A three-lncRNA signature of pretreatment biopsies predicts pathological response and outcome in esophageal squamous cell carcinoma with neoadjuvant chemoradiotherapy.
Ontology highlight
ABSTRACT:
SUBMITTER: Zhang C
PROVIDER: S-EPMC7448795 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
Publications
A three-lncRNA signature of pretreatment biopsies predicts pathological response and outcome in esophageal squamous cell carcinoma with neoadjuvant chemoradiotherapy.
Zhang Chaoqi C Zhang Zhihui Z Zhang Guochao G Xue Liyan L Yang Haijun H Luo Yuejun Y Zheng Xiaoli X Zhang Yonglei Y Yuan Yufen Y Lei Ruixue R Yang Zhaoyang Z Zheng Bo B Zhang Zhen Z Wang Le L Che Yun Y Wang Sihui S Wang Feng F Fang Lingling L Zeng Qingpeng Q Li Jiagen J Gao Shugeng S Xue Qi Q Sun Nan N He Jie J He Jie J
Clinical and translational medicine 20200801 4
<h4>Background</h4>Current strategies are insufficient to predict pathologically complete response (pCR) for esophageal squamous cell carcinomas (ESCCs) before treatment. Here, we aim to develop a novel long noncoding RNA (lncRNA) signature for pCR and outcome prediction of ESCCs through a multicenter analysis for a Chinese population.<h4>Methods</h4>Differentially expressed lncRNAs (DELs) between pCRs and less than pCR (<pCR) in the pretreated cancer biopsies were identified from 28 cases in Gu ...[more]
Similar Datasets
Project description:No clinically available biomarkers can predict pathological complete response (pCR) for esophageal squamous cell carcinomas (ESCCs) with neoadjuvant chemoradiotherapy (nCRT). Considering that antitumor immunity status is an important determinant for nCRT, we performed an integrative analysis of immune-related gene profiles from pretreatment biopsies and constructed the first individualized immune signature for pCR and outcome prediction of ESCCs through a multicenter analysis. During the discovery phase, 14 differentially expressed immune-related genes (DEIGs) with greater than a twofold change between pCRs and less than pCRs (<pCRs) were revealed from 28 pretreatment tumors in a Guangzhou cohort using microarray data. Ten DEIGs were verified by qPCR from 30 cases in a Beijing discovery cohort. Then, a four-gene-based immune signature (SERPINE1, MMP12, PLAUR, and EPS8) was built based on the verified DEIGs from 71 cases in a Beijing training cohort, and achieved a high accuracy with an area under the receiver operating characteristic curve (AUC) of 0.970. The signature was further validated in an internal validation cohort and an integrated external cohort (Zhengzhou and Anyang cohorts) with AUCs of 0.890 and 0.859, respectively. Importantly, a multivariate analysis showed that the signature was the only independent predictor for pCR. In addition, patients with high predictive scores showed significantly longer overall and relapse-free survival across multiple centers (P < 0.05). This is the first, validated, and clinically applicable individualized immune signature of pCR and outcome prediction for ESCCs with nCRT. Further prospective validation may facilitate the combination of nCRT and immunotherapy.
| S-EPMC7471268 | biostudies-literature
Project description:BackgroundsIn this study, we evaluated the factors associated with a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) for esophageal squamous cell carcinoma (ESCC).MethodsPre-nCRT parameters in ESCC patients treated between 1999 and 2006 were analyzed to identify predictors of pCR. All patients received 5-fluorouracil/cisplatin-based chemotherapy and external beam radiation followed by scheduled esophagectomy. Variables were analyzed using univariate and multivariate analyses with pCR as the dependent variable. Estimated pCR rate was calculated with a regression model.ResultsFifty-nine (20.9%) of 282 patients achieved pCR. Univariate analysis identified four patient factors (age, smoking status, drinking history and hypertension), one pre-nCRT parameter (tumor length) as significant predictors of pCR (all P <0.05). On multivariate analysis, tumor length ?3 cm (favorable, odds ratio (OR): 4.85, P?=?0.001), patient age >55 years (favorable, OR: 1.95, P?=?0.035), and being a non-smoker (favorable, OR: 3.6, P?=?0.003) were independent predictors of pCR. The estimated pCR rates based on a logistic regression including those three predictors were 71%, 35 to approximately 58%, 19 to approximately 38%, and 12% for patients with 3, 2, 1 and 0 predictors, respectively.ConclusionAge, smoking habit and tumor length were important pCR predictors. These factors may be used to predict outcomes for ESCC patients receiving nCRT, to develop risk-adapted treatment strategies, and to select patients who could participate in trials on new therapies.
