Index of Cancer-Associated Fibroblasts Is Superior to the Epithelial–Mesenchymal Transition Score in Prognosis Prediction

Ko, Ying Chieh; Lai, Ting Yu; Hsu, Shih-Hsin; Wang, Fu Hui; Su, Sheng; Chen, Yu Lian; Tsai, Min-Lung; Wu, Chia‐Huei; Hsiao, Jenn Ren; Chang, Jang Yang; Robinson, Dan R.; Lin, Chung Yen; Lin, Shankung

doi:10.3390/cancers12071718

Cited by 23 publications

(26 citation statements)

References 54 publications

(80 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, we demonstrated that TW2.6, but not OC3 or OEC-M1, displayed p-EMT multicellular characteristics in vitro and in vivo (10). In addition, mesenchymal OC3 repeatedly grew slower and smaller than its p-EMT TW2.6 counterpart in vivo [Figure 1C and ref (11)], a phenomenon consistent with one prior study in that head and neck cancer tissues of the inflammatory mesenchymal subtype had a better prognosis (24).…”

Section: Higher Microvessel Density Was Detected In the Mouse Stroma Of The P-emt Tw26 Tumorssupporting

confidence: 90%

“…In addition, inhibition of DDR1 kinase activity in p-EMT oral cancer cells (TW2.6) disrupted cell cohesiveness in a 2D culture, reduced spheroid invasion in a collagen gel matrix, and suppressed angiolymphatic invasion in xenograft tissues (10). It is worth noting that compared to a mesenchymal subtype (OC3) that has a similar growth rate and clonogenicity in vitro, p-EMT TW2.6 repeatedly grew faster (e.g., 32 vs. 81 days to reach 500 mm 3 ) in immunodeficient mice (NOG) despite their tumor-bearing rates were similar (11).…”

Section: Introductionmentioning

confidence: 99%

“…It is worth noting that compared to a mesenchymal subtype (OC3) that has a similar growth rate and clonogenicity in vitro , p-EMT TW2.6 repeatedly grew faster (e.g., 32 vs . 81 days to reach 500 mm 3 ) in immunodeficient mice (NOG) despite their tumor-bearing rates were similar ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

“…Along the same vein, our prior results showed that the stroma of mesenchymal OC3 tumors harbored a statistically higher extent of mouse fibroblasts than p-EMT TW2.6 tumors. By translating the most significantly expressed gene matrix into clinical datasets of oral cancer tissues, we showed that the summed expression of FN1 , TGFB2 , TGFBR2 , and TGFBI , dubbed the CAF index, is a poor indicator of overall survival for oral cancer (n=40) and the PANCAN (n=9,356) cohorts ( 11 ). Here, we continued to investigate the molecular interactions between tumor cells and stromal components in p-EMT TW2.6 tumors.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Identification of Prognostic Biomarkers Originating From the Tumor Stroma of Betel Quid-Associated Oral Cancer Tissues

et al. 2021

Self Cite

View full text Add to dashboard Cite

BackgroundPartial epithelial-mesenchymal transition (p-EMT) is a distinct clinicopathological feature prevalent in oral cavity tumors of The Cancer Genome Atlas. Located at the invasion front, p-EMT cells require additional support from the tumor stroma for collective cell migration, including track clearing, extracellular matrix remodeling and immune evasion. The pathological roles of otherwise nonmalignant cancer-associated fibroblasts (CAFs) in cancer progression are emerging.MethodsGene set enrichment analysis was used to reveal differentially enriched genes and molecular pathways in OC3 and TW2.6 xenograft tissues, representing mesenchymal and p-EMT tumors, respectively. R packages of genomic data science were executed for statistical evaluations and data visualization. Immunohistochemistry and Alcian blue staining were conducted to validate the bioinformatic results. Univariate and multivariate Cox proportional hazards models were performed to identify covariates significantly associated with overall survival in clinical datasets. Kaplan–Meier curves of estimated overall survival were compared for statistical difference using the log-rank test.ResultsCompared to mesenchymal OC3 cells, tumor stroma derived from p-EMT TW2.6 cells was significantly enriched in microvessel density, tumor-excluded macrophages, inflammatory CAFs, and extracellular hyaluronan deposition. By translating these results to clinical transcriptomic datasets of oral cancer specimens, including the Puram single-cell RNA-seq cohort comprising ~6000 cells, we identified the expression of stromal TGFBI and HYAL1 as independent poor and protective biomarkers, respectively, for 40 Taiwanese oral cancer tissues that were all derived from betel quid users. In The Cancer Genome Atlas, TGFBI was a poor marker not only for head and neck cancer but also for additional six cancer types and HYAL1 was a good indicator for four tumor cohorts, suggesting common stromal effects existing in different cancer types.ConclusionsAs the tumor stroma coevolves with cancer progression, the cellular origins of molecular markers identified from conventional whole tissue mRNA-based analyses should be cautiously interpreted. By incorporating disease-matched xenograft tissue and single-cell RNA-seq results, we suggested that TGFBI and HYAL1, primarily expressed by stromal CAFs and endothelial cells, respectively, could serve as robust prognostic biomarkers for oral cancer control.

