Stromal expression of cancer‑associated fibroblast‑related molecules, versican and lumican, is strongly associated with worse relapse‑free and overall survival times in patients with esophageal squamous cell carcinoma

Yamauchi, Naoto; Kanke, Yasuyuki; Saito, Katsuharu; Okayama, Hirokazu; Yamada, Shuhei; Nakajima, Shotaro; Endo, Eisei; Kase, Koji; Yamada, Leo; Nakano, Hiroshi; Matsumoto, Tomohiro; Hanayama, Hiroyuki; Watanabe, Yohei; Hayase, Suguru; Saze, Zenichiro; Mimura, Kosaku; Momma, Tomoyuki; Oki, Sadaaki; Hashimoto, Yuko; Kono, Koji

doi:10.3892/ol.2021.12706

Cited by 17 publications

(18 citation statements)

References 35 publications

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“…Previous studies showed that VCAN was closely associated with the proliferation and metastasis of various types of tumor cells, such as gastric cancer, leukaemia and breast cancer cells 40 – 42 . In addition, a recent study showed that stromal expression of VCAN was strongly associated with worse overall and relapse-free survival in patients with ESCC 43 . The ROC curves showed that all 9 hub genes had relatively high diagnostic value for ESCC patients.…”

Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics analysis of differentially expressed genes and immune cell infiltration characteristics in Esophageal Squamous cell carcinoma

Zuo

Liu

et al. 2021

Sci Rep

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Esophageal squamous cell carcinoma (ESCC) is a life-threatening thoracic tumor with a poor prognosis. The role of molecular alterations and the immune microenvironment in ESCC development has not been fully elucidated. The present study aimed to elucidate key candidate genes and immune cell infiltration characteristics in ESCC by integrated bioinformatics analysis. Nine gene expression datasets from the Gene Expression Omnibus (GEO) database were analysed to identify robust differentially expressed genes (DEGs) using the robust rank aggregation (RRA) algorithm. Functional enrichment analyses showed that the 152 robust DEGs are involved in multiple processes in the tumor microenvironment (TME). Immune cell infiltration analysis based on the 9 normalized GEO microarray datasets was conducted with the CIBERSORT algorithm. The changes in macrophages between ESCC and normal tissues were particularly obvious. In ESCC tissues, M0 and M1 macrophages were increased dramatically, while M2 macrophages were decreased. A robust DEG-based protein–protein interaction (PPI) network was used for hub gene selection with the CytoHubba plugin in Cytoscape. Nine hub genes (CDA, CXCL1, IGFBP3, MMP3, MMP11, PLAU, SERPINE1, SPP1 and VCAN) had high diagnostic efficiency for ESCC according to receiver operating characteristic (ROC) curve analysis. The expression of all hub genes except MMP3 and PLAU was significantly related to macrophage infiltration. Univariate and multivariate regression analyses showed that a 7-gene signature constructed from the robust DEGs was useful for predicting ESCC prognosis. Our results might facilitate the exploration of potential targeted TME therapies and prognostic evaluation in ESCC.

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Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics analysis of differentially expressed genes and immune cell infiltration characteristics in Esophageal Squamous cell carcinoma

Zuo

Liu

et al. 2021

Sci Rep

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“…Additional studies have demonstrated using VCAN-negative QRsP11 fibrosarcoma cells that VCAN is an important molecule in functional ECM and maintenance of cancer-associated fibroblasts (Fanhchaksai et al, 2016). In addition to this, the high expression levels of CAF-related molecules including VCAN, periostin, and lumican in the stroma of ESCC were significantly associated with worse recurrence-free survival (RFS) and overall survival in ESCC patients (Yamauchi et al, 2021). In addition, TGF-β enhances ovarian cancer cell invasiveness by up-regulating VCAN in CAFs.…”

