Pan-cancer analysis of homeodomain-containing gene C10 and its carcinogenesis in lung adenocarcinoma

Aging (Albany NY). 2023 Dec 27;15(24):15243-15266. doi: 10.18632/aging.205348. Epub 2023 Dec 27.

Abstract

We found elevated homeodomain-containing gene C10 (HOXC10) showed dual roles in cancers' prognosis. Some signal pathways associated with tumor were totally positively enriched in HOXC10 for whole cancers. On the contrary, Notch signaling, Wnt-beta catenin signaling, myogenesis, and Hedgehog signaling were almost negatively enriched in HOXC10. Some pathways showed dual roles such as Kras signaling, interferon gram and alpha response, IL6/JAK/STAT3, IL2/STAT5 signaling. HOXC10 was associated with tumor mutation burden and microsatellite instability. HOXC10 also was associated with tumor microenvironment and immune status. HOXC10 was negatively associated with immune score in most cancers except colon adenocarcinoma. The correlations of HOXC10 with immune-related genes presented dual roles in different cancers. Results from our clinical samples indicated that HOXC10 was an independent predictor for distant metastasis-free survival in lung adenocarcinoma (LUAD). Notably, the high levels of HOXC10 were positively correlated with the expression of angiogenic markers, vascular endothelial growth factor and microvessel density, and the number of CTC clusters. Our results demonstrated that aberrant expression happened in most cancers, which also affected the clinical prognosis and involved in progression via multiple signal pathways cancers. HOXC10 overexpression plays an important role in the aggression and metastasis in LUAD, which indicated a potential therapeutic target and an independent factor for the prognosis for LUAD patients.

Keywords: CTC clusters; HOXC10; LUAD; MVD; VEGFA.

MeSH terms

  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma* / genetics
  • Carcinogenesis / genetics
  • Hedgehog Proteins
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Lung Neoplasms* / genetics
  • Prognosis
  • Tumor Microenvironment / genetics
  • Vascular Endothelial Growth Factor A

Substances

  • Hedgehog Proteins
  • Homeodomain Proteins
  • HOXC10 protein, human
  • Vascular Endothelial Growth Factor A