CD90 expression in human intrahepatic cholangiocarcinoma is associated with lymph node metastasis and poor prognosis

Yamaoka, Ryoya; Ishii, Takamichi; Kawai, Takayuki; Yasuchika, Kentaro; Miyauchi, Yuya; Kojima, Hidenobu; Katayama, Hokahiro; Ogiso, Satoshi; Fukumitsu, Ken; Üemoto, Shinji

doi:10.1002/jso.25192

Cited by 20 publications

(20 citation statements)

References 29 publications

(27 reference statements)

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“…Treatment of CCA depends on the anatomical location, but there are some surgical concerns remain further verification, including the use of lymph node dissection, liver transplantation, adjuvant chemotherapy, and target therapies (17)(18)(19)(20). In most surgery centers, lymph node metastasis is considered a contraindication for surgical options, but it is considered resectable when it is limited to be regional in partial hospitals (21,22). In the present study, lymph node metastasis was found to be an independent prognostic factor for both OS and TS in iCCA and hiCCA, but not in dCCA.…”

Section: Discussionsupporting

confidence: 44%

Cholangiocarcinoma: anatomical location-dependent clinical, prognostic, and genetic disparities

Hang¹,

Jeong²,

Meng³

et al. 2019

Ann Transl Med

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Background: Anatomical location is considered in diagnostic and therapeutic approaches of cholangiocarcinoma (CCA). However, disparities and its extents in proportion of surgical candidates, prognostic factors, prognostic genetic networks, susceptibility for lymph node dissection, and disease stage at diagnosis remain to be confirmed. Methods: A total of 11,710 patients with cholangiocarcinoma from Surveillance, Epidemiology, and End Results Cancer Registries (SEER) and 45 CCA patients with paired tumor and normal specimens from The Cancer Genome Atlas were studied. Kaplan-Meier estimation, Cox proportional hazards regression, Pearson's correlation, comparison between anatomical location (distal, intrahepatic, and perihilar)-dependent CCAs, differential expressive gene stratification, potential interactive gene identification, and confirmation on pathways of the prognostic networks were carried out.Results: Survival outcomes were most favorable in the distal type, followed by perihilar and intrahepatic types, but postsurgical prognosis was slightly higher in intrahepatic type compared to perihilar type. Distant historic stage at diagnosis was noticed in intrahepatic type. Significant prognostic factors and their hazards ratios were dependent to the anatomical location. In addition, lymph node dissection provided significant survival benefits in perihilar type only. Furthermore, prognosis-predictive genes, as well as potential processes and pathways, were significantly among the anatomical location-dependent types that the genes barely overlapped.Conclusions: There are disparities in almost all aspects among distal, intrahepatic, and perihilar CCAs.Anatomical location needs to be considered in treatment, prognostic estimation, identifying targets, and developing therapeutic approaches for CCA.

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Section: Discussionsupporting

confidence: 44%

Cholangiocarcinoma: anatomical location-dependent clinical, prognostic, and genetic disparities

Hang¹,

Jeong²,

Meng³

et al. 2019

Ann Transl Med

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“…Stromal PDGFRa was found to decrease with tumor progression [33][34][35] , while a high expression of stromal PDGFRb was associated with a worse prognosis in different solid tumors [36][37][38][39][40][41][42] and drug resistance 43 . Likewise, CD90 defined fibroblasts were adversely associated with clinical outcome 44,45 but were also discussed as immune-regulatory fibroblasts [46][47][48] .…”

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confidence: 99%

Fibroblasts in urothelial bladder cancer define stroma phenotypes that are associated with clinical outcome

