SNX10 and PTGDS are associated with the progression and prognosis of cervical squamous cell carcinoma

Abstract

Background Cervical cancer (CC) is the primary cause of death in women. This study sought to investigate the potential mechanism and prognostic genes of CC. Methods We downloaded four gene expression profiles from GEO. The RRA method was used to integrate and screen differentially expressed genes (DEGs) between CC and normal samples. Functional analysis was performed by clusterprofiler. We built PPI network by Search Tool for the Retrieval of Interacting Genes Database (STRING) and selected hub modules via Molecular COmplex Detection (MCODE). CMap database was used to find molecules with therapeutic potential for CC. The hub genes were validated in GEO datasets, Gene Expession Profiling Interactive Analysis (GEPIA), immunohistochemistry, Cox regression analysis, TCGA methylation analysis and ONCOMINE were carried out. ROC curve analysis and GSEA were also performed to describe the prognostic significance of hub genes. Results Functional analysis revealed that 147 DEGs were significantly enriched in binding, cell proliferation, transcriptional activity and cell cycle regulation. PPI network screened 30 hub genes, with CDK1 having the strongest connectivity with CC. Cmap showed that apigenin, thioguanine and trichostatin A might be used to treat CC(P < 0.05). Eight genes (APOD, CXCL8, MMP1, MMP3, PLOD2, PTGDS, SNX10 and SPP1) were screened out through GEPIA. Of them, only PTGDS and SNX10 had not appeared in previous studies about CC. The validation in GEO showed that PTGDS showed low expression while SNX10 presented high expression in tumor tissues. Their expression profiles were consistent with the results in immunohistochemistry. ROC curve analysis indicated that the model had a good diagnostic efficiency (AUC = 0.738). GSEA analysis demonstrated that the two genes were correlated with the chemokine signaling pathway (P < 0.05). TCGA methylation analysis showed that patients with lowly-expressed and highly-methylated PTGDS had a worse prognosis than those with highly-expressed and lowly-methylated PTGDS (p = 0.037). Cox regression analysis showed that SNX10 and PTGDS were independent prognostic indicators for OS among CC patients (P = 0.007 and 0.003). Conclusions PTGDS and SNX10 showed abnormal expression and methylation in CC. Both genes might have high prognostic value of CC patients.

A risk prediction model mediated by genes of APOD/APOC1/SQLE associates with prognosis in cervical cancer

“…After regression analysis, 3 genes such as APOD, APOC1 and SQLE were obtained as prognostic genes and prognostic risk models were constructed. According to previous studies, APOD was an immune-related gene and is associated with the risk of multiple types of cancer such as gastric cancer [ 28 ], thyroid cancer [ 29 ], breast cancer and cervical cancer [ 30 ], which was also considered as one of prognostic signatures in cancer. APOC1 was reported as an oncogene to promote tumorigenesis and progression of glioblastoma [ 31 ], gastric cancer [ 32 ], hepatocellular carcinoma [ 33 ], breast cancer [ 34 ] and so on.…”

CircRNA-Based Cervical Cancer Prognosis Model, Immunological Validation and Drug Prediction

“…So far, microarray and high-throughput sequencing techniques have been utilized to identify the potential therapeutic targets of CC. Previous studies usually construct single populations or have small sample sizes, which has restricted their reliability [ 28 ]. This study integrated samples from 3 databases to investigate the roles and ceRNA network and immune infiltration in CC as well as the potential regulatory mechanism, and to explore the key prognostic biomarkers.…”

“…Interestingly, HK2 , SLC22A3 and SNX10 have been reported to be related to CC. Jiang P et al discovered that SNX10 was an independent prognostic factor for OS of CC patients, which was highly expressed in tumor tissues [ 28 ]. Wang Q et al reported that METTL3 enhanced the HK2 stability through the YTHDF1-mediated m6A modification, thus promoting the Warburg effect of CC, which might shed new light on CC treatment [ 34 ].…”

Ropivacaine inhibits the proliferation and metastasis of gastric cancer cells via the SNX10/SRC/STAT3 pathway

“…Sorting nexin 10 (SNX10) is a protein that plays a critical role in intracellular protein trafficking and sorting (Cullen, 2008; Cullen & Korswagen, 2011). SNX10 has been demonstrated to be associated with cervical squamous cell carcinoma (Jiang et al., 2021), colorectal cancer (Le et al., 2018; Zhang, Yang, et al., 2020), and glioblastoma (Gimple et al., 2023). The non‐receptor tyrosine kinase SRC regulates multiple cellular processes, including cell growth, migration, and invasion (Baumgartner et al., 2008; Yang et al., 2014).…”

“…been demonstrated to be associated with cervical squamous cell carcinoma (Jiang et al, 2021), colorectal cancer (Le et al, 2018;, and glioblastoma (Gimple et al, 2023). The non-receptor tyrosine kinase SRC regulates multiple cellular processes, including cell growth, migration, and invasion (Baumgartner et al, 2008;Yang et al, 2014).…”