| S-EPMC4050419 | biostudies-literature
Project description:BackgroundThis study was conducted to validate a pretreatment (i.e. prior to neoadjuvant chemoradiotherapy) pathological staging system in the resection specimen after neoadjuvant chemoradiotherapy for esophageal cancer. The study investigated the prognostic value of pretreatment pathological T and N categories (prepT and prepN categories) in both an independent and a combined patient cohort.MethodsPatients with esophageal cancer treated with neoadjuvant chemotherapy and esophagectomy between 2012 and 2015 were included. PrepT and prepN categories were estimated based on the extent of tumor regression and regressional changes of lymph nodes in the resection specimen. The difference in Akaike's information criterion (ΔAIC) was used to assess prognostic performance. PrepN and ypN categories were combined to determine the effect of nodal sterilization on prognosis. A multivariable Cox regression model was used to identify combined prepN and ypN categories as independent prognostic factors.ResultsThe prognostic strength of the prepT category was better than the cT and ypT categories (ΔAIC 7.7 vs. 3.0 and 2.9, respectively), and the prognostic strength of the prepN category was better than the cN category and similar to the ypN category (ΔAIC 29.2 vs. - 1.0 and 27.9, respectively). PrepN + patients who became ypN0 had significantly worse survival than prepN0 patients (2-year overall survival 69% vs. 86% in 137 patients; p = 0.044). Similar results were found in a combined cohort of 317 patients (2-year overall survival 62% vs. 85%; p = 0.002). Combined prepN/ypN stage was independently associated with overall survival.ConclusionsThese results independently confirm the prognostic value of prepTNM staging. PrepTNM staging is of additional prognostic value to cTNM and ypTNM. PrepN0/ypN0 patients have a better survival than prepN +/ypN0 patients.
| S-EPMC7060166 | biostudies-literature
Project description:Esophageal squamous cell carcinoma (ESCC) is one of the most common types of cancer and the leading causes of cancer-related mortality worldwide, especially in Eastern Asia. Here, we downloaded the microarray data of lncRNA expression profiles of ESCC patients from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data sets and divided into training, validation and test set. The random survival forest (RSF) algorithm and Cox regression analysis were applied to identify a seven-lncRNA signature. Then the predictive ability of the seven-lncRNA signature was evaluated in the validation and test set using Kaplan-Meier test, time-dependent receiver operating characteristic (ROC) curves and dynamic area under curve (AUC). Stratified analysis and multivariate Cox regression also demonstrated the independence of the signature in prognosis prediction from other clinical factors. Besides, the predict accuracy of lncRNA signature was much better than that of tumor-node-metastasis (TNM) stage in all the three sets. LncRNA combined with TNM displayed better prognostic predict ability than either alone. The role of LINC00173 from the signature in modulating the proliferation and cell cycle of ESCC cells was also observed. These results indicated that this seven-lncRNA signature could be used as an independent prognostic biomarker for prognosis prediction of patients with ESCC.
| S-EPMC5995883 | biostudies-literature
Project description:BackgroundNeoadjuvant chemoradiotherapy (neo-CRT) plus surgery has greatly improved the prognosis of locally advanced esophageal cancer (EC) patients. But which factors may influence the pathological tumor response and long-term survival remains unclear. The purpose of this study was to identify the prognostic biomarkers of locally advanced EC patients receiving neo-CRT.MethodsWe reviewed the data of 72 patients with cT2-4N0-3M0 EC who underwent neo-CRT at our hospital. The patients received intensity-modulated radiation therapy with a total radiation dose of 41.4-60.0 Gy. Most patients received platinum + paclitaxel-based combination regimens every three weeks for 2-4 cycles. The recorded data included age, sex, smoking history, alcohol use, histology, tumor location, clinical TNM stage, tumor length, gross tumor volume (GTV), GTV of primary tumor (GTVp), GTV of lymph nodes (GTVn), radiation dose, and number of chemotherapy cycles. Overall survival (OS), progression-free survival (PFS), and pathological complete response (pCR) were analyzed.ResultsThe 3-year OS and PFS rates of these patients who underwent neo-CRT were 51.14% and 43.28%, respectively. In the univariate analyses, smoking history, clinical stage, GTV, GTVp, and GTVn were significantly associated with OS, whereas alcohol use, GTV, GTVp, and GTVn were significantly associated with PFS. Furthermore, in the multivariate analysis, GTV was an independent prognostic predictor of OS (hazard ratio (HR): 14.14, 95% confidence interval (CI): 3.747-53.33, P < 0.0001) and PFS (HR: 6.090, 95% CI: 2.398-15.47, P < 0.0001). In addition, GTV < 60.50 cm3 compared to > 60.50 cm3 was significantly associated with higher pCR rate (59.3% and 27.8%, respectively, P = 0.038). High dose (> 50 Gy) and increased number of chemotherapy cycles (≥ 3) didn't improve the OS or PFS in patients with GTV > 60.50 cm3.ConclusionGTV was an independent prognostic factor of long-term survival in EC patients, which may be because GTV is associated with histological response to neo-CRT. Additionally, patients with GTV > 60.50 cm3 didn't benefit from increased radiation dose or increased number of chemotherapy cycles.
