Impact of Cuproptosis-Related Genes on Pancreatic Cancer

Overview of Cuproptosis and Its Role in Cancer Progression

Cuproptosis is an emerging mechanism of cell death associated with copper overload, characterized by the selective binding of copper to lipid acylated proteins in the tricarboxylic acid (TCA) cycle. This interaction induces acute proteotoxic stress, leading to mitochondrial dysfunction and ultimately cell death (Wang et al., 2022). The significance of cuproptosis in cancer is underscored by the fact that copper, an essential trace element, plays vital roles in various cellular functions, including growth and metabolism. However, the dysregulation of copper homeostasis has been implicated in the pathogenesis of several cancers, including pancreatic cancer.

Pancreatic cancer is notorious for its poor prognosis and high mortality rates, often attributed to late-stage diagnosis and aggressive tumor behavior. The recent discovery of cuproptosis links copper metabolism to the malignant transformation and progression of pancreatic cells, suggesting that targeting cuproptosis-related pathways could offer new therapeutic strategies. Recent studies have indicated that cuproptosis may provide a novel target for cancer therapies, particularly for pancreatic cancer, as it is associated with altered cellular metabolism and stress responses in neoplastic tissues (Deng et al., 2025).

In the context of pancreatic cancer, several cuproptosis-related genes (CRGs) have been identified that play crucial roles in tumor progression and patient prognosis. A comprehensive analysis utilizing TCGA and GTEx databases revealed 16 CRGs, from which five key genes were selected based on their association with overall survival (OS) in pancreatic cancer patients: PDP1, DLAT, DBT, LIAS, and LIPT1 (Deng et al., 2025). These genes were found to be significantly upregulated in pancreatic cancer tissues compared to normal pancreatic tissues, indicating their potential oncogenic roles.

The prognostic model developed from these five CRGs demonstrated that patients categorized into high-risk groups based on their expression profiles had poorer survival outcomes. Specifically, the risk score model indicated that high-risk patients had a significantly shorter OS, with notable implications for clinicopathological features such as age and N stage (Deng et al., 2025). This highlights the potential of CRGs as biomarkers for risk stratification and therapeutic targeting in pancreatic cancer.

Gene	Hazard Ratio (HR)	p-value
PDP1	1.57	0.033
DLAT	1.60	0.027
DBT	1.90	0.0021
LIAS	1.68	0.014
LIPT1	1.95	0.0013

The prognostic evaluation of the five identified CRGs was conducted using univariate and multivariate Cox regression analyses. The results indicated that age, N stage, and the calculated risk score were significant independent prognostic indicators for pancreatic cancer (Deng et al., 2025). The establishment of a prognostic model utilizing these CRGs allows for improved prediction of patient outcomes and may inform treatment decisions, highlighting the necessity for early intervention in high-risk populations.

Table 2: Multivariate Cox Regression Analysis of Prognostic Factors

Factor	Hazard Ratio (HR)	p-value
Age	1.05	< 0.001
N Stage	2.10	< 0.001
Risk Score	1.82	< 0.001

The application of decision curve analysis (DCA) further confirmed the utility of the CRG-based model, demonstrating a net clinical benefit for patients classified as high risk for adverse outcomes. This model outperformed traditional clinicopathological factors, emphasizing its relevance in clinical practice.

Immune Infiltration and Its Relationship with Cuproptosis Genes

The tumor microenvironment (TME) plays a crucial role in cancer progression, and immune cell infiltration is a key component of the TME. Utilizing the ESTIMATE algorithm and the CIBERSORT method to analyze immune cell populations, significant differences in immune infiltration were observed between high-risk and low-risk patients (Deng et al., 2025). Specifically, patients in the low-risk group showed higher levels of CD4+ memory T cells and mast cells, indicating a more favorable immune profile that may contribute to better clinical outcomes.

