LncRNA MIR205HG expression predicts efficacy of neoadjuvant chemotherapy for patients with locally advanced breast cancer.
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ABSTRACT:
SUBMITTER: Xu Y
PROVIDER: S-EPMC9170602 | biostudies-literature | 2022 Jul
REPOSITORIES: biostudies-literature
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LncRNA MIR205HG expression predicts efficacy of neoadjuvant chemotherapy for patients with locally advanced breast cancer.
Xu Yaqian Y Yuan Chenwei C Peng Jing J Zhou Liheng L Lin Yanping Y Wang Yaohui Y Zhang Jie J Ma Jiayi J Yin Wenjin W Lu Jinsong J
Genes & diseases 20211101 4
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Project description:Endothelin-1 (ET-1) and its receptors (ETAR and ETBR), referred to as the endothelin (ET) axis, are overexpressed in breast carcinomas and appear to influence tumour growth and progression. The objective of this study was to determine the effect of expression of the ET axis in breast carcinomas on response to cytotoxic chemotherapy. The study included 44 patients with locally advanced breast cancer participating in a prospective phase III study evaluating high-dose neoadjuvant chemotherapy of epirubicin and cyclophosphamide. Expression of ET-1, ETAR and ETBR was determined by semiquantitative immunohistochemical analysis of breast cancer tissue from prechemotherapy tru-cut biopsies. Immunohistochemical staining was positive for ET-1 in 61.5%, for ETAR in 35% and for ETBR in 35.9% of breast carcinomas. Pathological response to chemotherapy was significantly decreased in ETAR-positive patients (P=0.002). In total, 50% of ETAR-positive patients as compared to 7.7% of ETAR-negative patients attained pathologically 'no change'. Logistic regression confirmed ETAR as an independent predictive marker for pathological response (P=0.009). These data indicate that increased expression of ETAR in breast carcinomas is associated with resistance to chemotherapy. Determination of ETAR status may serve as a predictive marker for identifying patients less likely to be responsive to conventional chemotherapy.
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Project description:AimThe aim of the present study was to explore the association between CD133 expression and postoperative relapses in patients with locally advanced rectal cancer (LARC) who received neoadjuvant chemotherapy (NAC).Patients and methodsWe retrospectively examined 52 patients with LARC (cT3-4, Nany, M0) who received oxaliplatin-based NAC before surgery. CD133 expression was evaluated using immunohistochemistry and divided into low and high expression groups.ResultsHigh CD133 expression was observed in 22 patients (42.3%). Patients with high CD133 expression had more frequent vessel invasion and relapse than those with low CD133 expression (p=0.013 and p=0.036, respectively). Comparing the low with high CD133 expression groups, the 4-year relapse-free survival rates were 82.2% vs. 46.3% (p=0.009). Multivariate analysis indicated that CD133 expression was an independent risk factor for relapse (HR=3.138; 95%CI=1.046-9.412; p=0.041).ConclusionCD133 expression may be a predictive biomarker for postoperative relapse in patients with LARC who received NAC before surgery.
