Role of APLP2 in the prognosis and clinicopathology of renal cell carcinoma

Gao, Lijian; Zhao, Hongda; Zhang, Dongqing; Zhou, Chuanen; Wang, Hui; Ren, Chantao; Liu, Yaxiao; Xia, Yangyang; Shi, Benkang

doi:10.3892/ol.2018.9577

Cited by 5 publications

(6 citation statements)

References 20 publications

(20 reference statements)

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“…Hub genes have been identified, for example, APLP2, IFIT1, IFIT3, and CDC34. APLP2 expression was significantly related to disease-specific survival in renal cell carcinoma (33). It could be hypothesized that MMP25 was able to interact with multiple key genes to affect the progression of head and neck cancer.…”

Section: Discussionmentioning

confidence: 99%

MMP25 Regulates Immune Infiltration Level and Survival Outcome in Head and Neck Cancer Patients

Liang

Guan

et al. 2020

Front. Oncol.

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Background: MMP25 is a critical gene of matrix metalloproteinases (MMPs). However, the molecular mechanism of MMP25 in head and neck cancer pathogenesis remains unclear. Methods: MMP25 expression was analyzed using The Cancer Genome Atlas (TCGA) database, and its influence on clinical prognosis was performed using Kaplan-Meier and Cox regression analyses. The correlation between MMP25 and immune infiltration was investigated by CIBERSORT, TIMER, and ESTIMATE. In addition, the relationship between MMP25 expression and molecular mechanisms was analyzed by gene set enrichment analysis (GSEA), gene ontology (GO), and weighted gene co-expression network analysis (WGCNA). Results: MMP25 expression level correlated with prognosis and immune infiltrating levels, especially activated CD4 + memory T cells, in head and neck cancer. Moreover, MMP25 expression potentially mediated genes, such as IRF8, IKZF1, and DOCK2, and tumor-associated pathways, including p53 signaling, PI3K/AKT/mTOR signaling, and JAK/STAT signaling pathway. Conclusions: These findings suggested that MMP25 plays a critical role in the prognosis and immune infiltration level of head and neck cancer. In addition, MMP25 expression significantly correlated with the regulation of various oncogenes and tumor-related pathways.

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Section: Discussionmentioning

confidence: 99%

MMP25 Regulates Immune Infiltration Level and Survival Outcome in Head and Neck Cancer Patients

Liang

Guan

et al. 2020

Front. Oncol.

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“…Gao et al. investigated renal cell carcinoma and found that APLP2 expression serves as an independent predictor of survival prognosis (P=0.026), indicating its significance in patient survival and prognosis ( 38 ). Additionally, Poelaert et al.…”

Section: Discussionmentioning

confidence: 99%

“…This model demonstrated high predictive performance in multiple cohorts, revealing that APLP2 influences the oncogenic processes of hepatocellular liver cancer by regulating apoptosis and the cell cycle (37). Gao et al investigated renal cell carcinoma and found that APLP2 expression serves as an independent predictor of survival prognosis (P=0.026), indicating its significance in patient survival and prognosis (38). Additionally, Poelaert et al identified increased APLP2 expression in pancreatic cancer epithelium compared to pancreatic intraepithelial neoplasia epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptomics reveals heterogeneity in esophageal squamous epithelial cells and constructs models for predicting patient prognosis and immunotherapy

Li,

Song,

Zhang

et al. 2023

Front. Immunol.

