Identification and Validation of the Anoikis-Related Gene Signature as a Novel Prognostic Model for Cervical Squamous Cell Carcinoma, Endocervical Adenocarcinoma, and Revelation Immune Infiltration

Medicina (Kaunas). 2023 Feb 13;59(2):358. doi: 10.3390/medicina59020358.

Abstract

Background and Objectives: Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are malignant disorders with adverse prognoses for advanced patients. Anoikis, which is involved in tumor metastasis, facilitates the survival and separation of tumor cells from their initial site. Unfortunately, it is rarely studied, and in the literature, studies have only addressed the prognosis character of anoikis for patients with CESC. Materials and Methods: We utilized anoikis-related genes (ANRGs) to construct a prognostic signature in CESC patients that were selected from the Genecards and Harmonizome portals. Furthermore, we revealed the underlying clinical value of this signature for clinical maneuvers by providing clinical specialists with an innovative nomogram on the basis of ANRGs. Finally, we investigated the immune microenvironment and drug sensitivity in different risk groups. Results: We screened six genes from fifty-eight anoikis-related differentially expressed genes in the TCGA-CESC cohort, and we constructed a prognostic signature. Then, we built a nomogram combined with CESC clinicopathological traits and risk scores, which demonstrated that this model may improve the prognosis of CESC patients in clinical therapy. Next, the prognostic risk scores were confirmed to be an independent prognostic indicator. Additionally, we programmed a series of analyses, which included immune infiltration analysis, therapy-related analysis, and GSVA enrichment analysis, to identify the functions and mechanisms of the prognostic models during the progression of cancer in CESC patients. Finally, we performed quantitative reverse transcription polymerase chain reaction (qRT-PCR) to verify the six ANRGs. Conclusions: The present discovery verified that the predictive 6-anoikis-related gene (6-ANRG) signature and nomogram serve as imperative factors that might notably impact a CESC patient's prognosis, and they may be able to provide new clinical evidence to assume the role of underlying biological biomarkers and thus become indispensable indicators for prospective diagnoses and advancing therapy.

Keywords: anoikis; cervical squamous cell carcinoma; endocervical adenocarcinoma; prognosis; therapeutic target.

MeSH terms

  • Adenocarcinoma*
  • Anoikis
  • Carcinoma, Squamous Cell*
  • Female
  • Humans
  • Neoplasms, Connective Tissue*
  • Prognosis
  • Prospective Studies
  • Tumor Microenvironment
  • Uterine Cervical Neoplasms*