ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2024; 15(3):841-857. doi:10.7150/jca.91627 This issue Cite
Research Paper
Anoikis-related signature identifies tumor microenvironment landscape and predicts prognosis and drug sensitivity in colorectal cancer
1. Taizhou Hospital of Zhejiang Province, Zhejiang University, Linhai, China
2. Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
3. Hospital of Huangyan affiliated to Wenzhou Medical University, Huangyan, Zhejiang, China
4. Department of Gastroenterology, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Linhai, Zhejiang Province, China
5. Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Linhai, Zhejiang Province, China
6. Institute of Digestive Disease, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
#These authors contributed equally to this work
Abstract
Background: Anoikis, a mechanism of programmed apoptosis, plays an important role in growth and metastasis of tumors. However, there are still few available comprehensive reports on the impact of anoikis on colorectal cancer.
Method: A clustering analysis was done on 133 anoikis-related genes in GSE39582, and we compared clinical features between clusters, the tumor microenvironment was analyzed with algorithms such as “Cibersort” and “ssGSEA”. We investigated risk scores of clinical feature groups and anoikis-associated gene mutations after creating a predictive model. We incorporated clinical traits to build a nomogram. Additionally, the quantitative real-time PCR was employed to investigate the mRNA expression of selected anoikis-associated genes.
Result: We identified two anoikis-related clusters with distinct prognoses, clinical characteristics, and biological functions. One of the clusters was associated with anoikis resistance, which activated multiple pathways encouraging tumor metastasis. In our prognostic model, oxaliplatin may be a sensitive drug for low-risk patients. The nomogram showed good ability to predict survival time. And SIRT3, PIK3CA, ITGA3, DAPK1, and CASP3 increased in CRC group through the PCR assay.
Conclusion: Our study identified two distinct modes of anoikis in colorectal cancer, with active metastasis-promoting pathways inducing an anti-anoikis subtype, which has a stronger propensity for metastasis and a worse prognosis than an anoikis-activated subtype. Massive immune cell infiltration may be an indicator of anoikis resistance. Anoikis' role in the colorectal cancer remains to be investigated.
Keywords: Colorectal cancer, anoikis, signature, TME, prognostic model, drug predication
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