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Background <p>Integrin alpha 6 (ITGA6) has been implicated in tumorigenesis and progression, but its roles across cancer types and its functional significance in uveal melanoma (UVM) remain incompletely characterized.</p> Methods <p>We performed an integrated pan-cancer analysis of ITGA6 expression, diagnostic performance, prognostic relevance, immune associations, pathway activity, and drug sensitivity. In addition, we evaluated its functional role in UVM using in vitro assays, including proliferation, migration, invasion, and colony formation experiments following ITGA6 knockdown.</p> Results <p>ITGA6 was upregulated in multiple tumor types, including lung squamous cell carcinoma and hepatocellular carcinoma. Diagnostic analysis indicated strong discriminatory value in several cancers, with AUC values &gt; 0.95 in pheochromocytoma/paraganglioma and cholangiocarcinoma, and AUC values of 0.85–0.95 in pancreatic adenocarcinoma, hepatocellular carcinoma, kidney chromophobe, and head and neck squamous cell carcinoma. Survival analyses revealed that the prognostic association of ITGA6 was cancer-type dependent: higher ITGA6 expression correlated with better outcomes in skin cutaneous melanoma and uterine corpus endometrial carcinoma, but with worse outcomes in lung adenocarcinoma, lower-grade glioma, and UVM. In UVM, elevated ITGA6 expression was associated with poorer overall survival, progression-free interval, and disease-specific survival, and was positively correlated with immune infiltration and malignant functional states. ITGA6 expression showed positive correlations with all 14 functional state gene sets in UVM, with particularly strong correlations for angiogenesis, proliferation, and stemness. Pathway analyses further suggested that high ITGA6 expression was associated with epithelial-mesenchymal transition and TNF-α/NF-κB signaling. Drug sensitivity analyses identified several compounds that may be associated with ITGA6-related transcriptional signatures. Functional experiments showed that ITGA6 knockdown significantly inhibited proliferation, migration, invasion, and colony formation in UVM cells.</p> Conclusions <p>These findings suggest that ITGA6 may serve as a potential diagnostic and prognostic biomarker in selected cancers and support a tumor-promoting role for ITGA6 in UVM.</p>

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Pan-cancer atlas of ITGA6 unveils its multifaceted oncogenic roles and therapeutic potential in uveal melanoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月1日

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  • Chao Shi,
  • Menghui Duan,
  • Juan Li,
  • Fangxia Zhang,
  • Yiming Guo,
  • Tu Lu,
  • Wei Zhao,
  • Yang Liu

摘要

Background

Integrin alpha 6 (ITGA6) has been implicated in tumorigenesis and progression, but its roles across cancer types and its functional significance in uveal melanoma (UVM) remain incompletely characterized.

Methods

We performed an integrated pan-cancer analysis of ITGA6 expression, diagnostic performance, prognostic relevance, immune associations, pathway activity, and drug sensitivity. In addition, we evaluated its functional role in UVM using in vitro assays, including proliferation, migration, invasion, and colony formation experiments following ITGA6 knockdown.

Results

ITGA6 was upregulated in multiple tumor types, including lung squamous cell carcinoma and hepatocellular carcinoma. Diagnostic analysis indicated strong discriminatory value in several cancers, with AUC values > 0.95 in pheochromocytoma/paraganglioma and cholangiocarcinoma, and AUC values of 0.85–0.95 in pancreatic adenocarcinoma, hepatocellular carcinoma, kidney chromophobe, and head and neck squamous cell carcinoma. Survival analyses revealed that the prognostic association of ITGA6 was cancer-type dependent: higher ITGA6 expression correlated with better outcomes in skin cutaneous melanoma and uterine corpus endometrial carcinoma, but with worse outcomes in lung adenocarcinoma, lower-grade glioma, and UVM. In UVM, elevated ITGA6 expression was associated with poorer overall survival, progression-free interval, and disease-specific survival, and was positively correlated with immune infiltration and malignant functional states. ITGA6 expression showed positive correlations with all 14 functional state gene sets in UVM, with particularly strong correlations for angiogenesis, proliferation, and stemness. Pathway analyses further suggested that high ITGA6 expression was associated with epithelial-mesenchymal transition and TNF-α/NF-κB signaling. Drug sensitivity analyses identified several compounds that may be associated with ITGA6-related transcriptional signatures. Functional experiments showed that ITGA6 knockdown significantly inhibited proliferation, migration, invasion, and colony formation in UVM cells.

Conclusions

These findings suggest that ITGA6 may serve as a potential diagnostic and prognostic biomarker in selected cancers and support a tumor-promoting role for ITGA6 in UVM.