689 MMS22L EXPRESSION AS A PREDICTIVE BIOMARKER FOR THE EFFICACY OF NEOADJUVANT CHEMORADIOTHERAPY IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Long-term survival in esophageal squamous cell carcinoma (ESCC) is related with pathological response after neoadjuvant chemoradiation therapy (NCRT) followed by surgery. However, effective biomarkers for prediction of pathologic response is still lacking. Therefore, a systematic analysis focusing on genes associated with efficacy of chemoradiotherapy in ESCC will provide valuable insights to understand the molecular features. Methods We collected genes associated with efficacy of chemoradiotherapy by screening publications deposited in PubMed. A specific subnetwork was constructed using Steiner minimum tree algorithm. Then the correlations between gene expression and prognosis of ESCC patients was analyzed using Kaplan–Meier Plotter online resources. The key gene expression was evaluated by quantitative real-time polymerase chain reaction, western blotting analysis and immunohistochemical staining. The predictive performance of biomarkers was estimated using receiver operating characteristic (ROC) curve analysis. Results We identified 101 genes associated with efficacy of chemoradiotherapy. Moreover, specific molecular network included some potential related genes, such as CUL3, MUC13, MMS22L, MME, UBC, VAPA, CYP1B1 and UGDH. MMS22L mRNA expression level had most significant association with the ESCC patient outcome (P < 0.01). Furthermore, MMS22L was downregulated at both the mRNA (P < 0.01) and protein levels in tumor compared with normal tissues. Lymph node metastasis was significantly associated with low MMS22L expression (P < 0.001). MMS22L levels were inversely correlated with NCRT response in ESCC (P < 0.01). MMS22L yielded an area under the ROC curve (AUC) of 0.847 (P < 0.01). Conclusion Low MMS22L expression could be an effective predictive biomarker for resistance to NCRT in ESCC.

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SUVmax Reduction Predicts Long-Term Survival in Patients of Non-pCR Both in the Tumor and Lymph Nodes after Neoadjuvant Chemoradiotherapy in Esophageal Squamous Cell Carcinoma

10.21203/rs.3.rs-150878/v1 ◽

2021 ◽

Author(s):

Yushi Nagaki ◽

Satoru Motoyama ◽

Yusuke Sato ◽

Akiyuki Wakita ◽

Hiromu Fujita ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Prognostic Factors ◽

Esophageal Squamous Cell Carcinoma ◽

Lymph Nodes ◽

Cell Carcinoma ◽

Squamous Cell ◽

Neoadjuvant Chemoradiotherapy ◽

Reduction Rate ◽

Term Survival

Abstract Background: A pathological complete response (pCR) after neoadjuvant chemoradiotherapy (NACRT) ensures long-term survival in esophageal squamous cell carcinoma (ESCC) patients following esophagectomy, but pCR patients are a minority. The aim here was to identify prognostic factors in patients with non-pCR ESCC after NACRT. Methods: This is a retrospective study. Investigated were 5-year overall survival (OS), disease-specific survival (DSS), and relapse-free survival (RFS) among non-pCR ESCC patients divided into pT0N0, primary site pCR (pT0N+), lymph node pCR (pT+N0), and non-pCR in both the tumor and lymph nodes (pT+N+) subgroups after NACRT and esophagectomy. Focusing on the SUVmax reduction rate in the primary tumor in 88 patients who underwent FDG-PET before and after NACRT, we used univariate and multivariate Cox proportional hazard models to identify prognostic factors.Results: Although there were no significant survival differences among non-pCR ESCC patients with pT0N+, pT+N0, or pT+N+, and survival rate among pT+N+ patients was the poorest. After setting a 60% cutoff for the SUVmax reduction rate in the tumor, RFS curves for non-pCR patients significantly differed between patients above the cutoff and those below it. For pT+N+ patients, the SUVmax reduction rate (<60% vs ≥60%) was an independent prognostic factor of OS, DSS, and RFS.Conclusion: Because ESCC patients with SUVmax reduction rates of <60% in the tumor after NACRT and categorized as pT+N+ after NACRT had significantly poorer prognoses, even after esophagectomy, a change in treatment strategy may be an option to improve survival.

