CTTN – Esophageal Squamous Cell Carcinoma

Recent genomic studies in esophageal squamous cell carcinoma (ESCC) have implicated alterations in CTTN as potential prognostic biomarkers. Two independent multi‐patient studies, one conducted in a Japanese cohort and another in African American patients, identified copy number alterations (CNAs) at chromosome 11q13.3 encompassing CTTN, with reported associations to progression-free survival that reached borderline and marginal significance (PMID:34962019) (PMID:34285259).

Clinical Validity

The overall clinical validity of the CTTN–ESCC association is rated as Moderate. This rating is based on evidence from two independent patient cohorts (127 patients (PMID:34962019) and 10 pairs (PMID:34285259)) that identified CNAs in CTTN. Although explicit segregation data are not available for a somatic malignancy, the consistent detection across studies supports its role in tumor progression.

Genetic Evidence

Genetic evidence stems from comprehensive whole-exome sequencing analyses in ESCC. Although specific HGVS variants were not detailed in the studies, the recurrent copy number alterations at 11q13.3—including CTTN—across two distinct populations suggest a moderate level of genetic evidence. This is bolstered by the integration of genomic alteration frequencies with clinical outcomes.

Functional and Experimental Evidence

Functional studies of CTTN provide mechanistic support for its role in ESCC. In vitro experiments have demonstrated that cortactin, the protein product of CTTN, regulates actin cytoskeletal dynamics, cell migration, and invasion—all processes critical for cancer metastasis (PMID:12952985). These data mechanistically align with the observed genomic alterations in patient tumors.

Integration & Conclusion

In summary, both genetic and functional evidence contribute to a coherent narrative where alterations in CTTN impact cellular behaviors relevant to ESCC progression. While the genetic findings report correlations that are borderline in statistical significance, the supportive experimental data on cortactin’s function in cell motility lend further biologic plausibility. No significant conflicting evidence was identified, reinforcing the potential utility of CTTN alterations as prognostic biomarkers.

Key Take‑Home Sentence

The integration of moderate genomic and functional evidence suggests that CTTN alterations represent a promising biomarker for prognosis in esophageal squamous cell carcinoma.

References

• Cancer science • 2022 • Prognostic biomarker study in patients with clinical stage I esophageal squamous cell carcinoma: JCOG0502-A1 PMID:34962019
• Scientific reports • 2021 • Exome sequencing identifies novel somatic variants in African American esophageal squamous cell carcinoma PMID:34285259
• The Journal of biological chemistry • 2003 • Alternative splicing of the actin binding domain of human cortactin affects cell migration PMID:12952985

Evidence Based Scoring (AI generated)