Objective Oesophageal squamous cell carcinoma (ESCC) is a heterogeneous disease with variable outcomes that are challenging to predict. A better understanding of the biology of ESCC recurrence is needed to improve patient care. Our goal was to identify small non-coding RNAs (sncRNAs) that could predict the likelihood of recurrence after surgical resection and to uncover potential molecular mechanisms that dictate clinical heterogeneity. Design We developed a robust prediction model for recurrence based on the analysis of the expression profile data of sncRNAs from 108 fresh frozen ESCC specimens as a discovery set and assessment of the associations between sncRNAs and recurrence-free survival (RFS). We also evaluated the mechanistic and therapeutic implications of sncRNA obtained through integrated analysis from multiple datasets. Results We developed a risk assessment score (RAS) for recurrence with three sncRNAs (microRNA (miR)-223, miR-1269a and nc886) whose expression was significantly associated with RFS in the discovery cohort (n=108). RAS was validated in an independent cohort of 512 patients. In multivariable analysis, RAS was an independent predictor of recurrence (HR, 2.27; 95% CI, 1.26 to 4.09; p=0 . 007). This signature implies the expression of ΔNp63 and multiple alterations of driver genes like PIK3CA. We suggested therapeutic potentials of immune checkpoint inhibitors in low-risk patients, and Polo-like kinase inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and histone deacetylase inhibitors in high-risk patients. Conclusion We developed an easy-to-use prognostic model with three sncRNAs as robust prognostic markers for postoperative recurrence of ESCC. We anticipate that such a stratified and systematic, tumour-specific biological approach will potentially contribute to significant improvement in ESCC treatment.
Expression of PD-1 ligands by tumors and interaction with PD-1–expressing T cells in the tumor microenvironment can result in tolerance. Therapies targeting this coinhibitory axis have proven clinically successful in the treatment of metastatic melanoma, non–small cell lung cancer, and other malignancies. Therapeutic agents targeting the epigenetic regulatory family of histone deacetylases (HDAC) have shown clinical success in the treatment of some hematologic malignancies. Beyond direct tumor c...
#2Karen L. Reckamp(City of Hope National Medical Center)H-Index: 57
Last. David R. Spigel(Sarah Cannon Research Institute)H-Index: 85
view all 25 authors...
BackgroundPatients with advanced squamous-cell non–small-cell lung cancer (NSCLC) who have disease progression during or after first-line chemotherapy have limited treatment options. This randomized, open-label, international, phase 3 study evaluated the efficacy and safety of nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint–inhibitor antibody, as compared with docetaxel in this patient population. MethodsWe randomly assigned 272 patients to receive nivolumab, at a dose ...
Colorectal cancer (CRC), like many solid tumours, progresses from adenomas to carcinomas in a sequence that leads to metastasis. Here the authors show that miR1269 plays a role in CRC relapse and metastasis by regulating TGF-β activity.
#1Padmanee Sharma(University of Texas MD Anderson Cancer Center)H-Index: 72
#2James P. Allison(University of Texas MD Anderson Cancer Center)H-Index: 147
Immune checkpoint therapy, which targets regulatory pathways in T cells to enhance antitumor immune responses, has led to important clinical advances and provided a new weapon against cancer. This therapy has elicited durable clinical responses and, in a fraction of patients, long-term remissions where patients exhibit no clinical signs of cancer for many years. The way forward for this class of novel agents lies in our ability to understand human immune responses in the tumor microenvironment. ...
Last. David Forman(IARC: International Agency for Research on Cancer)H-Index: 103
view all 4 authors...
Objective The two major histological types of oesophageal cancer—adenocarcinoma (AC) and squamous cell carcinoma (SCC)—are known to differ greatly in terms of risk factors and epidemiology. To date, global incidence estimates for individual subtypes are still lacking. This study for the first time quantified the global burden of oesophageal cancer by histological subtype. Design Where available, data from Cancer Incidence in Five Continents Vol. X (CI5X) were used to compute, age-specific, sex-s...
#2Freddie Bray(IARC: International Agency for Research on Cancer)H-Index: 119
Last. Ahmedin Jemal(ACS: American Cancer Society)H-Index: 139
view all 6 authors...
Cancer constitutes an enormous burden on society in more and less economically developed countries alike. The occurrence of cancer is increasing because of the growth and aging of the population, as well as an increasing prevalence of established risk factors such as smoking, overweight, physical inactivity, and changing reproductive patterns associated with urbanization and economic development. Based on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million deaths occurred in ...
#2Ivano Amelio(University of Leicester)H-Index: 29
Last. Gennaro Melino(University of Rome Tor Vergata)H-Index: 29
view all 4 authors...
MicroRNAs (miRs) are a class of small noncoding RNAs that suppress the expression of protein-coding genes by repressing protein translation. Although the roles that miRs and the miR processing machinery have in regulating epithelial stem cell biology are not fully understood, their fundamental contributions to these processes have been demonstrated over the last few years. The p53-family member p63 is an essential transcription factor for epidermal morphogenesis and homeostasis. p63 functions as...
#1Yibo Gao(Academy of Medical Sciences, United Kingdom)H-Index: 18
#2Zhao Li Chen(Academy of Medical Sciences, United Kingdom)H-Index: 1
Last. Jie He(Peking Union Medical College)H-Index: 54
view all 33 authors...
Jie He and colleagues report exome sequencing of 113 tumor-normal pairs of esophageal squamous cell carcinoma. They highlight mutations in genes involved in cell cycle and apoptosis regulation, histone modifier genes and genes encoding members of the Hippo and Notch pathways.
#1Kwang Soo Lee(UTMB: University of Texas Medical Branch)H-Index: 3
#2Jong Lyul Park(Korea Research Institute of Bioscience and Biotechnology)H-Index: 11
Last. Yong Sun Lee(UTMB: University of Texas Medical Branch)H-Index: 19
view all 16 authors...