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SUVmax reduction predicts long-term survival in patients of non-pCR both in the tumor and lymph nodes after neoadjuvant chemoradiotherapy in esophageal squamous cell carcinoma

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02208-3 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Yushi Nagaki ◽

Satoru Motoyama ◽

Yusuke Sato ◽

Akiyuki Wakita ◽

Hiromu Fujita ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Prognostic Factors ◽

Lymph Node ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Neoadjuvant Chemoradiotherapy ◽

Reduction Rate ◽

Term Survival

Abstract Background A pathological complete response (pCR) after neoadjuvant chemoradiotherapy (NACRT) ensures long-term survival in esophageal squamous cell carcinoma (ESCC) patients following esophagectomy, but pCR patients are a minority. The aim here was to identify prognostic factors in patients with non-pCR ESCC after NACRT. Methods This is a retrospective study. Investigated were 5-year overall survival (OS), disease-specific survival (DSS), and relapse-free survival (RFS) among non-pCR ESCC patients divided into pT0N0, primary site pCR (pT0N+), lymph node pCR (pT+N0), and non-pCR in both the tumor and lymph node (pT+N+) subgroups after NACRT and esophagectomy. Focusing on the SUVmax reduction rate in the primary tumor in 88 patients who underwent FDG-PET before and after NACRT, we used univariate and multivariate Cox proportional hazard models to identify prognostic factors. Results Although there were no significant survival differences among non-pCR ESCC patients with pT0N+, pT+N0, or pT+N+, survival rate among pT+N+patients was the poorest. After setting a 60% cutoff for the SUVmax reduction rate in the tumor, RFS curves for non-pCR patients significantly differed between patients above the cutoff and those below it. For pT+N+ patients, the SUVmax reduction rate (<60% vs ≥ 60%) was an independent prognostic factor of OS, DSS, and RFS. Conclusion Because ESCC patients with SUVmax reduction rates of <60% in the tumor after NACRT and categorized as pT+N+ after NACRT had significantly poorer prognoses, even after esophagectomy, a change in treatment strategy may be an option to improve survival.

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Using Genomics Feature Selection Method in Radiomics Pipeline Improves Prognostication Performance in Locally Advanced Esophageal Squamous Cell Carcinoma—A Pilot Study

Cancers ◽

10.3390/cancers13092145 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2145

Author(s):

Chen-Yi Xie ◽

Yi-Huai Hu ◽

Joshua Wing-Kei Ho ◽

Lu-Jun Han ◽

Hong Yang ◽

...

Keyword(s):

Gene Expression ◽

Squamous Cell Carcinoma ◽

Feature Selection ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Expression Profiles ◽

Training Set ◽

Term Survival ◽

Test Set

Purpose: To evaluate the prognostic value of baseline and restaging CT-based radiomics with features associated with gene expression in esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiation (nCRT) plus surgery. Methods: We enrolled 106 ESCC patients receiving nCRT from two institutions. Gene expression profiles of 28 patients in the training set were used to detect differentially expressed (DE) genes between patients with and without relapse. Radiomic features that were correlated to DE genes were selected, followed by additional machine learning selection. A radiomic nomogram for disease-free survival (DFS) prediction incorporating the radiomic signature and prognostic clinical characteristics was established for DFS estimation and validated. Results: The radiomic signature with DE genes feature selection achieved better performance for DFS prediction than without. The nomogram incorporating the radiomic signature and lymph nodal status significantly stratified patients into high and low-risk groups for DFS (p < 0.001). The areas under the curve (AUCs) for predicting 5-year DFS were 0.912 in the training set, 0.852 in the internal test set, 0.769 in the external test set. Conclusions: Genomics association was useful for radiomic feature selection. The established radiomic signature was prognostic for DFS. The radiomic nomogram could provide a valuable prediction for individualized long-term survival.

