Bioinformatics analysis identified MMP14 and COL12A1 as immune-related biomarkers associated with pancreatic adenocarcinoma prognosis

Li, Yuexian; Zhou, Shanshan; Wei, Biwei; Qin, Mengbin; Liang, Zhihai

doi:10.3934/mbe.2021296

Cited by 15 publications

(12 citation statements)

References 60 publications

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“…Moreover, Feng et al also reported that patients with higher expression of DCBLD2 have lower disease-free survival (DFS) rates (55). Similarly, MMP14 was also revealed to be a poor prognostic marker for PDAC patients (56). In parallel with our findings in the pathway enrichment analysis, in a pancreatic cancer related complementary EMT model, it was shown that CHST11, a modifier of glycosaminoglycan sulfation was significantly upregulated in the EMT model (57).…”

Section: Discussionsupporting

confidence: 82%

A cancer-associated fibroblast gene signature predicts prognosis and therapy response in patients with pancreatic cancer

et al. 2022

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Pancreatic cancer is a lethal malignancy with a 5-year survival rate of about 10% in the United States, and it is becoming an increasingly prominent cause of cancer death. Among pancreatic cancer patients, pancreatic ductal adenocarcinoma (PDAC) accounts for more than 90% of all cases and has a very poor prognosis with an average survival of only 1 year in about 18% of all tumor stages. In the past years, there has been an increasing interest in cancer-associated fibroblasts (CAFs) and their roles in PDAC. Recent data reveals that CAFs in PDAC are heterogeneous and various CAF subtypes have been demonstrated to promote tumor development while others hinder cancer proliferation. Furthermore, CAFs and other stromal populations can be potentially used as novel prognostic markers in cancer. In the present study, in order to evaluate the prognostic value of CAFs in PDAC, CAF infiltration rate was evaluated in 4 PDAC datasets of TCGA, GEO, and ArrayExpress databases and differentially expressed genes (DEGs) between CAF-high and CAF-low patients were identified. Subsequently, a CAF-based gene expression signature was developed and studied for its association with overall survival (OS). Additionally, functional enrichment analysis, somatic alteration analysis, and prognostic risk model construction was conducted on the identified DEGs. Finally, oncoPredict algorithm was implemented to assess drug sensitivity prediction between high- and low-risk cohorts. Our results revealed that CAF risk-high patients have a worse survival rate and increased CAF infiltration is a poor prognostic indicator in pancreatic cancer. Functional enrichment analysis also revealed that “extracellular matrix organization” and “vasculature development” were the top enriched pathways among the identified DEGs. We also developed a panel of 12 genes, which in additional to its prognostic value, could predict higher chemotherapy resistance rate. This CAF-based panel can be potentially utilized alone or in conjunction with other clinical parameters to make early predictions and prognosticate responsiveness to treatment in PDAC patients. Indeed, it is necessary to conduct extensive prospective investigations to confirm the clinical utility of these findings.

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Section: Discussionsupporting

confidence: 82%

A cancer-associated fibroblast gene signature predicts prognosis and therapy response in patients with pancreatic cancer

et al. 2022

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“…It suggested that COL12A1 may participate in the formation of tumor immunosuppressive microenvironment in HER2-positive BC. Consistent with our research report, it was previously reported that COL12A1 strongly impacted immune cell infiltrations [18].…”

Section: Discussionsupporting

confidence: 93%

COL12A1 as a prognostic biomarker in HER2-enriched breast cancer and its association with immune infiltration

2022

European Journal of Gynaecological Oncology

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To inspect the expression, characteristics, clinical prognostic value and the level of immune infiltration of Collagen Type XII Alpha 1 Chain (COL12A1) in breast cancer (BC) using bioinformatics. We investigated the expression of COL12A1 in breast cancer and normal breast tissues using Tumor IMmune Estimation Resource (TIMER2.0) and the University of ALabama at Birmingham CANcer data analysis Portal (UALCAN). The correlation between COL12A1 and overall survival (OS) was determined using Kaplan-Meier Plotter in BC. The correlation between COL12A1, immune infiltrating cells and immune checkpoints was detected via TIMER2.0. We found that the expression of COL12A1 was significantly higher in BC tissues than in normal tissues. A higher expression level of COL12A1 correlated with lymph node metastasis and worse OS in human epidermal growth factor receptor 2 (HER2)-enriched BC patients. Moreover, COL12A1 was positively correlated with M2 macrophages and immune checkpoint programmed cell death 1 ligand 2 (PDCD1LG2) but negatively correlated with activated natural killer (NK) cells and cluster of differentiation 8 (CD8)+ T cells in HER2-positive BC. COL12A1 might act as a biomarker indicating poor prognosis in HER2-enriched BC and correlate with immune infiltration in HER2-positive BC.