Section: Discussionmentioning

confidence: 97%

Comprehensive Analysis of VCAN Expression Profiles and Prognostic Values in HCC

et al. 2022

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Background: Hepatocellular carcinoma (HCC) is the world’s most common cause of cancer death. Therefore, more molecular mechanisms need to be clarified to meet the urgent need to develop new detection and treatment strategies.Methods: We used TCGAportal, Kaplan–Meier Plotter, the Cistrome DB Toolkit Database, MExpress, GEPIA2, and other databases to discuss the expression profiles, possible biological function, and potential prognostic value of versican (VCAN) in HCC. We conducted cell experiments such as Transwell migration and invasion assays, wound healing assay, and CCK8 experiment to explore the function of VCAN in HCC.Result: We selected three HCC transcriptome databases GSE124535, GSE136247, and GSE144269 and analyzed the overexpressed genes contained in them. The overlapping genes were found by the Venn map, and two interacting network modules were found by Mcode. Module 1 was mainly related to mitosis and cell cycle, and module 2 was mainly related to EMT, angiogenesis, glycolysis, and so on. We found that the seed gene in module 2 is VCAN. Data from TCGAportal showed that compared with normal tissues, the expression of VCAN was up-regulated in HCC tissues. The patients with high expression of VCAN had shorter distant recurrence-free survival and overall survival. Multiple possible VCAN interactions had also been identified. These results revealed that the level of VCAN was higher in the subtypes of HCC with higher malignant degree and was connected to the poor prognosis. In addition, the treatment of VCAN with DNA methyltransferase inhibitors and transcription factor inhibitors may improve the prognosis of patients with HCC.Conclusion: Our findings systematically elucidated the expression profile and different prognostic values of VCAN in HCC, which may provide new therapeutic targets and potential prognostic biomarkers for HCC patients.

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“…In the present study, high stromal periostin expression was significantly associated with high budding in UTUCs. Several studies have also indicated a close relationship between stromal periostin overexpression and histological small clustering and/or isolated invasive patterns of cancer cells at the tumor front, such as tumor budding in colorectal adenocarcinoma [ 35 ] and “pattern of invasion” in oral squamous cell carcinoma [ 36 ]. Overexpression of periostin co-localizes with fibronectin and collagen, thereby promoting an extracellular matrix organization through the activation of focal adhesion kinase and PI3K/Akt signaling [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic impact of stromal periostin expression in upper urinary tract urothelial carcinoma

et al. 2022

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Background Periostin is an extracellular matrix protein that has been known to be implicated in fibrillogenesis and cell migration, including cancer metastasis. Periostin overexpression in cancer cells and/or intervening stroma is usually related to tumor progression and poor patient outcomes in various human cancers; however, its role in urothelial carcinoma, especially upper urinary tract urothelial carcinomas (UTUCs), remains inconclusive. Methods Samples from 126 consecutive cases of invasive UTUC (69 renal pelvic cancers and 57 ureteral cancers) were histologically reviewed and analyzed for periostin expression using immunohistochemistry. The intensities of immunoreactivity and the fraction of positive cancer cells and stroma (i.e., epithelial and stromal expression, respectively) were classified into four categories each (intensity, 0–3; fraction, 0–25% = 1; 26–50% = 2; 51–75% = 3; and > 75% = 4). The overall score was determined by multiplying both scores, and overall scores ≥ 6 were considered to indicate high periostin expression. Results Among 126 UTUCs, 55 (44%; 27 renal pelvic and 28 ureteral cancers) showed high stromal periostin expression. None of the cases were considered to have high epithelial periostin expression. High stromal periostin expression was associated with non-papillary gross findings, higher pathological T category, lymphovascular invasion, concomitant carcinoma in situ, subtype histology, lymph node metastasis, positive surgical margins, high tumor budding, and high tumor-associated immune cell status. Multivariate analysis revealed that high stromal periostin expression was an independent predictor of overall survival (p = 0.00072, hazard ratio = 3.62), and lymphovascular invasion and high stromal periostin expression were independent predictors of cancer-specific survival (p = 0.032 and 0.020, hazard ratio = 2.61 and 3.07, respectively). Conclusions Stromal periostin expression was often observed in invasive UTUCs with adverse clinicopathological factors and may be a useful predictor of patient outcomes.

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Stromal expression of cancer‑associated fibroblast‑related molecules, versican and lumican, is strongly associated with worse relapse‑free and overall survival times in patients with esophageal squamous cell carcinoma

Cited by 17 publications

References 35 publications

Integrated bioinformatics analysis of differentially expressed genes and immune cell infiltration characteristics in Esophageal Squamous cell carcinoma

Integrated bioinformatics analysis of differentially expressed genes and immune cell infiltration characteristics in Esophageal Squamous cell carcinoma

Comprehensive Analysis of VCAN Expression Profiles and Prognostic Values in HCC

Prognostic impact of stromal periostin expression in upper urinary tract urothelial carcinoma

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