Simultaneous disruption of circulating miR‐21 and cytotoxic T lymphocytes (CTLs): Prospective diagnostic and prognostic markers for esophageal squamous cell carcinoma (ESCC)

Abstract

Background Esophageal squamous cell carcinoma (ESCC) as the most prominent type of esophageal cancer (EC) in developing countries encompasses a substantial contribution of cancer‐related mortalities and morbidities. Cytotoxic T lymphocytes (CTLs) are the major subset of effector T cells against cancer. However, the microRNAs involved in the development and regulation of CTLs could be disrupted in cancers such as EC. Methods Here, we evaluated the population of IL‐10, TGF‐β, IFN‐γ, and IL‐17a‐producing CD3+CD8+ T cells, their association with the circulating levels of miR‐21 and miR‐29b, and their diagnostic and/or prognostic (after 160 weeks of follow‐up) utilities in 34 ESCC patients (12 newly diagnosed: ND, 24 under‐treatment: UT) and 34 matched healthy donors. Results The population of IL‐10 and TGF‐β‐producing CTLs (CD8+ Tregs) were considerably expanded, in addition to the overexpression of miR‐21 in both groups (ND and UT) of ESCC patients, while the frequency of Tc17 and CD8+ Treg cells increased only in UT patients. The expression means of TGF‐β and IL‐10 in CTLs were considered to be excellent biomarkers (1 ≥ area under the curve: AUC ≥0.9) in distinguishing ESCC patients and associated subgroups from healthy subjects. Moreover, the lower expressions of TGF‐β, IL‐17a, IL‐10, and IFN‐γ in CTLs were associated with ESCC better prognosis. Conclusions The association between the impaired function of CD3+ CD8+ T cell subsets and miR‐21 expression could be introduced as novel therapeutic targets and powerful diagnostic and prognostic markers for ESCC.

SYNGR2 serves as a prognostic biomarker and correlates with immune infiltrates in esophageal squamous cell carcinoma

“…Our results showed that the expression of SYNGR2 was negatively correlated with the infiltration level of T helper cells. Studies have shown that the frequency of Th cells in ESCC patients is significantly reduced, and the average expression of IFN‐ γ in Th cells is also greatly reduced, indicating that the dysregulation of Th‐cell subsets contributes to the occurrence and development of ESCC 14,41,42 . These findings suggest that SYNGR2 may play an important regulatory role in the tumor immune microenvironment and ESCC development.…”

Computational Linguistic Analysis for the Isolation of Propitious miRNA Bio- indicators in Esophageal Cancer

“…MicroRNA-21 regulates the biological behavior of esophageal squamous cell carcinoma by targeting RASA1 20 . Regarding the prognosis of esophageal cancer, the concurrent disruption of circulating miR-21 and cytotoxic T lymphocytes (CTLs) presents as prospective diagnostic and prognostic markers for esophageal squamous cell carcinoma (ESCC) 21 . Integrative analysis of miRNA-mRNA expression pro les post-esophageal brosis following ESD 22 ,and MicroRNA-21 as a potential biomarker for detecting esophageal carcinoma in Asian populations have been studied in a meta-analysis 23 .The downregulation of lncRNA LINC-PINT is implicated in the recurrence of esophageal squamous cell carcinoma, possibly interacting with miRNA-21 24 .…”

Non-coding RNA in tumor-infiltrating regulatory T cells formation and associated immunotherapy

“…MiR-146a expression in PBMCs was not only negatively correlated with Tregs but was also a marker of NSCLC liquid biopsy ( 130 ). The expression of miR-21 was associated with the inhibition of CD8 + T and was a potential diagnostic and prognostic marker for ESCC ( 131 ). The combined expression of miR-101, miR-548b, miR-554, and miR-1202 was a prognostic marker and potential therapeutic target for PCNSL ( 132 ).…”