| S-EPMC7880757 | biostudies-literature
Project description:BackgroundSerum tumor markers including AFU, AFP, CEA, CA199, CA125 and CA724, are of great importance in the diagnosis, prognostic prediction and recurrence monitoring of gastrointestinal malignancies. However, their significance in gastric cancer (GC) patients with neoadjuvant therapy (NCT) is still uncertain. The aim of this study was to evaluate the predictive value of these six tumor markers in locally advanced GC patients who underwent NCT and curative surgery.MethodsIn total, 290 locally advanced GC patients who underwent NCT and D2 radical gastrectomy were retrospectively analyzed. Data on their tumor markers before (pre-) and after (post-) NCT and pathological characteristics were extracted from the database of our hospital. The optimal cutoff values of the six tumor markers were calculated by the ROC curve and Youden index. Their predictive significance was analyzed and survival curves for overall survival (OS) were obtained by the Kaplan-Meier method. Associations between categorical variables were explored by the chi-square test or Fisher's exact test. Multivariate analyses were performed by the Cox regression model.ResultsPre- and post-CA199, -CA125 and -CA724 could predict overall survival (all P < 0.05), but only the change (diff-) of CA199 was related to prognosis (P = 0.05). In the multivariable analysis, pre- (P = 0.014) and post-CA724 (P = 0.036) remained significant, though diff-CA724 was not an independent prognostic factor (P = 0.581). In addition, pre- and post-CA199, -CA125 and -CA724 were associated with lymph node metastasis (N- vs N+) and pathological stage (I-II vs III) (all P < 0.05). Moreover, post-CA724 was related to the vascular or lymphatic invasion (P = 0.019), while pre-CA724 was not (P = 0.082). However, AFU, AFP and CEA showed no association with survival (P > 0.05).ConclusionsCA724 is an independent factor for prognosis and could be used to predict ypN and ypTNM stage in locally advanced GC patients undergoing NCT and curative resection.
| S-EPMC7786973 | biostudies-literature
Project description:Purpose: Tumor regression grade (TRG) is widely used to evaluate the efficacy of neoadjuvant chemotherapy (NCT) and it is related to many clinicopathological factors. However, whether TRG can be predicted by clinical characteristics is unknown. Methods: 141 locally advanced gastric cancer (GC) patients who underwent NCT and curative operation were retrospectively analyzed. TRG is reevaluated according to the CAP guideline. The values of CA199, CA125 and CA724 before NCT (pre-) and after NCT (post-) were extracted from our database. Survival curves on overall survival (OS) were obtained by Kaplan-Meier method, and differences were analyzed by log-rank test. Associations between categorical variables were explored by chi-square test or Fisher's exact method. Univariable and multivariate analyses were performed by logistic regression model or Cox proportional hazard regression model. Results: TRG was related to OS (P < 0.001), especially when divided into responders (TRG 0-1) and non-responders (TRG 2-3). Pre-CA724 (p = 0.029) and post-CA199 (p = 0.038) were related to OS. In multivariable analysis, pre-CA724 (p = 0.015) and post-CA199 (p = 0.007) were independent prognostic factors for OS, respectively. The changes (diff-) of all tumor markers were not related to OS. Among the clinical characteristics, pre-CA724 (P = 0.047) and tumor size (P = 0.012) were related to TRG, while pre-CA199 (P = 0.377) and pre-CA125 (P = 0.856) were not. In logistics analysis, pre-CA724 (P = 0.032), tumor size (P = 0.011) and tumor location (P = 0.047) were independent risk factors to pathological response. Conclusion: CA724 was an independent prognostic factor for OS and could be used to predict pathological response.
| S-EPMC8489128 | biostudies-literature
Project description:To elucidate candidate genes and pathways associated with poor response, we retrospectively analyzed gene expression profiles in serial biopsies from women with locally advanced breast cancer who failed to respond to anthracycline-based chemo followed by taxane in the I-SPY Of the 221 patients who completed neoadjuvant chemotherapy, 215 patients had surgery with 73% not achieving a pathologic complete response (pathCR). In these patients, cDNA microarray expression profiles from pretreatment biopsy (T1) were compared to those biopsy specimens obtained 24-72 hours after initiation of treatment (T2) or in tumors surgically removed after chemotherapy (TS). Paired expression data for T1vsT2 and T1vsTS were available for 29 and 39 patients with no pathCR, respectively. Paired differential expression analyses were performed via Significance Analysis of Microarrays (SAM) and differentially expressed genes were subjected to Ingenuity Pathway Analysis