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“…Wan et al identified FOXD3-AS1 as a cancer-promoting gene in glioma [ 54 ]. In addition, Li et al suggested that downregulation of COL12A1 has a key role in regulating tumor immune interactions [ 43 ]. Therefore, further studies are needed to confirm the biological role of these RBPMS downstream genes and their diagnostic, prognostic and/or therapeutic potential in ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of the RBPMS Splice Variants Inhibits Cell Proliferation in Ovarian Cancer Cells

Rabelo-Fernández

Noriega-Rivera

Santana‐Rivera

et al. 2022

IJMS

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RNA-Binding Protein with Multiple Splicing (RBPMS) is a member of family proteins that bind to nascent RNA transcripts and regulate their splicing, localization, and stability. Evidence indicates that RBPMS controls the activity of transcription factors associated with cell growth and proliferation, including AP-1 and Smads. Three major RBPMS protein splice variants (RBPMSA, RBPMSB, and RBPMSC) have been described in the literature. We previously reported that reduced RBPMS levels decreased the sensitivity of ovarian cancer cells to cisplatin treatment. However, little is known about the biological role of the RBPMS splice variants in ovarian cancer cells. We performed RT-PCR and Western blots and observed that both RBPMSA and RBPMSC are reduced at the mRNA and protein levels in cisplatin resistant as compared with cisplatin sensitive ovarian cancer cells. The mRNA and protein levels of RBPMSB were not detectable in any of the ovarian cancer cells tested. To better understand the biological role of each RBPMSA and RBPMSC, we transfected these two splice variants in the A2780CP20 and OVCAR3CIS cisplatin resistant ovarian cancer cells and performed cell proliferation, cell migration, and invasion assays. Compared with control clones, a significant reduction in the number of colonies, colony size, cell migration, and invasion was observed with RBPMSA and RBPMSC overexpressed cells. Moreover, A2780CP20-RBPMSA and A2780CP20-RBPMSC clones showed reduced senescence-associated β-galactosidase (β-Gal)-levels when compared with control clones. A2780CP20-RBPMSA clones were more sensitive to cisplatin treatment as compared with A2780CP20-RBPMSC clones. The A2780CP20-RBPMSA and A2780CP20-RBPMSC clones subcutaneously injected into athymic nude mice formed smaller tumors as compared with A2780CP20-EV control group. Additionally, immunohistochemical analysis showed lower proliferation (Ki67) and angiogenesis (CD31) staining in tissue sections of A2780CP20-RBPMSA and A2780CP20-RBPMSC tumors compared with controls. RNAseq studies revealed many common RNA transcripts altered in A2780CP20-RBPMSA and A2780CP20-RBPMSC clones. Unique RNA transcripts deregulated by each RBPMS variant were also observed. Kaplan–Meier (KM) plotter database information identified clinically relevant RBPMSA and RBPMSC downstream effectors. These studies suggest that increased levels of RBPMSA and RBPMSC reduce cell proliferation in ovarian cancer cells. However, only RBPMSA expression levels were associated with the sensitivity of ovarian cancer cells to cisplatin treatment.

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Bioinformatics analysis identified MMP14 and COL12A1 as immune-related biomarkers associated with pancreatic adenocarcinoma prognosis

Cited by 15 publications

References 60 publications

A cancer-associated fibroblast gene signature predicts prognosis and therapy response in patients with pancreatic cancer

A cancer-associated fibroblast gene signature predicts prognosis and therapy response in patients with pancreatic cancer

COL12A1 as a prognostic biomarker in HER2-enriched breast cancer and its association with immune infiltration

Increased Expression of the RBPMS Splice Variants Inhibits Cell Proliferation in Ovarian Cancer Cells

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