Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C1864663 (
HCC
)
2,985
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Despite the success of monotherapies based on blockade of programmed cell death 1 (PD-1) in human melanoma, most patients do not experience durable clinical benefit. T-cell infiltration and/or the presence of PD-L1 in tumors may be used as indicators of clinical response; However, recent studies reported that preexisting tumor-specific T cells may have limited reinvigoration capacity. Therefore, evaluating status of T cells of tumor-adjacent area and its impact on the prognosis are very important. Here, we examined 117 surgical samples from
HCC
patients for infiltration of exhausted T cell (Tex) including CD4
+
-Tex, CD8
+
-Tex and regulatory T cell (
FOXP3
+
-Treg) in tumor and adjacent tissue. CD3
+
CD45RO
+
T cells were sorted from adjacent area or tumor core, then the clusters and heterogeneity of T cells were further interrogated by single-cell RNA sequencing. As a result, we suggested that abundance or location of T cell subsets is differentially correlate with long-term clinical outcome of
HCC
. In contrast with CD4
+
T or CD4
+
-Tex, the infiltration of CD8
+
T or CD8
+
-Tex cells was closely linked to overall or recurrence-free survival.
FOXP3
+
-Treg is more predictive of early recurrence. Single-cell transcriptional analysis demonstrates the composition of CD4
+
-Tex, CD8
+
-Tex, and
FOXP3
+
-Treg is shifted in tumor and adjacent tissue. Molecular profiles including genes coding checkpoint receptors, effector molecules are distinct between CD4
+
-Tex, CD8
+
-Tex, though some common features of CD4
+
and CD8
+
T cell exhaustion are revealed. In conclusion, we underline the heterogeneity and clinical relevance of Tex cells in
HCC
patients. A better understanding of Tex is critical for
HCC
monitoring and treatment.
...
PMID:Heterogeneity of exhausted T cells in the tumor microenvironment is linked to patient survival following resection in hepatocellular carcinoma. 3242 77
Exonuclease 1 (
EXO1
), a member of the RAD2 nuclease family, was first described as possessing 5' to 3' nuclease activity and 5' structure-specific endonuclease activity. Here, we show that
EXO1
is significantly upregulated in
HCC
tumor tissues and that high
EXO1
expression is significantly correlated with liver cirrhosis. We further demonstrate that
EXO1
knockdown decreases proliferation and colony forming abilities of
HCC
cells
in vitro
and tumorigenicity
in vivo
, as well as decreases migration and invasive capabilities of
HCC
cells. Alternatively,
EXO1
overexpression significantly increases the proliferation, colony forming ability, and migration and invasive capabilities of
HCC
cells
in vitro
. Additionally, we truncated a region upstream of the transcription start site (TSS) of
EXO1
and used the region with the strongest transcriptional activity to predict that the transcription factor
FOXP3
can bind to the
EXO1
promoter. Bioinformatics analysis found that
FOXP3
was positively correlated with
EXO1
and luciferase reporter assays and RT-PCR confirmed that
FOXP3
could enhance the transcriptional activity of
EXO1
. CCK-8 assays showed that depletion of
FOXP3
further reduces cell proliferation ability after knocking down of
EXO1 in vitro
. Taken together, our findings indicate that
EXO1
acts as an oncogene in
HCC
and its expression level is related to
FOXP3
activity.
...
PMID:
EXO1
Plays a Carcinogenic Role in Hepatocellular Carcinoma and is related to the regulation of
FOXP3
. 3262 39