| S-EPMC9209710 | biostudies-literature
Project description:Neoadjuvant radiochemotherapy (nRCT) followed by surgery has become the gold standard treatment in patients with locally advanced esophageal cancer. The pathological response is an important predictor in such patients. This work represents a single-center analysis investigating the impact of pathological complete response (pCR) on treatment outcome.All patients treated with nRCT followed by surgery between January 2005 and December 2015 were reviewed. The patients were categorized into two groups according to the pathological response following nRCT: pCR group and non-pCR group.Fifty-six patients with invasive cancer, 23 patients (41.1%) achieved pCR and 33 patients had non-pCR (58.9%) following nRCT. The average age was 62 years (±9.1), and most patients were males (83.9%). Histological types included squamous cell carcinoma (75%) and adenocarcinoma (25%). The total radiation dose was 45 Gy in 76.8% of the patients and 50.4 Gy in 23.2%. The median overall survival (OS) of the entire group was 3.5±1.2 years, and the 5-year OS rate was 38.2%, while the median disease-free survival (DFS) was 2.1±0.4 years and the 5-year DFS rate was 33.1%. The patients who achieved pCR had significantly higher 5-year OS and 5-year DFS rates: 47.2% and 48% compared to 27.3% and 21% for the non-pCR patients respectively (P=0.04, 0.03). The median time of local recurrence was 3.8±0.4 years in pCR group and 1.8±0.2 years in non-pCR group (P=0.01), while the median time of distant metastases in pCR group was 1.2±0.5 years and 1.1±0.2 years in non-pCR group (P=0.6).Complete pathological response predicts significantly higher rates of OS and DFS in patients with locally advanced esophageal cancer treated with nRCT followed by surgery.
| S-EPMC6106005 | biostudies-other
Project description:After neoadjuvant chemoradiotherapy (NCRT) in locally advanced esophageal squamous cell cancer (ESCC), roughly 40% of the patients may achieve pathologic complete response (pCR). Those patients may benefit from organ-saving strategy if the probability of pCR could be correctly identified before esophagectomy. A reliable approach to predict pathological response allows future studies to investigate individualized treatment plans.MethodAll eligible patients treated in our center from June 2012 to June 2019 were retrospectively collected. Radiomics features extracted from pre-/post-NCRT CT images were selected by univariate logistic and LASSO regression. A radiomics signature (RS) developed with selected features was combined with clinical variables to construct RS+clinical model with multivariate logistic regression, which was internally validated by bootstrapping. Performance and clinical usefulness of RS+clinical model were assessed by receiver operating characteristic (ROC) curves and decision curve analysis, respectively.ResultsAmong the 121 eligible patients, 51 achieved pCR (42.1%) after NCRT. Eighteen radiomics features were selected and incorporated into RS. The RS+clinical model has improved prediction performance for pCR compared with the clinical model (corrected area under the ROC curve, 0.84 vs. 0.70). At the 60% probability threshold cutoff (i.e., the patient would opt for observation if his probability of pCR was >60%), net 13% surgeries could be avoided by RS+clinical model, equivalent to implementing organ-saving strategy in 31.37% of the 51 true-pCR cases.ConclusionThe model built with CT radiomics features and clinical variables shows the potential of predicting pCR after NCRT; it provides significant clinical benefit in identifying qualified patients to receive individualized organ-saving treatment plans.
