Somatic Mutation Profiling in the Liquid Biopsy and Clinical Analysis of Hereditary and Familial Pancreatic Cancer Cases Reveals KRAS Negativity and a Longer Overall Survival

Earl, Julie; Barreto, Emma; Castillo, María E.; Fuentes, R.; Rodríguez-Garrote, Mercedes; Ferreiro, Reyes; Reguera, Pablo; Muñoz, Gloria; García-Seisdedos, David; López, J. Villalón; Sáinz, Bruno; Malats, Núria; Carrato, Alfredo

doi:10.3390/cancers13071612

Cited by 4 publications

(2 citation statements)

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“…Pancreatic ductal adenocarcinoma (PDAC) is known for its resistance to traditional therapy, with a high percentage of recurrence and a poor five-year survival rate [ 1 ]. Recently, several reports revealed that PDAC are more vulnerable to ferroptosis inducers [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Activated Stellate Cell Paracrine HGF Exacerbated Pancreatic Cancer Cell Ferroptosis Resistance

Liu

Guo

et al. 2022

Oxidative Medicine and Cellular Longevity

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As a refractory tumor, pancreatic carcinoma is more vulnerable to ferroptosis, a novel regulated cell death mode. However, the exact role of pancreatic stellate cells (PSCs) in pancreatic cancer ferroptosis is still unclear. Using the coculture system, we revealed that activated PSCs promote pancreatic cancer cell ferroptosis resistance. Mechanistically, activated PSCs secreted HGF, which further activated the HGF receptor, c-MET, in pancreatic cancer cells, prevented lipid peroxidation, and ultimately triggered pancreatic cancer cell ferroptosis resistance in vitro and in vivo. TCGA and GEPIA databases also revealed a strong correlation between c-MET and antiferroptosis indicators. Our study supplied the evidence for the cross-talk between activated PSCs and pancreatic cancer cells in ferroptosis, which suggested a strategy to inhibit PSC paracrine signaling for preventing pancreatic carcinoma ferroptosis resistance.

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Section: Introductionmentioning

confidence: 99%

Activated Stellate Cell Paracrine HGF Exacerbated Pancreatic Cancer Cell Ferroptosis Resistance

Liu

Guo

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…The authors wish to make the following corrections to this paper [1]: In the published version, Figure 4 appeared as a duplication of Figure 1b. Furthermore, the legend of Figure 2 has been corrected to accurately reflect the data shown.…”

mentioning

confidence: 99%

Correction: Earl et al. Somatic Mutation Profiling in the Liquid Biopsy and Clinical Analysis of Hereditary and Familial Pancreatic Cancer Cases Reveals KRAS Negativity and a Longer Overall Survival. Cancers 2021, 13, 1612

Earl

Barreto

Castillo

et al. 2021

Cancers

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Bringing Hope to Improve Treatment in Pancreatic Ductal Adenocarcinoma—A New Tool for Molecular Profiling of KRAS Mutations in Tumor and Plasma Samples

Bravo,

Morão,

Luz

et al. 2024

Cancers

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Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) incidence is rising, and prognosis remains poor due to late diagnosis and limited effective therapies. Currently, patients are treated based on TNM staging, without molecular tumor characterization. This study aimed to validate a technique that combines the amplification refractory mutation system (ARMS) with high-resolution melting analysis (HRMA) for detecting mutations in codon 12 of KRAS in tumor and plasma, and to assess its prognostic value. Methods: Prospective study including patients with newly diagnosed PDAC with tumor and plasma samples collected before treatment. Mutations in codon 12 of KRAS (G12D, G12V, G12C, and G12R) were detected using ARMS–HRMA and compared to Sanger sequencing (SS). Univariate and multivariate analyses were used to evaluate the prognostic significance of these mutations. Results: A total of 88 patients, 93% with ECOG-PS 0–1, 57% with resectable disease. ARMS–HRMA technique showed a higher sensitivity than SS, both in tumor and plasma (77% vs. 51%; 25 vs. 0%, respectively). The most frequent mutation was G12D (n = 32, 36%), followed by G12V (n = 22, 25%). On multivariate analysis, patients with G12D and/or G12C mutations, either in tumor or plasma, had lower PFS (HR 1.792, 95% CI 1.061–3.028, p = 0.029; HR 2.081, 95% CI 1.014–4.272, p = 0.046, respectively) and lower OS (HR 1.757, 95% CI 1.013–3.049, p = 0.045; HR 2.229, 95% CI 1.082–4.594, p = 0.030, respectively). Conclusions: ARMS–HRMA is a rapid and cost-effective method for detecting KRAS mutations in PDAC patients, offering the potential for stratifying prognosis and guiding treatment decisions. The presence of G12D and G12C mutations in both tumor and plasma is associated with a poorer prognosis.

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Somatic Mutation Profiling in the Liquid Biopsy and Clinical Analysis of Hereditary and Familial Pancreatic Cancer Cases Reveals KRAS Negativity and a Longer Overall Survival

Cited by 4 publications

References 44 publications

Activated Stellate Cell Paracrine HGF Exacerbated Pancreatic Cancer Cell Ferroptosis Resistance

Activated Stellate Cell Paracrine HGF Exacerbated Pancreatic Cancer Cell Ferroptosis Resistance

Correction: Earl et al. Somatic Mutation Profiling in the Liquid Biopsy and Clinical Analysis of Hereditary and Familial Pancreatic Cancer Cases Reveals KRAS Negativity and a Longer Overall Survival. Cancers 2021, 13, 1612

Bringing Hope to Improve Treatment in Pancreatic Ductal Adenocarcinoma—A New Tool for Molecular Profiling of KRAS Mutations in Tumor and Plasma Samples

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