2015-06-12 | E-GEOD-32603 | biostudies-arrayexpress
Project description:Background. There is evidence that the stromal compartment may influence breast cancer responsiveness to chemotherapy. Our aim was to detect a stromal cell signature (using a direct approach of microdissected stromal cells) associated with response to neoadjuvant chemotherapy in locally advanced breast cancer, considering tumor down staging (to at least ypT1a/b,ypN0), as the best response. Patients and methods. Forty four patients diagnosed with locally advanced breast cancer (29 classified as estrogen receptor (ER) positive and 15, as ER negative) were included. Neoadjuvant chemotherapy consisted of doxorubicin/cyclophosphamide, followed by paclitaxel. Response was defined as downstaging to maximum ypT1a-b/ypN0. Stromal cells were microdissected from fresh frozen tumor samples and gene expression profile was determined using Agilent SurePrint G3 Human Gene Expression Microarrays. Expression levels were compared using MeV (MultiExperiment Viewer) software, applying SAM (Significance analysis of microarrays). Gene set enrichment analysis was used to identify gene sets correlated with the phenotype downstaging. Results: After chemotherapy, nine patients presented disease downstaging to maximum ypT1a-b/ypN0. Using SAM test (FDR 17), 11 sequences were differentially expressed, all of which (except for H2AFJ) more expressed in responsive tumors. Gene list enrichment analysis revealed three genes involved in abnormal cytotoxic T cell physiology: TOX, LY75 and SH2D1A. Gene sets correlated with tumor downstaging (FDR < 0.01), were mainly involved in immune response or lymphocyte activation, both in ER positive and ER negative samples. Conclusion: In locally advanced breast cancer, stromal cells may present specific features of immune response that may be associated with chemotherapy response.
2020-01-18 | GSE143846 | GEO
Project description:Purpose To characterize intratumoral spatial heterogeneity at perfusion magnetic resonance (MR) imaging and investigate intratumoral heterogeneity as a predictor of recurrence-free survival (RFS) in breast cancer. Materials and Methods In this retrospective study, a discovery cohort (n = 60) and a multicenter validation cohort (n = 186) were analyzed. Each tumor was divided into multiple spatially segregated, phenotypically consistent subregions on the basis of perfusion MR imaging parameters. The authors first defined a multiregional spatial interaction (MSI) matrix and then, based on this matrix, calculated 22 image features. A network strategy was used to integrate all image features and classify patients into different risk groups. The prognostic value of imaging-based stratification was evaluated in relation to clinical-pathologic factors with multivariable Cox regression. Results Three intratumoral subregions with high, intermediate, and low MR perfusion were identified and showed high consistency between the two cohorts. Patients in both cohorts were stratified according to network analysis of multiregional image features regarding RFS (log-rank test, P = .002 for both). Aggressive tumors were associated with a larger volume of the poorly perfused subregion as well as interaction between poorly and moderately perfused subregions and surrounding parenchyma. At multivariable analysis, the proposed MSI-based marker was independently associated with RFS (hazard ratio: 3.42; 95% confidence interval: 1.55, 7.57; P = .002) adjusting for age, estrogen receptor (ER) status, progesterone receptor status, human epidermal growth factor receptor type 2 (HER2) status, tumor volume, and pathologic complete response (pCR). Furthermore, imaging helped stratify patients for RFS within the ER-positive and HER2-positive subgroups (log-rank test, P = .007 and .004) and among patients without pCR after neoadjuvant chemotherapy (log-rank test, P = .003). Conclusion Breast cancer consists of multiple spatially distinct subregions. Imaging heterogeneity is an independent prognostic factor beyond traditional risk predictors.
