Clinical and prognostic value of the C-Met/HGF signaling pathway in cervical cancer

Abstract Background: This study aimed to explore the expression of Family with sequence similarity 83 (FAM83) members in cervical cancer, its prognostic value, related signaling pathways, regulatory mechanisms, and immune infiltration. It’s of great value to explore the potential role of FAM83 family in cervical cancer and provide a new scientific basis for targeted therapy.Methods: The expression, gene mutations and prognostic value of FAM83 family members in cervical cancer were analyzed by various bioinformatics tools and databases. We further explored the interaction regulation network and immune infiltration between FAM83 family members and their closely related genes through a series of databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathways (KEGG) enrichment were also conducted.Results: This study showed that the expression levels of FAM83A/B/C/D/E/F/G/H gene were upregulated in cervical cancer, the expression of FAM83B/C/D/E/F/G/H were related to tumor stages of cervical cancer, and the promoter methylation of FAM83A/D/E/F/G genes in cervical cancer were lower than those in normal tissues. What’s more, high expression of FAM83A, FAM83B, and FAM83H mRNA was associated with shortened overall survival. GO results showed that FAM83A, FAM83B, and FAM83H and their closely related genes can play an important role in cell-cell junction, calcium-dependent protein binding, regulation of peptidase activity, inflammatory response. KEGG analysis results showed that FAM83A, FAM83B, and FAM83H and their closely related genes were significantly enriched in cancer pathways, estrogen signaling pathway, MAPK signaling pathway. Furthermore, FAM83A, FAM83B, and FAM83H are all closely related to lymphocytes (Tcm_CD4, Tcm_CD8, and neutrophils) and immunomodulators (TGFBR1, TGFB1, and TNFSF9).Conclusions: With multiple databases, we found that the high expression of FAM83A, FAM83B, and FAM83H were associated with the shortened survival time and poor prognosis in patients with cervical cancer, and also closely correlated with lymphocytes and immune infiltration, suggesting that FAM83A, FAM83B, and FAM83H played an important role in the occurrence, development, malignant biological behavior, and immune infilatration of cervical cancer, which provides an important theoretical basis for early diagnosis and targeted therapy for cervical cancer.

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THE PROGNOSTIC VALUE OF PRETHERAPEUTIC HYPONATREMIA IN PATIENTS WITH CERVICAL CANCER.

10.26226/morressier.597eedbfd462b80296ca0d86 ◽

2017 ◽

Author(s):

Lisa Gensthaler

Keyword(s):

Cervical Cancer ◽

Prognostic Value

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DCBLD1 is associated with the integrin signaling pathway and has prognostic value in non-small cell lung and invasive breast carcinoma

Scientific Reports ◽

10.1038/s41598-021-92090-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Guillaume B. Cardin ◽

Monique Bernard ◽

Francis Rodier ◽

Apostolos Christopoulos

Keyword(s):

Breast Carcinoma ◽

Signaling Pathway ◽

Prognostic Value ◽

Colorectal Adenocarcinoma ◽

Prostate Adenocarcinoma ◽

Small Cell ◽

Invasive Breast Carcinoma ◽

Integrin Signaling ◽

Small Cell Lung ◽

And Function

AbstractGermline single nucleotide polymorphisms in the promoter region of the DCBLD1 gene are associated with non-smoking cases of both non-small cell lung carcinoma (NSCLC) and human papillomavirus-negative head and neck cancer. However the clinical relevance and function of DCBLD1 remain unclear. This multicenter retrospective study was designed to evaluate the prognostic value and function of DCBLD1 in the four main solid cancers: NSCLC, invasive breast carcinoma, colorectal adenocarcinoma and prostate adenocarcinoma. We included the following cohorts: GSE81089 NSCLC, METABRIC invasive breast carcinoma, GSE14333 colorectal adenocarcinoma, GSE70770 prostate adenocarcinoma and The Cancer Genome Atlas (TCGA) Firehose Legacy cohorts of all four cancers. DCBLD1 gene expression was associated with a worse overall survival in multivariate analyses for both NSCLC cohorts (TCGA: P = 0.03 and GSE81089: P = 0.04) and both invasive breast carcinoma cohorts (TCGA: P = 0.02 and METABRIC: P < 0.001). Patients with high DCBLD1 expression showed an upregulation of the integrin signaling pathway in comparison to those with low DCBLD1 expression in the TCGA NSCLC cohort (FDR = 5.16 × 10–14) and TCGA invasive breast carcinoma cohort (FDR = 1.94 × 10–05).