| S-EPMC7933499 | biostudies-literature
Project description:Large primary tumor volume has been identified as a poor prognostic factor of esophageal squamous cell carcinoma (ESCC) treated with definitive concurrent chemoradiotherapy (CCRT). However, when neoadjuvant CCRT and surgery are adopted, the prognostic impact of primary tumor and lymph node (LN) volume on clinical outcomes in ESCC remains to be elucidated. This study included 107 patients who received neoadjuvant CCRT and surgery for ESCC. The volume of the primary tumor and LN was measured using radiotherapy planning computed tomography scans, and was correlated with overall survival (OS), disease-free survival (DFS), and cancer failure pattern. The median OS was 24.2 months (IQR, 11.1-93.9) after a median follow-up of 18.4 months (IQR, 8.1-40.7). The patients with a baseline LN volume > 7.7 ml had a significantly worse median OS compared to those with smaller LN volume (18.8 vs. 46.9 months, p = 0.049), as did those with tumor regression grade (TRG) 3-5 after CCRT (13.9 vs. 86.7 months, p < 0.001). However, there was no association between OS and esophageal tumor volume (p = 0.363). Multivariate analysis indicated that large LN volume (HR 1.753, 95% CI 1.015-3.029, p = 0.044) and high TRG (HR 3.276, 95% CI 1.556-6.898, p = 0.002) were negative prognostic factors for OS. Furthermore, large LN volume was linked to increased locoregional failure (p = 0.033) and decreased DFS (p = 0.041). In conclusion, this study demonstrated that large LN volume is correlated with poor OS, DFS, and locoregional control in ESCC treated with neoadjuvant CCRT and esophagectomy.
| S-EPMC10977715 | biostudies-literature
Project description:Background Neoadjuvant chemoradiotherapy (neo-CRT) in combination with surgery increases survival compared to surgery alone, as indicated by the esophageal squamous cell carcinoma (ESCC) treatment recommendations. However, the benefits of neo-CRT are diverse among patients. Consequently, the development of new biomarkers that correlate with neo-CRT might be important for the treatment of ESCC. Methods The differentially expressed genes (DEG) between responsive and resistant samples from the GSE45670 dataset were obtained. On the TCGA dataset, survival analysis was performed to identify prognosis-related-EMT-genes. For EMT score model construction, lasso regression analysis in the TCGA cohort was used to identify the genes. In the TCGA-ESCC cohort, age, stage, and EMT score were used to construct a nomogram. Results In total, 10 prognosis-related-EMT-genes were obtained. These 10 genes consisted of 6 risky genes and 4 protective genes. Based on the lasso analysis and univariate Cox regression, an EMT score model consisting of 7 genes (CLEC18A, PIR, KCNN4, MST1R, CAPG, ALDH5A1, and COX7B) was identified. ESCC patients with a high EMT score have a worse prognosis. These genes were differentially expressed between responsive and resistant patients and had a high accuracy for distinguishing resistant and responsive patients. Conclusions The identified genes have the potential to function as molecular biomarkers for predicting ESCC patients' resistance to neo-CRT. This research may aid in the elucidation of the molecular processes driving resistance and the identification of targets for improving the prognosis for ESCC.
| S-EPMC9442501 | biostudies-literature
Project description:Despite the use of multimodal treatment, survival of esophageal cancer (EC) patients remains poor. One proposed explanation for the relatively poor response to cytotoxic chemotherapy is intratumor heterogeneity. The aim was to establish a statistical model to objectively measure intratumor heterogeneity of the proportion of tumor (IHPoT) and to use this newly developed method to measure IHPoT in the pretreatment biopsies from from EC patients recruited to the OE02 trial. A statistical mixed effect model (MEM) was established for estimating IHPoT based on variation in hematoxylin/eosin (HE) stained pretreatment biopsy pieces from the same individual in 218 OE02 trial patients (103 treated by chemotherapy and surgery (chemo+surgery); 115 patients treated by surgery alone). The relationship between IHPoT, prognosis, chemotherapy survival benefit, and clinicopathological variables was assessed. About 97 (44.5%) and 121 (55.5%) ECs showed high and low IHPoT, respectively. There was no significant difference in IHPoT between surgery (median [range], 0.1637 [0-3.17]) and chemo+surgery (median [range], 0.1692 [0-2.69]) patients (P = 0.43). Chemo+surgery patients with low IHPoT had a significantly longer survival than surgery patients (HR = 1.81, 95% CI: 1.20-2.75, P = 0.005). There was no survival difference between chemo+surgery and surgery patients with high IHPoT (HR = 1.15, 95% CI: 0.72-1.81, P = 0.566). This is the first study suggesting that IHPoT measured in the pretreatment biopsy can predict chemotherapy survival benefit in EC patients. IHPoT may represent a clinically useful biomarker for patient treatment stratification. Future studies should determine if pathologists can reliably estimate IHPoT.
| S-EPMC7397482 | biostudies-literature