Table 3: Immune Cell Composition in High-Risk vs. Low-Risk Groups

Immune Cell Type	High-Risk %	Low-Risk %
CD4+ Memory T Cells	15	25
CD8+ T Cells	10	18
B Cells	5	12
Mast Cells	4	10

The correlation between CRGs and immune infiltration suggests that these genes may influence not only tumor biology but also the immune landscape in pancreatic cancer, providing insights into potential therapeutic strategies that could enhance immune responses against tumors.

Implications of Emotional Eating and BMI on Cancer Outcomes

The interplay between body mass index (BMI), emotional eating, and cancer outcomes has gained attention in the context of chronic disease management. Emotional eating, characterized by consuming food in response to emotional distress, has been linked to higher BMI and associated comorbidities, including diabetes and cardiovascular diseases (Ljubičić et al., 2025). This pattern is particularly concerning in cancer patients, where obesity may exacerbate treatment outcomes and survival rates.

Table 4: Association of Emotional Eating with BMI and NCDs

Emotional Eating Behavior	BMI ≥ 25 (Odds Ratio)	NCDs (Odds Ratio)
Eating to Cope with Stress	1.31	2.18
Eating for Emotional Consolation	1.22	1.50
Eating Out of Boredom	1.11	1.10

The findings suggest that addressing emotional eating behaviors in conjunction with BMI management could play a vital role in improving health outcomes for cancer patients. Integrative approaches that encompass psychological support, nutritional counseling, and physical activity promotion are essential for managing weight and enhancing the quality of life among these patients.

Conclusion

In conclusion, the investigation of cuproptosis-related genes offers significant insights into the biology of pancreatic cancer, with potential implications for prognosis and treatment. The identification of key CRGs, their prognostic value, and their relationship with immune infiltration underscore the importance of targeting these pathways in therapeutic strategies. Moreover, the interplay of emotional eating, BMI, and noncommunicable diseases highlights the multifaceted nature of cancer management, necessitating a holistic approach that considers psychological and nutritional aspects. Future studies aimed at elucidating the mechanistic roles of CRGs and integrated lifestyle interventions will be crucial in advancing the care of patients with pancreatic cancer.

FAQs

What is cuproptosis?
Cuproptosis is a form of programmed cell death induced by copper overload, leading to proteotoxic stress and mitochondrial dysfunction.

How do cuproptosis-related genes (CRGs) affect pancreatic cancer?
CRGs play significant roles in the progression and prognosis of pancreatic cancer, with specific genes identified as potential biomarkers for survival outcomes.

What are the implications of emotional eating for cancer patients?
Emotional eating can lead to increased BMI and associated health issues, potentially worsening cancer outcomes. Addressing these behaviors is crucial for effective cancer management.

Why is immune infiltration important in cancer?
Immune infiltration in tumors can influence treatment responses and prognosis. Understanding the immune landscape helps to develop targeted therapies that enhance immune responses against cancer.

What future directions does this research suggest?
Future studies should focus on elucidating the mechanisms of CRGs in cancer, as well as integrating lifestyle interventions that address emotional eating and BMI management for improved patient outcomes.

References

Deng, Q., Yang, K., Liao, Q., Tang, X., Quan, H., & Wu, L. (2025). Comprehensive analysis and experiment validation of five cuproptosis-related genes in prognosis, immune infiltration and metabolic characterization of pancreatic cancer. PLOS ONE. https://doi.org/10.1371/journal.pone.0323458
Wang, Y., Zhang, L., Zhou, F. (2022). Cuproptosis: a new form of programmed cell death. Cellular & molecular immunology. https://doi.org/10.1038/s41423-022-00866-1
Ljubičić, M., Matek Sarić, M., Sorić, T., Klarin, I., Dželalija, B., & Guiné, R. (2025). The interplay between body mass index, motivation for food consumption, and noncommunicable diseases in the European population: A cross-sectional study. PLOS ONE. https://doi.org/10.1371/journal.pone.0322454