IFN-γ affects pancreatic cancer properties by MACC1-AS1/MACC1 axis via AKT/mTOR signaling pathway

Xy, Shi; Xl, Zhang; Shi, Qing; Qiu, Xiaoqiang; Wu, Xiaolian; Zheng, B-L; Jiang, Haixing; Qin, Shanyu

doi:10.1007/s12094-021-02748-w

Cited by 4 publications

(3 citation statements)

References 60 publications

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“…Our results suggested that the C2 subtype with high IFN-γ scores had a significantly better prognosis than C1, suggesting that the IFN-γ pathway may play an anti-cancer role in PC. This conclusion is consistent with previous studies ( 11 , 36 , 37 ), indicating that IFN-γ could inhibit the development of pancreatic cells and may be considered a therapy target for PC patients in the future. And in comparison to the C1 subgroup, the C2 subgroup demonstrates increased expression of IFN-γGs, including HLA-DPB1, HLA-DPA1, HLA-DBQ1, IRF4, IRF8, and JAK2, while exhibiting decreased expression of GBP3.…”

Section: Discussionsupporting

confidence: 93%

Identification and characterization of interferon-γ signaling-based personalized heterogeneity and therapeutic strategies in patients with pancreatic cancer

Chen,

Yuan,

Guan

et al. 2023

Front. Oncol.

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BackgroundInterferon-γ (IFN-γ) is a key cytokine with diverse biological functions, including antiviral defense, antitumor activity, immune regulation, and modulation of cellular processes. Nonetheless, its role in pancreatic cancer (PC) therapy remains debated. Therefore, it is worthwhile to explore the role of Interferon-γ related genes (IFN-γGs) in the progression of PC development.MethodologyTranscriptomic data from 930 PC were sourced from TCGA, GEO, ICGC, and ArrayExpress, and 93 IFN-γGs were obtained from the MSigDB. We researched the characteristics of IFN-γGs in pan-cancer. Subsequently, the cohort of 930 PC was stratified into two distinct subgroups using the NMF algorithm. We then examined disparities in the activation of cancer-associated pathways within these subpopulations through GSVA analysis. We scrutinized immune infiltration in both subsets and probed classical molecular target drug sensitivity variations. Finally, we devised and validated a novel IFN-γ related prediction model using LASSO and Cox regression analyses. Furthermore, we conducted RT-qPCR and immunohistochemistry assays to validate the expression of seven target genes included in the prediction model.ResultsWe demonstrated the CNV, SNV, methylation, expression levels, and prognostic characteristics of IFN-γGs in pan-cancers. Notably, Cluster 2 demonstrated superior prognostic outcomes and heightened immune cell infiltration compared to Clusters 1. We also assessed the IC50 values of classical molecular targeted drugs to establish links between IFN-γGs expression levels and drug responsiveness. Additionally, by applying our prediction model, we segregated PC patients into high-risk and low-risk groups, identifying potential benefits of cisplatin, docetaxel, pazopanib, midostaurin, epothilone.B, thapsigargin, bryostatin.1, and AICAR for high-risk PC patients, and metformin, roscovitine, salubrinal, and cyclopamine for those in the low-risk group. The expression levels of these model genes were further verified through HPA website data and qRT-PCR assays in PC cell lines and tissues.ConclusionThis study unveils IFN-γGs related molecular subsets in pancreatic cancer for the first time, shedding light on the pivotal role of IFN-γGs in the progression of PC. Furthermore, we establish an IFN-γGs related prognostic model for predicting the survival of PC, offering a theoretical foundation for exploring the precise mechanisms of IFN-γGs in PC.

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Section: Discussionsupporting

confidence: 93%

Identification and characterization of interferon-γ signaling-based personalized heterogeneity and therapeutic strategies in patients with pancreatic cancer

Chen,

Yuan,

Guan

et al. 2023

Front. Oncol.

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“…In lung cancer [ 43 ] and ovarian cancer [ 39 ], overexpressing MACC1 has been demonstrated to overcome chemotherapeutic resistance, and down-regulating MACC1 expression has been found to increase the sensitivity of cisplatin-resistant cancer cells to the drug [ 44 ]. MACC1′s involvement in the AKT signaling pathway has also been found in nasopharyngeal carcinoma [ 45 ], colon cancer [ 46 ], pancreatic cancer [ 47 ], and human glioblastoma [ 48 ]. The biological role of MACC1 in malignant tumors is related to the state of the Akt signaling pathway.…”

Section: Macc1mentioning

confidence: 99%

MACC1 as a Potential Target for the Treatment and Prevention of Breast Cancer

Jiao

Yang

et al. 2023

Biology

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Metastasis associated in colon cancer 1 (MACC1) is an oncogene first identified in colon cancer. MACC1 has been identified in more than 20 different types of solid cancers. It is a key prognostic biomarker in clinical practice and is involved in recurrence, metastasis, and survival in many types of human cancers. MACC1 is significantly associated with the primary tumor, lymph node metastasis, distant metastasis classification, and clinical staging in patients with breast cancer (BC), and MACC1 overexpression is associated with reduced recurrence-free survival (RFS) and worse overall survival (OS) in patients. In addition, MACC1 is involved in BC progression in multiple ways. MACC1 promotes the immune escape of BC cells by affecting the infiltration of immune cells in the tumor microenvironment. Since the FGD5AS1/miR-497/MACC1 axis inhibits the apoptotic pathway in radiation-resistant BC tissues and cell lines, the MACC1 gene may play an important role in BC resistance to radiation. Since MACC1 is involved in numerous biological processes inside and outside BC cells, it is a key player in the tumor microenvironment. Focusing on MACC1, this article briefly discusses its biological effects, emphasizes its molecular mechanisms and pathways of action, and describes its use in the treatment and prevention of breast cancer.

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“…IL-12 is an acute inflammatory factor that could inhibit tumor progression in gastrointestinal tumors, and its high expression leads to a longer survival time[ 12 ]. Additionally, the interferon family is a potential therapeutic biomarker, which could inhibit the occurrence and progression of gastrointestinal tumors by regulating cellular immunity, controlling cell cycle or promoting cell apoptosis[ 13 , 14 ]. Moreover, the interferon family has been approved by the Food and Drug Administration for the treatment of tumors[ 15 ].…”

Section: To the Editormentioning

confidence: 99%