show abstract

Section: Higher Microvessel Density Was Detected In the Mouse Stroma Of The P-emt Tw26 Tumorssupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Identification of Prognostic Biomarkers Originating From the Tumor Stroma of Betel Quid-Associated Oral Cancer Tissues

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…In this study, TGFBI expression was an indicator of the level of infiltration of CAFs, which represent the main component of the tumor stroma and are strongly associated with epithelial–mesenchymal transition, massive stromal cell infiltration, and poor cancer prognosis. CAF infiltration can be used to predict survival in patients with oral squamous cell carcinoma ( Ko et al, 2020 ). Tumor-associated macrophages promote OV cell migration, adhesion, and invasion by secreting TGFBI, and they have been associated with short PFS in high-grade serous OV patients ( Steitz et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Pan-Cancer Analysis of the Associations of TGFBI Expression With Prognosis and Immune Characteristics

Chen

Han

Feng

et al. 2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

Transforming growth factor-beta-induced (TGFBI) protein has important roles in tumor growth, metastasis, and immunity. However, there is currently no pan-cancer evidence regarding TGFBI. In this study, we conducted a pan-cancer analysis of TGFBI mRNA and protein expression and prognoses of various cancer types using public databases. We also investigated the associations of TGFBI expression with tumor microenvironment (TME) components, immune cell infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI), along with the TGFBI genetic alteration types. The results showed that TGFBI expression varied among different cancer types, and it was positively or negatively related to prognosis in various cancers. TGFBI expression was also significantly correlated with TME components, TMB, MSI, immune cell infiltration, and immunoinhibitory and immunostimulatory gene subsets. These findings indicate that TGFBI participates in various immune responses and it may function as a prognostic marker in various cancers. The findings may be useful for developing immunotherapies that target TGFBI.

show abstract

Effect of cancer‐associated fibroblasts on prognosis and immune infiltration in head and neck squamous cell carcinoma

Xu,

Zhu,

Zong

et al. 2024

Precision Medical Sciences

View full text Add to dashboard Cite

Cancer‐associated fibroblasts (CAFs) are the center of cross‐communication between various cells in the tumor stroma. However, how CAFs‐associated genes play an important role in Head and neck squamous cell carcinoma (HNSCC) prognosis has not been reported. Transcriptome data were downloaded from TCGA and GEO databases. Devtools, DPIC, xCell, MCPcounter, and Estimate packages were used to calculate CAFs scores and immune infiltration. Prognosis and weighted gene coexpression network analysis (WGCNA) analysis were performed between high or low risk populations based on CAF scores. Hub genes were identified, intersected, and enriched between TCGA and GEO databases. CAFs related genes were used to construct a prognostic model and the tumor immune dysfunction and exclusion database was used to evaluate the immune infiltration. Drug sensitivity, difference analysis and the HPA database were used to identify sensitive drugs and verify their expression. TCGA and GEO data suggested that CAFs scores had a role in HNSCC prognosis prediction. Based on CAFs scores, WGCNA and core gene enrichment analysis were performed to construct a CAFs‐related prognostic model. The prognostic model composed of a total of 12 CAFs genes could predict the prognosis well and was validated in the validation dataset, demonstrating its applicability to external data. According to the model, although there was no statistical difference in immune escape between the high and low risk groups, the proportion of patients who responded to immunotherapy was different. Drug sensitivity also differed between the two groups. This study suggests that CAFs associated genetic signatures may help to optimize risk stratification and provide new insights into individualized cancer treatment.

show abstract

Index of Cancer-Associated Fibroblasts Is Superior to the Epithelial–Mesenchymal Transition Score in Prognosis Prediction

Cited by 23 publications

References 54 publications

Identification of Prognostic Biomarkers Originating From the Tumor Stroma of Betel Quid-Associated Oral Cancer Tissues

Identification of Prognostic Biomarkers Originating From the Tumor Stroma of Betel Quid-Associated Oral Cancer Tissues

Pan-Cancer Analysis of the Associations of TGFBI Expression With Prognosis and Immune Characteristics

Effect of cancer‐associated fibroblasts on prognosis and immune infiltration in head and neck squamous cell carcinoma

Contact Info

Product

Resources

About