FABP6 Expression Correlates with Immune Infiltration and Immunogenicity in Colorectal Cancer Cells

Lian, Wenping; Wang, Zhongquan; Ma, Yajie; Tong, Yalin; Zhang, Xinyu; Jin, Huifang; Zhao, Shuai; Yu, Ruijing; Ju, Shaotan; Zhang, Xinyun; Guo, Xiao‐Na; Huang, Tao; Ding, Xianfei; Peng, Mengle

doi:10.1155/2022/3129765

Cited by 8 publications

(4 citation statements)

References 34 publications

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“…One striking expression difference was based on the greater initial expression seen with gastrotropin (Fabp6; involved binding of long-chain fatty acids and bile acids). The expression of Fabp6 and other genes in its family has been found to be associated with colorectal cancer, and its expression is strongly correlated with cell migration and the immune response [56][57][58].…”

Section: Discussionmentioning

confidence: 99%

Proteins Involved in Focal Cell Adhesion and Podosome Formation Are Differentially Expressed during Colorectal Tumorigenesis in AOM-Treated Rats

Swain,

Kresak

2024

Cancers

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Colorectal tumorigenesis involves the development of aberrant crypt foci (ACF) or preneoplastic lesions, representing the earliest morphological lesion visible in colon cancer. The purpose of this study was to determine changes in protein expression in carcinogen-induced ACF as they mature and transform into adenomas. Protein expression profiles of azoxymethane (AOM)-induced F344 rat colon ACF and adenomas were compared at four time points, 4 (control), 8, 16, and 24 weeks post AOM administration (n = 9/group), with time points correlating with induction and transformation events. At each time point, micro-dissected ACF and/or adenoma tissues were analyzed across multiple quantitative two-dimensional (2D-DIGE) gels using a Cy-dye labeling technique and a pooled internal standard to quantify expression changes with statistical confidence. Western blot and subsequent network pathway mapping were used to confirm and elucidate differentially expressed (p ≤ 0.05) proteins, including changes in vinculin (Vcl; p = 0.007), scinderin (Scin; p = 0.02), and profilin (Pfn1; p = 0.01), By determining protein expression changes in ACF as they mature and transform into adenomas, a “baseline” of altered regulatory proteins associated with adenocarcinoma development in this model has been elucidated. These data will enable future studies aimed at biomarker identification and understanding the molecular biology of intestinal tumorigenesis and adenocarcinoma maturation under varying intestinal conditions.

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Section: Discussionmentioning

confidence: 99%

Proteins Involved in Focal Cell Adhesion and Podosome Formation Are Differentially Expressed during Colorectal Tumorigenesis in AOM-Treated Rats

Swain,

Kresak

2024

Cancers

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“…This gene panel could not only efficiently discriminate between these immune subtypes, but also serve as robust biomarkers for the identification of immune subtypes. The expression of these genes has been reported to be associated with different immune related functions in various cancers [38][39][40][41][42] and some are also used as biomarkers for predicting the efficacy of immunotherapy in various cancers [43][44][45]. Apart from imparting immune functions, the above-mentioned genes are also known to be involved in tumorigenesis of several cancers [39,44,[46][47][48][49][50][51][52][53][54][55], including CaCx [56][57][58].…”

Section: Discussionmentioning

confidence: 99%

Identification of HPV16 positive cervical cancer subsets characterized by divergent immune and oncogenic phenotypes with potential implications for immunotherapy

