Identification of Survival-Associated Hub Genes in Pancreatic Adenocarcinoma Based on WGCNA

Abstract

Pancreatic adenocarcinoma is one of the leading causes of cancer-related death worldwide. Since little clinical symptoms were shown in the early period of pancreatic adenocarcinoma, most patients were found to carry metastases when diagnosis. The lack of effective diagnosis biomarkers and therapeutic targets makes pancreatic adenocarcinoma difficult to screen and cure. The fundamental problem is we know very little about the regulatory mechanisms during carcinogenesis. Here, we employed weighted gene co-expression network analysis (WGCNA) to build gene interaction network using expression profile of pancreatic adenocarcinoma from The Cancer Genome Atlas (TCGA). STRING was used for the construction and visualization of biological networks. A total of 22 modules were detected in the network, among which yellow and pink modules showed the most significant associations with pancreatic adenocarcinoma. Dozens of new genes including PKMYT1, WDHD1, ASF1B, and RAD18 were identified. Further survival analysis yielded their valuable effects on the diagnosis and treatment of pancreatic adenocarcinoma. Our study pioneered network-based algorithm in the application of tumor etiology and discovered several promising regulators for pancreatic adenocarcinoma detection and therapy.

miR-24-3p Regulates Epithelial–Mesenchymal Transition and the Malignant Phenotype of Pancreatic Adenocarcinoma by Regulating ASF1B Expression

“…In this study, we demonstrated that ASF1B is highly expressed in pancreatic cancer and its high expression promotes the migration, invasion and EMT in PDAC cells. Consistently, Huang et al ( 2022 ) applied WGCNA analysis using pancreatic cancer datasets in TCGA and found that the upregulation of ASF1B is correlated with the occurrence of pancreatic cancer. In addition, high expression of ASF1B level was also found to be associated with poor prognosis in different cancers (Hu et al 2021 ; Feng et al 2021 ).…”

Knockdown of CENPM activates cGAS-STING pathway to inhibit ovarian cancer by promoting pyroptosis

“…Based on the analysis of 91 OC samples and 22 normal ovarian tissues from GSE18520, GSE54388, and GSE27651 gene expression profiles, KIF15 has promising predictive value for the development and prognosis of OC and can be used as a candidate target for the diagnosis and treatment of OC [ 45 ]. To construct gene interaction networks based on weighted gene co-expression network analysis, using pancreatic cancer expression profiles from the Cancer Genome Atlas, ASF1B is a promising regulator for pancreatic cancer detection and treatment [ 46 ]. All in all, KIFC1, PCLAF, CDCA5, KNTC1, MCM3, OIP5, CENPM, KIF15, and ASF1B are hub genes of OC, which had good specificity and sensitivity in the diagnosis of OC.…”

WD Repeat and HMG Box DNA Binding Protein 1: An Oncoprotein at the Hub of Tumorigenesis and a Novel Therapeutic Target

“…Enhancing the ubiquitination degradation of MAPRE2 Cisplatin resistance [24] As a cell cycle regulator and a downstream molecule in the PI3K/AKT pathway The occurrence and survival of tumors [19] Regulating the ATM signaling pathway Radiosensitivity of cancer [25] Triple-negative breast cancer As a downstream target of PTEN-AKT signaling Tumor cells survival [22] Hepatocellular carcinoma Co-expressed genes analysis As a biomarker for diagnosis and prognosis [82] Cholangiocarcinoma Inhibited by miR-494 Tumor formation and metastasis [20] Pancreatic adenocarcinoma Weighted gene co-expression network analysis As a hub gene for tumor progression [83] Cervical cancer Weighted gene co-expression network analysis As a hub gene for cancer lymph node metastasis [21] Ovarian cancer Regulated by ATM-and Rad3-related pathway Cisplatin resistance [23] Activating the FA pathway Cisplatin resistance [84] Acute myeloid leukemia A large-scale loss of-function RNA interference Tumor growth and viability [85] Integrin alpha V, ITGAV; S-phase kinase-associated protein 2, Skp2; Microtubule-associated protein RP/EB family member 2, MAPRE2; Ataxia-telangiectasia mutated, ATM; Fanconi anemia, FA.…”