// Kwang-Soo Lee 1,2,* , Jong-Lyul Park 3,4,* , Kwanbok Lee 1 , Lauren E. Richardson 1,5 , Betty H. Johnson 1 , Hyun-Sung Lee 6 , Ju-Seog Lee 6 , Sang-Bae Kim 6 , Oh-Hyung Kwon 3 , Kyu Sang Song 7 , Yong Sung Kim 3,4 , Hassan Ashktorab 8 , Duane T. Smoot 8 , Sung Ho Jeon 2 , Seon-Young Kim 3,4 and Yong Sun Lee 1 1. Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX77555-1072, USA 2. Department of Life Science and Center for Aging and Health Ca...
Using whole-genome and whole-exome sequencing, this study identifies eight significantly mutated genes in oesophageal squamous cell cancer, including two genes, ADAM29 and FAM135B, not previously associated with this cancer type.
According to the 2018 global cancer statistics, the incidence and mortality rates of breast cancer are increasing gradually, which seriously threatens the health of women. MicroRNA-223-3p (miR-223-3p) can promote the proliferation and invasion of breast cancer cells. Hippo/Yes-related protein (Yap) signaling pathway activation has been found in a variety of tumors. The present study aimed to investigate the potential mechanism of miR-223-3p in breast cancer. The Cell Counting Kit-8 assay was use...
BackgroundDespite the profound number of malignant pleural mesothelioma (MPM) patients now treated with PD-1 blockade, insight into the underpinnings of rational therapeutic strategies to treat resistance to checkpoint immunotherapy remain unrealized. Our objective was to develop a novel therapeutic approach to overcome primary resistance to PD-1 blockade in MPM. MethodsWe generated a transcriptome signature of resistance to PD-1 blockade in MPM patients treated with nivolumab (4 responders and ...
Last. Alberto Tonda(Université Paris-Saclay)H-Index: 14
view all 7 authors...
Circulating microRNAs (miRNA) are small noncoding RNA molecules that can be detected in bodily fluids without the need for major invasive procedures on patients. miRNAs have shown great promise as biomarkers for tumors to both assess their presence and to predict their type and subtype. Recently, thanks to the availability of miRNAs datasets, machine learning techniques have been successfully applied to tumor classification. The results, however, are difficult to assess and interpret by medical ...
To identify candidate key genes and miRNAs associated with esophageal squamous cell carcinoma (ESCC) development and prognosis, the gene expression profiles and miRNA microarray data including GSE20347, GSE38129, GSE23400, and GSE55856 were downloaded from the Gene Expression Omnibus (GEO) database. Clinical and survival data were retrieved from The Cancer Genome Atlas (TCGA). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of differentially expressed genes (DEGs) was ...
#1Hee Jin Jang(SNU: Seoul National University)H-Index: 16
#2Hyun-Sung Lee(BCM: Baylor College of Medicine)H-Index: 25
Last. Young Tae Kim(SNU: Seoul National University)H-Index: 79
view all 7 authors...
Abstract Objective We set out to investigate whether transcriptome-based molecular subtypes in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are predictive of response to PD-1 blockade. Methods Molecular classification of non-small cell lung cancer (NSCLC) was performed by unsupervised clustering of mRNA sequencing data from 87 LUAD and 101 LUSC specimens, and molecular subtypes were characterized according to their immunogenomic determinants. A prediction algorithm of molec...
Nc886 is a regulatory non-coding RNA (ncRNA) whose expression is frequently silenced in malignancies. In the case of esophageal squamous cell carcinoma (ESCC), nc886 silencing is associated with shorter survival of patients, suggesting nc886′s tumor suppressor role in ESCC. However, this observation has not been complemented by an in-detail study about nc886′s impact on gene expression and cellular phenotypes. Here we have shown that nc886 inhibits AKT, a key protein in a renowned pro-survival p...
#1Tongyan Liu(Nanjing Medical University)H-Index: 2
#2Panqi Fang(Nanjing Medical University)H-Index: 2
Last. Qin Zhang(Nanjing Medical University)H-Index: 9
view all 12 authors...
Oesophageal cancer (ESCA) is a clinically challenging disease with poor prognosis and health‐related quality of life. Here, we investigated the transcriptome of ESCA to identify high risk‐related signatures. A total of 159 ESCA patients of The Cancer Genome Atlas (TCGA) were sorted by three phases. In the discovery phase, differentially expressed transcripts were filtered; in the training phase, two adjusted Cox regressions and two machine leaning models were used to construct and estimate signa...
Last. Wei Wang(Nanjing Medical University)H-Index: 5
view all 12 authors...
BACKGROUND: The poor outcome of patients with esophageal squamous cell carcinoma (ESCC) highlights the importance of the identification of novel effective prognostic biomarkers. We aimed to identify a clinically applicable prognostic immunohistochemistry (IHC) panel for ESCC. METHODS: An integrated analysis was performed to screen and establish a prognostic panel using exome sequencing profile from 81 pairs of ESCC samples and RNA expression microarray data from 119 ESCC subjects. Two independen...
#2Malla Rama Rao(GITAM: Gandhi Institute of Technology and Management)
Gastrointestinal (GI) malignancies like esophageal, gastric, colorectal cancers, etc. are responsible for 22% cancer deaths and are the third most cause of cancer related deaths. GI cancers are treated by surgery, radiotherapy, and chemotherapy. The overall survival rate (5 years of survival) after the surgery is very poor in patients with GI cancers. To increase the survival rate adjuvant therapies like chemotherapy and radiotherapy were performed. As GI cancers are diagnosed at the advanced st...