Ghosh

Sinha

et al. 2023

TUB

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BACKGROUND: Cervical cancers (CaCx), like many other cancer types, portray high molecular heterogeneity that affects response to therapy, including immunotherapy. In India and other developing countries, CaCx mortality rates are very high because women report to the clinics with advanced cancers in absence of organized screening programs. This calls for implementation of newer therapeutic regimens for CaCx, like immunotherapy, which is again not used commonly in such countries. OBJECTIVE: Therefore, we focused on dissecting tumour immune heterogeneity, if any, identify immune gene-based biomarkers of heterogeneity and subsets of such cancers with the potential for immunotherapy. We also attempted to characterize the cancer-associated phenotypes of such subsets, including viral load, to decipher the relationship of tumour immunogenicity with oncogenicity. METHODS: Employing RNA-seq analysis of 44 HPV16 positive CaCx patients, immune subtypes were identified by unsupervised hierarchical clustering of global immune-gene expression profiles. Proportions of tumor infiltrating immune cells in the tumor milieu were estimated, employing Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT), using gene expression data from RNA-seq. The oncogenic phenotypes of the immune subtypes of CaCx were deciphered through differential gene expression (DEGs) and pathway enrichment analysis. Viral load was estimated through TaqMan-based qRT-PCR analysis. RESULTS: Analysis revealed the presence of two immune subtypes of CaCx, A (26/44; 59.09%) and B (18/44; 40.90%). Compared to Subtype-A, Subtype-B portrayed overexpression of immune genes and high infiltration of immune cells, specifically CD8+ T cells (p < 0.0001). Besides, a significant correlation between PD-1 and PD-L1 co-expression among Subtype-B, as opposed to Subtype-A, confirmed the interactive roles of these immune checkpoint molecules in Subtype B. Stepwise discriminant analysis pin-pointed ten immune-genes that could classify 100% of the patients significantly (p < 0.0001) into the two immune subtypes and serve as potential biomarkers of CaCx immunity. Differential gene expression analysis between the subtypes unveiled that Subtype-B was more biologically aggressive than Subtype-A, reflecting loss of structural integrity and promotion of cancer progression. The viral load was significantly lower in Subtype-B (average viral load = 10.74/100 ng of genomic DNA) compared to Subtype-A (average viral load = 14.29/100 ng of genomic DNA). Thus viral load and the ten-gene panel underscore their association with immunogenicity and oncogenicity. CONCLUSION: Our study provides strong evidence that only a subset, about 41% of HPV16 positive CaCx patients in India, portray immune enrichment of the tumor milieu coupled with aggressive phenotypes. Such subtypes are therefore likely to benefit through checkpoint molecule-based or tumor infiltrating lymphocyte-based immunotherapy, which could be a leap forward in tackling aggressive forms of such CaCx in India and other developing countries.

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“…Recent studies have begun to unveil its potential role in cancer pathogenesis. Lian W et al [11] pinpointed FABP6 as a candidate for enhancing immunotherapy in colorectal cancer, owing to its impact on immune infiltration, upregulation of major histocompatibility complex (MHC) class I expression, and recruitment of CD8 + T cells. Another investigation reported elevated FABP6 levels in primary colorectal cancer and adenomas, but a significant reduction in lymph node metastases, implicating its dual role in early carcinogenesis and modulation of tumor attributes such as aggressiveness, proliferation, and apoptosis [12].…”

Section: Introductionmentioning

confidence: 99%

REST Promotes Autophagy in Gastric Cancer by Transcriptionally Activating FABP6 to Inhibit the Akt/mTOR Signaling Pathway

Luo,

Yu,

Yuan

et al. 2024

Front. Biosci. (Landmark Ed)

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Background: Gastric cancer (GC) is a leading cause of cancer-associated death worldwide. Its molecular mechanisms, especially concerning autophagy and various signaling pathways, are not fully understood. Fatty Acid Binding Protein 6 (FABP6) and RE1 Silencing Transcription Factor (REST) emerge as potential key players in this context. This study sought to analyze the functional relationship of FABP6 and REST concerning autophagy and their implications on the Akt/mTOR signaling pathway within GC cells. Methods: A comprehensive bioinformatics approach was used to identify key prognostic markers in GC. The effects of FABP6 and REST on autophagy along with Akt/mTOR signaling pathways were analyzed by techniques including Western blotting (WB), flow cytometry, Transwell assay, dual luciferase reporter assay, and others. Results: FABP6 was identified as overexpressed in GC, linked with poor prognosis. FABP6 silencing reduces GC cell proliferation, induces S- and G2-phase arrest, and downregulates cyclins CDK2 and CDK4. It also inhibited GC cell invasion/migration and autophagy, effects that were counteracted by MG132. When combined with PI3K inhibitor LY294002c, FABP6 knockdown showed synergistic anti-proliferative effects, modulating the Akt/mTOR pathway. Besides, the transcription factor REST has been shown to directly regulate FABP6 expression, affecting autophagy and the Akt/mTOR signaling pathway in a FABP6-dependent manner. Conclusions: REST positively regulates autophagy and negatively affects the Akt/mTOR signaling pathway in GC cells in a FABP6-dependent manner, providing valuable insights into regulatory networks involving FABP6 and REST.

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FABP6 Expression Correlates with Immune Infiltration and Immunogenicity in Colorectal Cancer Cells

Cited by 8 publications

References 34 publications

Proteins Involved in Focal Cell Adhesion and Podosome Formation Are Differentially Expressed during Colorectal Tumorigenesis in AOM-Treated Rats

Proteins Involved in Focal Cell Adhesion and Podosome Formation Are Differentially Expressed during Colorectal Tumorigenesis in AOM-Treated Rats

Identification of HPV16 positive cervical cancer subsets characterized by divergent immune and oncogenic phenotypes with potential implications for immunotherapy

REST Promotes Autophagy in Gastric Cancer by Transcriptionally Activating FABP6 to Inhibit the Akt/mTOR Signaling Pathway

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