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BackgroundEsophageal squamous cell carcinoma (ESCC), characterized by its high invasiveness and malignant potential, has long been a formidable challenge in terms of treatment.MethodsA variety of advanced analytical techniques are employed, including single-cell RNA sequencing (scRNA-seq), cell trajectory inference, transcription factor regulatory network analysis, GSVA enrichment analysis, mutation profile construction, and the inference of potential immunotherapeutic drugs. The purpose is to conduct a more comprehensive exploration of the heterogeneity among malignant squamous epithelial cell subgroups within the ESCC microenvironment and establish a model for predicting the prognosis and immunotherapy outcomes of ESCC patients.ResultsAn analysis was conducted through scRNA-seq, and three Cluster of malignant epithelial cells were identified using the infer CNV method. Cluster 0 was found to exhibit high invasiveness, whereas Cluster 1 displayed prominent characteristics associated with epithelial-mesenchymal transition. Confirmation of these findings was provided through cell trajectory analysis, which positioned Cluster 0 at the initiation stage of development and Cluster 1 at the final developmental stage. The abundance of Cluster 0-2 groups in TCGA-LUAD samples was assessed using ssGSEA and subsequently categorized into high and low-expression groups. Notably, it was observed that Cluster 0-1 had a significant impact on survival (p<0.05). Furthermore, GSVA enrichment analysis demonstrated heightened activity in hallmark pathways for Cluster 0, whereas Cluster 1 exhibited notable enrichment in pathways related to cell proliferation. It is noteworthy that a prognostic model was established utilizing feature genes from Cluster 0-1, employing the Lasso and stepwise regression methods. The results revealed that in TCGA and GSE53624 cohorts, the low-risk group demonstrated significantly higher overall survival and increased levels of immune infiltration. An examination of four external immunotherapy cohorts unveiled that the low-risk group exhibited improved immunotherapeutic efficacy. Additionally, more meaningful treatment options were identified for the low-risk group.ConclusionThe findings revealed distinct interactions between malignant epithelial cells of ESCC and subgroups within the tumor microenvironment. Two cell clusters, strongly linked to survival, were pinpointed, and a signature was formulated. This signature is expected to play a crucial role in identifying and advancing precision medicine approaches for the treatment of ESCC.

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“…In this study, we investigated the functions and mechanisms of action of APLP2 in the pathogenesis of CSCC. Although aberrant APLP2 expression is frequently observed in various types of cancer, its functions in cancer progression remain largely unknown (4,15,(32)(33)(34)(35). Currently, controversy exists as to whether APLP2 is an oncogene or a tumor-suppressor gene involved in tumor progression.…”

Section: Discussionmentioning

confidence: 99%

“…APLP2 has tumor-suppressive functions in renal cell carcinoma (33). In renal cell carcinoma, APLP2 expression was significantly reduced in tumor tissues compared to corresponding normal tissues, and a low expression of APLP2 was found to be a poor prognostic indicator in patients (33).…”

Section: Amyloid Precursor-like Protein 2 (Aplp2) and Major Histocomp...mentioning

confidence: 96%

Implication of Amyloid Precursor-like Protein 2 Expression in Cutaneous Squamous Cell Carcinoma Pathogenesis

HUANG,

YANG,

et al. 2023

In Vivo

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Background/Aim: Regulatory functions of amyloid precursor-like protein 2 (APLP2) expression in intracellular trafficking of major histocompatibility complex class I (MHC-I) and biological behavior of tumor cells have been reported in various types of malignancies but not in cutaneous squamous cell carcinoma (CSCC). This study aimed to investigate the role of APLP2 expression in the pathogenesis of CSCC. Patients and Methods: The expression of APLP2 and a key modulator of cancer immune escape, MHC-I, were determined in CSCC tissue samples obtained from 141 patients using immunohistochemistry. The regulatory effects of APLP2 expression on the biological behavior and surface expression of MHC-I in CSCC cells were investigated by trypan blue assay, Matrigel invasion assay, and in vivo xenograft analysis. Results: APLP2 immunoreactivity was high in 73 (51.8%) tissue samples from patients with CSCC and was significantly related to subcutaneous fat invasion and poor prognosis in our cohort. Moreover, proliferation of and invasion by CSCC cells were significantly reduced after APLP2 knockdown in CSCC cells both in vitro and in vivo. A significant association was found between APLP2 and membrane MHC-I expression in patients with CSCC. In vivo xenograft analysis showed that APLP2 knockdown increased membrane MHC-I expression in CSCC cells. Conclusion: APLP2 not only acts as an oncogene in CSCC progression but also as a possible modulator of cancer immune escape by influencing MHC-Iexpression on the cell surface. APLP2 may serve as a novel molecular biomarker and therapeutic target for patients with CSCC.

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Role of APLP2 in the prognosis and clinicopathology of renal cell carcinoma

Cited by 5 publications

References 20 publications

MMP25 Regulates Immune Infiltration Level and Survival Outcome in Head and Neck Cancer Patients

MMP25 Regulates Immune Infiltration Level and Survival Outcome in Head and Neck Cancer Patients

Single-cell transcriptomics reveals heterogeneity in esophageal squamous epithelial cells and constructs models for predicting patient prognosis and immunotherapy

Implication of Amyloid Precursor-like Protein 2 Expression in Cutaneous Squamous Cell Carcinoma Pathogenesis

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