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Immune negative regulator TIPE2 inhibits cervical squamous cancer progression through Erk1/2 signaling

Open Life Sciences ◽

10.1515/biol-2019-0059 ◽

2019 ◽

Vol 14 (1) ◽

pp. 528-536

Author(s):

Li-Qiong Huang ◽

Bo Zheng ◽

Yi He

Keyword(s):

Cervical Cancer ◽

Western Blot ◽

Cancer Cells ◽

Signaling Pathway ◽

Erk Signaling ◽

Over Expression ◽

Squamous Cancer ◽

Cancer Tissues ◽

Proliferation And Invasion ◽

Cervical Squamous Cancer

AbstractTumor necrosis factor (TNF)-α-induced protein-8-like 2, or TIPE2, is a newly found immune negative regulatory molecule. This study further investigated the role of TIPE2 on proliferation and invasion of cervical squamous cancer cells. Expression of TIPE2 was compared in cervical squamous cancer tissues and adjacent normal tissues by Western blot and immunohistochemistry (IHC). Cervical squamous cancer cell lines, SiHa and C33A, were transfected with recombinant plasmid encoding TIPE2 and tested for cytologic characteristics. The impact of TIPE2 on phosphorylation of extracellular signal-regulated kinase (Erk) signaling pathway was also tested by Western blot analysis of key factors. TIPE2 expression was higher in cervical cancer tissues than that in normal tissue. IHC score of tumor tissue was negatively associated with lymphatic metastasis. Over expression of TIPE2 effectively inhibited the proliferation of cervical cancer cells. Wound healing and transwell assay showed that over expression of TIPE2 suppressed cell migration and invasion in vitro. Meanwhile, phosphorylation of Erk1/2 and upstream mitogen-activated protein kinase kinase (MEK) 1/2 was reduced by TIPE2. TIPE2 is negatively related with development of cervical squamous cancer. TIPE2 is an inhibitory factor of proliferation and invasion of cervical squamous cancer cells, probably through inhibiting Erk signaling pathway.

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Comprehensive Analysis of SFRP Family Members Prognostic Value and Immune Infiltration in Gastric Cancer

Life ◽

10.3390/life11060522 ◽

2021 ◽

Vol 11 (6) ◽

pp. 522

Author(s):

Dehua Liu ◽

Chenyu Sun ◽

Nahyun Kim ◽

Chandur Bhan ◽

John Pocholo Whitaker Tuason ◽

...

Keyword(s):

Gastric Cancer ◽

Wnt Signaling ◽

Signaling Pathway ◽

Prognostic Value ◽

Immune Cell ◽

System Development ◽

Wnt Signaling Pathway ◽

Immune System Development ◽

Precision Therapy ◽

Gastric Cancer Patients

Gastric cancer (GC) is the fifth most common cancer globally. Secreted frizzled-related proteins (SFRP) are important elements associated with the Wnt signaling pathway, and its dysregulated expression is found in multiple cancers. However, the function of distinct SFRPs in GC remains poorly understood. We investigated the differential expression, prognostic value, and immune cell infiltration of SFRPs in gastric cancer patients from the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan–Meier plotter, cBioPortal, STRING, Gene-MANIA, DAVID, MethSurv, and TIMER databases. We found that the expression levels of SFRP2 and SFRP4 were significantly increased in GC tissues, whereas the SFRP1 and SFRP5 expressions were reduced. SFRP1, SFRP2, and SFRP5 were significantly correlated with the clinical cancer stage in GC patients. Higher expression of SFRPs was associated with short overall survival (OS) in GC patients. Besides, high SFRPs methylation showed favorable OS in GC patients. The functions of SFRPs were primarily related to the Wnt signaling pathway, immune system development, and basal cell carcinoma. The expression of SFRPs was strongly correlated with immune infiltrating cells, including CD4+ T cells and macrophages in GC. Our study indicated that SFRPs could be potential targets of precision therapy and prognostic biomarkers for the survival of GC patients.

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HOXB4 inhibits the proliferation and tumorigenesis of cervical cancer cells by downregulating the activity of Wnt/β-catenin signaling pathway

Cell Death and Disease ◽

10.1038/s41419-021-03411-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Dan Lei ◽

Wen-Ting Yang ◽

Peng-Sheng Zheng

Keyword(s):

Cervical Cancer ◽

Cell Growth ◽

Signaling Pathway ◽

Cancer Cell ◽

Tumor Formation ◽

Cervical Cancer Cell ◽

Cancer Cell Growth ◽

Bioinformatics Analyses

AbstractHomeobox B4 (HOXB4), which belongs to the homeobox (HOX) family, possesses transcription factor activity and has a crucial role in stem cell self-renewal and tumorigenesis. However, its biological function and exact mechanism in cervical cancer remain unknown. Here, we found that HOXB4 was markedly downregulated in cervical cancer. We demonstrated that HOXB4 obviously suppressed cervical cancer cell proliferation and tumorigenic potential in nude mice. Additionally, HOXB4-induced cell cycle arrest at the transition from the G0/G1 phase to the S phase. Conversely, loss of HOXB4 promoted cervical cancer cell growth both in vitro and in vivo. Bioinformatics analyses and mechanistic studies revealed that HOXB4 inhibited the activity of the Wnt/β-catenin signaling pathway by direct transcriptional repression of β-catenin. Furthermore, β-catenin re-expression rescued HOXB4-induced cervical cancer cell defects. Taken together, these findings suggested that HOXB4 directly transcriptional repressed β-catenin and subsequently inactivated the Wnt/β-catenin signaling pathway, leading to significant inhibition of cervical cancer cell growth and tumor formation.

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