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Project description:PurposeNeoadjuvant chemotherapy (NCT) is a standard treatment option for locally advanced breast cancer. However, the lack of an efficient method to predict treatment response and patient prognosis hampers the clinical evaluation of patient eligibility for NCT. An elevated lymphocyte-to-monocyte ratio (LMR) has been reported to be associated with a favorable prognosis for certain hematologic malignancies and for nasopharyngeal carcinoma; however, this association has not been investigated in breast cancer. The purpose of this study was to evaluate whether pre-NCT LMR analysis could predict the prognosis of patients with locally advanced breast cancer.MethodsA retrospective cohort of 542 locally advanced breast cancer patients (T3/T4 and/or N2/N3 disease) receiving NCT followed by radical surgery was recruited between May 2002 and August 2011 at the Fudan University Shanghai Cancer Center. Counts for pre-NCT peripheral absolute lymphocytes and monocytes were obtained and used to calculate the LMR.ResultsUnivariate and multivariate analysis revealed that higher LMR levels (≥4.25) were significantly associated with favorable DFS (P = 0.009 and P = 0.011, respectively). Additionally, univariate analysis revealed that a higher lymphocyte count (≥1.5×109/L) showed borderline significance for improved DFS (P = 0.054), while a lower monocyte count (<0.4×109/L) was associated with a significantly better DFS (P = 0.010).ConclusionsAn elevated pre-NCT peripheral LMR level was a significantly favorable factor for locally advanced breast cancer patient prognosis. This easily obtained variable may serve as a valuable marker to predict the outcomes of locally advanced breast cancer.
| S-EPMC4221197 | biostudies-literature
Project description:Backgroundthis study aimed to identify predictors of response to anthracycline-based chemotherapy (5-fluoro-uracil, epirubicin, cyclophosphamide (FEC)) in locally advanced primary breast cancer (LAPC).Methodsa total of 91 LAPC patients were treated with six cycles of FEC before surgery. Protein expression of nine biomarkers (topoisomerase2α (Topo2α), ER, PR, HER2, Ki67, p53, EGFR, CK5/6 and CK14) was assessed in pre-chemotherapy core biopsies using immunohistochemistry (IHC) and results correlated with clinical and pathological response.Resultsclinical (cCR) and pathological (pCR) complete response were seen in 34.1% (n=31) and 20% (n=18), respectively. Pathological complete response was concordant with cCR in 14/31 cases; in four cases of cPR with palpable residual breast tumours, histology showed fibrous tissue only (pCR). On univariate analysis, pre-chemotherapy high expression of Topo2α protein (P=0.031), and negativity for ER and EGFR (P=0.001 and P=0.005, respectively) correlated with pCR. Positivity for p53 also showed significance (P=0.015), whereas basal phenotype, HER2, and all the clinicopathological variables of LAPC included in this study did not show significant correlation with response. On multivariate analysis, Topo2α expression had the strongest correlation with pCR (P=0.021) followed by EGFR (P=0.044).Conclusionthe study suggests that pre-chemotherapy Topo2α protein expression measured by IHC strongly correlates with pathological CR to neo-adjuvant anthracyclines in this group of LAPC studied.
| S-EPMC3008601 | biostudies-literature
Project description:A subset of breast cancer patients benefits from preoperative bevacizumab and chemotherapy, but validated predictive biomarkers are lacking. Here, we aimed to evaluate tissue-based angiogenesis markers for potential predictive value regarding response to neoadjuvant bevacizumab treatment in breast cancer. In this randomized 1:1 phase II clinical trial, 132 patients with large or locally advanced HER2-negative tumors received chemotherapy ± bevacizumab. Dual Factor VIII/Ki-67 immunohistochemical staining was performed on core needle biopsies at baseline and week 12. Microvessel density (MVD), proliferative microvessel density (pMVD; Factor VIII/Ki-67 co-expression), glomeruloid microvascular proliferation (GMP), and a gene expression angiogenesis signature score, were studied in relation to pathologic complete response (pCR), clinico-pathologic features and intrinsic molecular subtype. We found that high baseline MVD (by median) significantly predicted pCR in the bevacizumab-arm (odds ratio 4.9, P = 0.012). High pMVD, presence of GMP, and the angiogenesis signature score did not predict pCR, but were associated with basal-like (P ≤ 0.009) and triple negative phenotypes (P ≤ 0.041). pMVD and GMP did also associate with high-grade tumors (P ≤ 0.048). To conclude, high baseline MVD significantly predicted response to bevacizumab treatment. In contrast, pMVD, GMP, and the angiogenesis signature score, did not predict response, but associated with aggressive tumor features, including basal-like and triple-negative phenotypes.
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