertise for operation, which are not often easily accessible in resource-limited settings. Microfluidic ELISA-chip based point-of-care (POC) testing allows miniaturization and integration of complex functions that facilitate their usage in limited-resource settings. The current work demonstrates a simple, portable, low cost and equipment-free paper/poly(methyl methacrylate) (PMMA) integrated microfluidic ELISA-chip as a POC device with a visual distance-based readout for quantitative detection of clinical biomarkers. The integrated paper/PMMA ELISA-chip utilizes the movement of immunoassay complexes with magnetic beads by a permanent magnet in a PMMA part of the compartment. The target concentration is translated into a visual distance signal readout for quantitative detection of biomarkers in a µPAD. Because it does not require sophisticated instruments and has the added advantages of low cost, easy operation, and disposability with quantitative visual readout, the paper/PMMA ELISA-chip holds great promise for portable detection of target bioanalytes as a POC diagnostic tool in resource-limited setups.


Assuntos
Técnicas Analíticas Microfluídicas , Polimetil Metacrilato , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G , Microfluídica , Testes Imediatos
20.
Cancer Manag Res ; 12: 5773-5786, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765080

RESUMO

Background: Ovarian cancer is a major gynecologic malignancy that is often detected at a late stage due to the lack of detailed studies on its pathogenesis and reliable biomarkers for predicting its prognosis. Materials and Methods: Four ovarian cancer data sets GSE18520, GSE27651, GSE40595, and GSE52037 were downloaded from the Gene Expression Omnibus (GEO) database and the robust rank aggregation approach was used to find common differentially expressed genes (DEGs). Cytoscape software was used to construct and detect key models of protein-protein interaction (PPI) network. While the expression, prognostic value and potential mechanism of the hub gene non-SMC condensin I complex subunit G (NCAPG) was carried out through Gene Expression Profiling Interactive Analysis, Kaplan-Meier plotter online dataset and gene set enrichment analysis. To further investigate the role of NCAPG in ovarian cancer, in vitro experiments were carried out. Results: A total of 232 DEGs were identified in the four GEO datasets; and we detected 32 hub genes from the PPI network and 21 of these genes were associated with ovarian cancer prognosis, one of which was NCAPG. NCAPG was significantly upregulated in most of the ovarian cancer samples. High NCAPG expression was mainly involved in homologous recombination, DNA replication, proteasome, and more correlated pathways. NCAPG knockdown arrested the cell cycle, inhibited the proliferation, and attenuated the migration ability of A2780 cells. Meanwhile, silencing of NCAPG significantly promoted cisplatin-induced apoptosis thus increased the sensitivity to cisplatin. Conclusion: NCAPG together with the other 31 hub genes play a vital role in the tumorigenesis of ovarian, meanwhile, the cell cycle pathway may be a potential pathway contributing to progression in OC; and NCAPG expression can be used as a promising target for the treatment of OC.

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