Biological Significance of Tumor Heterogeneity in Esophageal Squamous Cell Carcinoma

Abstract

Esophageal squamous cell carcinoma (ESCC) is a common and aggressive malignancy, with hitherto dismal clinical outcome. Genomic analyses of patient samples reveal a complex heterogeneous landscape for ESCC, which presents in both intertumor and intratumor forms, manifests at both genomic and epigenomic levels, and contributes significantly to tumor evolution, drug resistance, and metastasis. Here, we review the important molecular characteristics underlying ESCC heterogeneity, with an emphasis on genomic aberrations and their functional contribution to cancer evolutionary trajectories. We further discuss how novel experimental tools, including single-cell sequencing and three-dimensional organoids, may advance our understanding of tumor heterogeneity. Lastly, we suggest that deciphering the mechanisms governing tumor heterogeneity holds the potential to developing precision therapeutics for ESCC patients.

m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

“…There are two main subtypes in ESCA, called ESCC and EAC, respectively ( 27 , 28 ). ESCC is mainly in the East Asian population, whereas EAC mainly occurs in Western countries ( 29 ). About half of the newly diagnosed ESCA cases in the world occur in China every year ( 30 , 31 ).…”

“…ESCA is considered to be a multifactor, multigene, and multistage complicated disease ( 27 ). Its occurrence is closely related to chronic nitrosamine stimulation, inflammation and trauma, genetic and epigenetic modification, and other factors ( 29 , 32 ). Operation, radiotherapy, and chemotherapy are still the main treatment methods for ESCA, but inoperableness and radiochemotherapy resistance limit the clinical effect ( 29 ).…”

“…Its occurrence is closely related to chronic nitrosamine stimulation, inflammation and trauma, genetic and epigenetic modification, and other factors ( 29 , 32 ). Operation, radiotherapy, and chemotherapy are still the main treatment methods for ESCA, but inoperableness and radiochemotherapy resistance limit the clinical effect ( 29 ). Therefore, identification of new molecular markers and therapeutic targets is still an urgent need.…”

Circular RNA hsa_circ_0000654 promotes esophageal squamous cell carcinoma progression by regulating the miR‐149‐5p/IL‐6/STAT3 pathway

“…Esophageal cancer is the eighth most‐common cancer in the world and the sixth leading cause of cancer death . Esophageal squamous cell carcinoma (ESCC) is the major histological subtype, especially in certain countries, such as China . Despite the rapid development of medical technology and continuous improvements in early diagnostic techniques, advanced ESCC cases still account for ~50% of cases and exhibit a 5‐year survival rate of only 15–25% .…”

“…1,2 Esophageal squamous cell carcinoma (ESCC) is the major histological subtype, especially in certain countries, such as China. 3 Despite the rapid development of medical technology and continuous improvements in early diagnostic techniques, advanced ESCC cases still account for~50% of cases and exhibit a 5-year survival rate of only 15-25%. 4,5 Therefore, there is an urgent need to further understand the ESCC progression mechanism to explore novel therapeutic targets.…”