GKN1 – Lung Cancer Association

This summary provides a critical evaluation of the association between Gastrokine‑1 (GKN1, HGNC:23217) and lung cancer (MONDO_0008903). Multiple case‑control studies have interrogated GKN1 expression and polymorphism profiles in lung cancer patients. In one large‐scale transcriptomic analysis including 537 lung adenocarcinoma patients (PMID:27301951), dysregulated expression of GKN1 among several chromosome 2 genes was noted. Such findings indicate potential diagnostic relevance when compared to non‑cancer tissues.

Subsequent genetic association studies have focused on the GKN1 single nucleotide polymorphism rs4254535. In a study of 888 lung cancer patients, the recessive CC genotype was significantly associated with a better prognosis in subgroups such as females and late‑stage patients (PMID:38250608). An earlier investigation in a Chinese Han population also demonstrated that GKN1 variants correlate with altered chemotherapy response, reinforcing the gene’s prognostic potential (PMID:25999661).

Genetic evidence for the GKN1–lung cancer association is based solely on common polymorphism studies with no reported rare or high‑penetrance alleles, nor any classical family segregation data. As such, while multiple independent studies have reported statistically significant associations in large cohorts, the overall genetic evidence is limited.

Functional insights into GKN1 derive largely from studies in gastric cancer. Experimental assays have demonstrated that GKN1 expression modulates cell migration and invasion through regulation by miR‑548d‑3p (PMID:35666636); however, these findings are yet to be directly validated in lung cancer models. Therefore, functional evidence supporting its pathogenetic role in lung cancer remains indirect and limited.

In summary, although several independent studies support a role for GKN1 polymorphism rs4254535 as a prognostic marker in lung cancer, the association is currently classified as limited due to its reliance on association data without corroborative segregation or direct functional evidence in lung cancer. Further investigation, including mechanistic studies in lung cancer models, is needed to fully establish its clinical utility.

Key takeaway: GKN1 is a promising biomarker for risk stratification and prognosis in lung cancer, but additional targeted functional studies are required to confirm its mechanistic role.

References

• Cell biology and toxicology • 2016 • Variations of chromosome 2 gene expressions among patients with lung cancer or non‑cancer PMID:27301951
• Disease markers • 2015 • Polymorphisms in C‑reactive protein and Glypican‑5 are associated with lung cancer risk and Gartrokine‑1 influences Cisplatin‑based chemotherapy response in a Chinese Han population PMID:25999661
• International journal of medical sciences • 2024 • Significance of Gastrokine‑1 Polymorphism Rs4254535 as a Prognostic Marker and its Association with Clinical Characteristics in Chinese Lung Cancer Patients PMID:38250608
• Journal of clinical laboratory analysis • 2022 • miR‑548d‑3p inhibits the invasion and migration of gastric cancer cells by targeting GKN1 PMID:35666636

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