Mezheyeuski

Segersten

Leiss

et al. 2020

Sci Rep

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Little attention was given to the interaction between tumor and stromal cells in urothelial bladder carcinoma (UBC). While recent studies point towards the existence of different fibroblast subsets, no comprehensive analyses linking different fibroblast markers to UBC patient survival have been performed so far. Through immunohistochemical analysis of five selected fibroblast markers, namely alpha smooth muscle actin (ASMA), CD90/Thy-1, fibroblast activation protein (FAP), platelet derived growth factor receptor-alpha and-beta (PDGFRa,-b), this study investigates their association with survival and histopathological characteristics in a cohort of 344 UBC patients, involving both, muscleinvasive and non-muscle-invasive cases. The data indicates that combinations of stromal markers are more suited to identify prognostic patient subgroups than single marker analysis. Refined stromamarker-based patient stratification was achieved through cluster analysis and identified a FAPdominant patient cluster as independent marker for shorter 5-year-survival (HR(95% CI)2.25(1.08-4.67), p = 0.030). Analyses of interactions between fibroblast and CD8a-status identified a potential minority of cases with CD90-defined stroma and high CD8a infiltration showing a good prognosis of more than 80% 5-year-survival. Presented analyses point towards the existence of different stroma-cell subgroups with distinct tumor-modulatory properties and motivate further studies aiming to better understand the molecular tumor-stroma crosstalk in UBC. The estimated incidence of urinary bladder cancer (UBC) worldwide was about 550.000 new cases and 200.000 deaths in 2018 1 , with highest incidences indicated in developed areas 2. Given that the prevalence of UBC is several times higher than the incidence, it represents a major burden for health care systems. Carcinomas originating from the urothelium, the inner surface of the bladder, represent the most common type of bladder cancer 3,4. Approximately 70% of all newly diagnosed cases are classified as non-muscle-invasive bladder cancer disease, while about 30% of patients have already muscle-invasive tumors with 10-15% of them being metastatic 5-8. Reported 5-year recurrence rates of non-muscle invasive cases range between 40-70% among the highest recurrence rates of solid tumors 3,9. Multidisciplinary approaches have been established in order to improve patient management and to decrease the mortality rate, but still treatment strategies for UBC remain controversial. A better understanding of the mechanisms underlying tumor progression is crucial and novel prognostic and predictive markers as well as therapeutic targets need to be identified 10,11. Recent research efforts on UBC aimed mostly to decipher molecular drivers of an invasive tumor phenotype through description of genetic varieties, and with the introduction of checkpoint inhibitory immunotherapy, awareness has also risen for tumor infiltrating leukocytes 12,13. However, little attention was given the interaction of tumor cells and non-leukoc...

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“…The methylation of DLEC1 cilia and flagella associated protein is engaged in a favorable clinical outcome and prognosis in patients with small duct ICC [6]. However, CD90 expression contributed to lymph node metastasis and thereby leads to a poor prognosis in patients with ICC [7]. The expression of VEGFR-3 in ICC also promotes the angiogenesis of lymph, thereby resulting in an unfavorable prognosis [8].…”

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confidence: 99%

Identification of prognostic factors for intrahepatic cholangiocarcinoma using long non-coding RNAs-associated ceRNA network

et al. 2020

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Background: Accumulating amount of evidence has highlighted the important roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in tumor pathogenesis. However, the roles of long non coding RNAs (lncRNAs) in the lncRNA-related ceRNA network of intrahepatic cholangiocarcinoma (ICC) still remain enigmatic. The current study aims to identify prognostic factors in the lncRNA-related ceRNA network of ICC. Methods: The transcriptome sequencing data of lncRNAs, messenger RNA (mRNA) and microRNA (miR) were downloaded from the SRA and TCGA databases. Differentially expressed lncRNAs (DElncRNAs), DEmiRs and DEmRNAs were identified and adopted to construct an lncRNA-miR-mRNA ceRNA network. ICC-associated DEmRNAs were adopted to construct the protein-protein interaction (PPI) network. The expression of the top 6 genes in the hub module was validated with mRNA transcriptome sequencing data and ICC-related gene expression dataset GSE45001, followed by GO and KEGG pathway enrichment analysis. The relationship between the hub gene-associated ceRNA network and the overall survival of patients with ICC was predicted by conducting a Kaplan-Meier survival analysis. Results: Sixty co-expressed DEmRNAs were identified in the ceRNA network. The top 6 hub genes consisted of downregulated FOS, IGF2, FOXO1 and NTF3, upregulated IGF1R, and insignificantly downregulated HGF in ICC tissues, when compared to that of normal adjacent tissues, followed by the successful construction of lncRNA-miR-hub network consisting of 86 ceRNA modules. MME-AS1 and hsa-miR-182 were associated with overall survival in ICC patients. FOS, IGF1R, IGF2, FOXO1, and NTF3 might target "TGF-β signaling pathway", "the hedgehog signaling pathway", "retinol metabolism", or "type II diabetes mellitus" pathways respectively. Conclusion: These results indicate that FOS, IGF1R, IGF2, FOXO1, and NTF3 were useful prognostic factors in determining the prognosis of patients with ICC.

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CD90 expression in human intrahepatic cholangiocarcinoma is associated with lymph node metastasis and poor prognosis

Abstract: CD90 cells demonstrate high metastatic potential owing to Wnt/β-catenin signaling activation and are associated with poor prognosis in ICC.

Cited by 20 publications

References 29 publications

Cholangiocarcinoma: anatomical location-dependent clinical, prognostic, and genetic disparities

Cholangiocarcinoma: anatomical location-dependent clinical, prognostic, and genetic disparities

Fibroblasts in urothelial bladder cancer define stroma phenotypes that are associated with clinical outcome

Identification of prognostic factors for intrahepatic cholangiocarcinoma using long non-coding RNAs-associated ceRNA network

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