SEPTIN9 (Septin 9)

By integrating structural, cellular, and energetic readouts using in-silico techniques, we establish a quantitative framework for septin-targeted modulation, generating UR214-9 as a new chemotype that disrupts septin oligomeric assembly via preventing incorporation of SEPT2/7/9, into canonical hetero-octamers, causes defects in cytokinesis, altered cell migration, viability, and remodels septin-actin architectures, ultimately impairing tumor cell growth. Thus, pharmacological targeting of septin assembly represents a tractable strategy to perturb septin-dependent cellular processes in cancer and neurodegenerative diseases with reported septin dysregulation.

The two-gene panel of SEPT9 and SPG20 represents a highly sensitive and specific non-invasive biomarker combination for CRC detection. However, these preliminary findings should be interpreted with caution given the small sample size and require validation in larger, independent screening cohorts before clinical implementation.

Heterogeneity and geographical concentration may influence the assessment of mSEPT9. www.crd.york.ac.uk/prospero identifier is CRD420251140125.

Updated guidelines for standardized implementation are also crucial. This review underscores the pivotal role of methylation biomarkers to revolutionize screening of CRC, while stressing the need for interdisciplinary collaboration, and outlines a strategy to address current limitations, ultimately aiming to reduce the global impact of CRC.

The findings are highly robust across sensitivity analyses. This study supports the updated recommendation to lower the CRC screening initiation age for average-risk individuals and identifies annual FIT screening as the optimal strategy in the current context of China.

Among lesions with initially indeterminate histology, 88.24% (15/17) of SEPT9-positive cases were later confirmed to be urothelial carcinoma (UC), compared to only 4.55% (1/22) of negative cases. These findings indicate that SEPT9 methylation is a promising adjunct to histopathology that can distinguish benign from neoplastic lesions and uncover latent malignancies in morphologically ambiguous flat urothelial lesions.

Combination with CEA and CA19-9 could improve its performance. It may serve as a viable alternative for individuals unwilling or unable to undergo invasive procedures.

For genes examined in at least two papers, we summarized the reported accuracy measurements by presenting the average, minimum, and maximum values for each CpG group. This scoping review identifies a profound lack in the reporting of the CpG sites analyzed for non-invasive detection of CRC, which poses a challenge for the comparison of findings across studies.

This study establishes a minimally invasive, peripheral blood DNA methylation-based detection method for GC screening. The model demonstrates robustness, high sensitivity, and specificity, offering an effective strategy for population-level screening. The primary limitations of this study include the relatively small size of the validation cohort and a significant imbalance in TNM stage distribution. Additionally, there is a potential limitation in accurately discriminating gastric cancer risk within high-risk precancerous populations based solely on the current model. It is necessary to formulate a larger-scale prospective verification plan in the future.

In this study, SEPT9 overexpression was shown to contribute to the oncogenic phenotype of bladder cancer and could serve as a potential early-stage biomarker. Moreover, SEPT9 may offer new avenues for developing more effective targeted therapeutic approaches for bladder cancer. Future studies addressing this aspect will be important for better defining the role of SEPT9 across diverse bladder cancer contexts.

The mSEPT9 can be used as a sensitive and efficient indicator for CRC diagnosis and surgical efficacy evaluation, outperforming both CEA and CA19-9. A combined panel of mSEPT9, CEA, and CA19-9 was shown to achieve superior diagnostic performance compared to mSEPT9 alone. More significantly, our findings highlight the significant value of mSEPT9 in monitoring postoperative recurrence and metastasis in CRC patients. Specifically, mSEPT9 detection at one month after surgery could be an independent predictor, capable of predicting the recurrence or metastasis of CRC.

We developed and validated two ML-based models integrating Septin9 methylation with routine serum biomarkers for early detection and differentiation of CRC. These models show potential as non-invasive clinical decision-support tools to facilitate individualized risk assessment and support clinical management in patients undergoing evaluation for colorectal neoplasia.