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Gene Expression Profiling Reveals Distinct Molecular Subtypes of Esophageal Squamous Cell Carcinoma in Asian Populations

SSRN Electronic Journal ◽

10.2139/ssrn.3208950 ◽

2018 ◽

Author(s):

Fengling Wang ◽

Zhongyi Yan ◽

Jiajia Lv ◽

Junfang Xin ◽

Yifang Dang ◽

...

Keyword(s):

Gene Expression ◽

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Gene Expression Profiling ◽

Squamous Cell ◽

Expression Profiling ◽

Molecular Subtypes ◽

Asian Populations

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Prognostic impact of lymph node metastasis along the left gastric artery in esophageal squamous cell carcinoma

Journal of Cardiothoracic Surgery ◽

10.1186/s13019-021-01466-2 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Xuan Liu ◽

Leilei Wu ◽

Dongkun Zhang ◽

Peng Lin ◽

Hao Long ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Lymph Node ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cox Regression ◽

Left Gastric Artery ◽

Prognostic Impact ◽

Gastric Artery ◽

Term Survival

Abstract Background Although the incidence of lymph node (LN) metastasis (LNM) along the left gastric artery is high, its relationship with the prognosis in postoperative patients with esophageal squamous cell carcinoma (ESCC) is rarely reported. This study clarified the prognostic impact of LNM along the left gastric artery in postoperative patients with ESCC. Methods This study assessed data of 1521 patients with ESCC who underwent esophagectomy at the Sun Yat-sen University Cancer Center between March 1992 and March 2012. A chi-squared test and Mann-Whitney U test were used to explore the preliminary correlation between clinical factors and LNM along the left gastric artery. Univariate and multivariate Cox regression analyses were used to assess whether LNM along the left gastric artery was an independent predictor of overall survival. Kaplan–Meier analysis and the log-rank test were used to present a classifying effect based on LN status. Results LNM was observed in 598 patients (39.3%) and was found along the branches of the left gastric artery in 256 patients (16.8%). The patients were classified into two groups based on the presence of LNM along the left gastric artery. Patients without LNM along the left gastric artery had better cancer-specific survival than those with positive LNs (P < 0.001). Conclusions This study indicated that LNM along the left gastric artery was an important independent prognostic factor for long-term survival among ESCC patients (P = 0.011).

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Racial Differences in Esophageal Squamous Cell Carcinoma: Incidence and Molecular Features

BioMed Research International ◽

10.1155/2017/1204082 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Shirui Chen ◽

Kai Zhou ◽

Liguang Yang ◽

Guohui Ding ◽

Hong Li

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Cancer ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Racial Differences ◽

Squamous Cell ◽

Geographic Location ◽

Molecular Features ◽

Genome Wide ◽

White Patients

The incidence and histological type of esophageal cancer are highly variable depending on geographic location and race/ethnicity. Here we want to determine if racial difference exists in the molecular features of esophageal cancer. We firstly confirmed that the incidence rate of esophagus adenocarcinoma (EA) was higher in Whites than in Asians and Blacks, while the incidence of esophageal squamous cell carcinoma (ESCC) was highest in Asians. Then we compared the genome-wide somatic mutations, methylation, and gene expression to identify differential genes by race. The mutation frequencies of some genes in the same pathway showed opposite difference between Asian and White patients, but their functional effects to the pathway may be consistent. The global patterns of methylation and expression were similar, which reflected the common characteristics of ESCC tumors from different populations. A small number of genes had significant differences between Asians and Whites. More interesting, the racial differences of COL11A1 were consistent across multiple molecular levels, with higher mutation frequency, higher methylation, and lower expression in White patients. This indicated that COL11A1 might play important roles in ESCC, especially in White population. Additional studies are needed to further explore their functions in esophageal cancer.

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