KIT Mutations Correlate with Higher Galectin Levels and Brain Metastasis in Breast and Non-Small Cell Lung Cancer

Funkhouser, Avery T.; Strigenz, Alexander M.; Blair, Bailey B.; Miller, Andrew; Shealy, Jonah C.; Ewing, Joseph A.; Martin, Julie P.; Funk, Christopher Ronald; Edenfield, William J.; Blenda, Anna V.

doi:10.3390/cancers14112781

Cited by 17 publications

(18 citation statements)

References 111 publications

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“…On the other hand, Hussain et al report on KIT mutations in more than 20% of mammary carcinoma biopsy samples, and most of these mutations have been detected before in other tumor types 42 . In another study Funkhouser et al found KIT mutations in more than 11% of investigated breast tumor samples and an association with serum galactin levels and occurrence of brain metastasis 43 . These observations suggest a role of KIT mutations in breast tumorigenesis or disease progression.…”

Section: Discussionmentioning

confidence: 96%

New C3H KitN824K/WT cancer mouse model develops late-onset malignant mammary tumors with high penetrance

Klein-Rodewald

Micklich²,

Sanz-Moreno³

et al. 2022

Sci Rep

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Gastro-intestinal stromal tumors and acute myeloid leukemia induced by activating stem cell factor receptor tyrosine kinase (KIT) mutations are highly malignant. Less clear is the role of KIT mutations in the context of breast cancer. Treatment success of KIT-induced cancers is still unsatisfactory because of primary or secondary resistance to therapy. Mouse models offer essential platforms for studies on molecular disease mechanisms in basic cancer research. In the course of the Munich N-ethyl-N-nitrosourea (ENU) mutagenesis program a mouse line with inherited polycythemia was established. It carries a base-pair exchange in the Kit gene leading to an amino acid exchange at position 824 in the activation loop of KIT. This KIT variant corresponds to the N822K mutation found in human cancers, which is associated with imatinib-resistance. C3H KitN824K/WT mice develop hyperplasia of interstitial cells of Cajal and retention of ingesta in the cecum. In contrast to previous Kit-mutant models, we observe a benign course of gastrointestinal pathology associated with prolonged survival. Female mutants develop mammary carcinomas at late onset and subsequent lung metastasis. The disease model complements existing oncology research platforms. It allows for addressing the role of KIT mutations in breast cancer and identifying genetic and environmental modifiers of disease progression.

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Section: Discussionmentioning

confidence: 96%

New C3H KitN824K/WT cancer mouse model develops late-onset malignant mammary tumors with high penetrance

Klein-Rodewald

Micklich²,

Sanz-Moreno³

et al. 2022

Sci Rep

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“…Several studies have indicated that KIT is associated with the development of lung cancer. For example, Funkhouser et al found KIT mutation is more likely to cause brain metastasis in NSCLC [ 66 ]. Zhou et al found targeting c-KIT can inhibit the growth and invasion of gefitinib-resistant NSCLC cells by reducing cancer stemness, EMT, and acquired drug resistance [ 67 ].…”

Section: Discussionmentioning

confidence: 99%

Exosomal hsa-miR-151a-3p and hsa-miR-877-5p are potential novel biomarkers for predicting bone metastasis in lung cancer

Zhao,

Jia,

Wang

et al. 2023

Aging

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Exosomal miRNAs (exo-miRNAs) have arisen as novel diagnostic biomarkers for various cancers. However, few reports on exo-miRNAs related to bone metastasis (BM) in lung cancer exist. This study aims to screen out key exo-miRNAs and estimate their prognostic values for predicting BM in lung cancer. The differentially expressed exo-miRNAs between the highly-metastatic (95D) and lowly-metastatic (A549) human lung cancer cell lines were comprehensively analyzed using high-throughput sequencing followed by bioinformatic analyses. 29 candidate exo-miRNAs were identified, and 101 BM-related target genes were predicted. Enrichment analysis revealed that these target genes were mainly involved in regulating transcription and pathways in cancer. An exosomal miRNA-mRNA regulatory network consisting of 7 key miRNAs and 10 hub genes was constructed. Further function analysis indicated that these 10 hub genes were mainly enriched in regulating cancer’s apoptosis and central carbon metabolism. The survival analysis indicated that 7 of 10 hub genes were closely related to prognosis. Mutation analysis showed that lung cancer patients presented certain genetic alterations in the 7 real hub genes. GSEA for a single hub gene suggested that 6 of 7 real hub genes had close associations with lung cancer development. Finally, ROC analysis revealed that hsa-miR-151a-3p and hsa-miR-877-5p provided high diagnostic accuracy in discriminating patients with bone metastasis (BM+) from patients without bone metastasis (BM-). These findings provided a comprehensive analysis of exo-miRNAs and target genes in the regulatory network of BM in lung cancer. In particular, hsa-miR-151a-3p and hsa-miR-877-5p may be novel biomarkers for predicting BM in lung cancer.

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“…This was approved by the Institutional Review Board of Prisma Health, Committee C on 05/30/2023 under 1949871-1 Use of Patient Data from the Prisma Health Center Biorepository for Molecular and Bioinformatics Analysis. The standard operating procedures of the PHCI biorepository have been described and acknowledged in multiple previous publications [ 27 , 28 , 29 , 30 ]. Among the patient samples, 49 consisted of adenocarcinoma and 38 of squamous cell carcinoma.…”

Section: Methodsmentioning

confidence: 99%

Exploratory Assessment of Galectin-1, -3, and -9 in Non-Small Cell Lung Cancer

Shuster,

Funkhouser,

Allen

et al. 2024

Cancers

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Galectins play a pivotal role in lung cancer oncogenic pathways, influencing apoptosis, angiogenesis, and tumor metastasis. Biomarkers that diagnose, prognose, and guide cancer treatment are crucial, with galectins having the biomarker potential for non-small cell lung cancer (NSCLC). Using enzyme-linked immunosorbent assay (ELISA), we assessed serum galectin-1, -3, and -9 levels in NSCLC patients. A retrospective chart review was performed to examine patient demographics, cancer stage, tumor biology, cancer treatment, and patient outcomes. Galectin levels were then compared across these factors. In this exploratory analysis, galectin-3 levels were significantly lower in patients with squamous cell lung cancer (p = 0.0019) and in patients exposed to chemotherapy (p = 0.0375). Galectin-1 levels were significantly lower in patients with previous metastasis but had no correlation with future metastasis. Abnormal galectin-1 levels were significantly correlated with decreased overall survival (OS) in NSCLC (p = 0.0357) and specifically in patients with surgically resectable NSCLC (p = 0.0112). However, abnormal galectin-1 levels were not found to correlate with decreased OS in multivariable analysis (p = 0.0513). These findings may have clinical implications as galectin-3 inhibitors are in trials for NSCLC. Additionally, they suggest that galectin-1 has potential as a prognostic marker for surgically resectable NSCLC.

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KIT Mutations Correlate with Higher Galectin Levels and Brain Metastasis in Breast and Non-Small Cell Lung Cancer

Cited by 17 publications

References 111 publications

New C3H KitN824K/WT cancer mouse model develops late-onset malignant mammary tumors with high penetrance

New C3H KitN824K/WT cancer mouse model develops late-onset malignant mammary tumors with high penetrance

Exosomal hsa-miR-151a-3p and hsa-miR-877-5p are potential novel biomarkers for predicting bone metastasis in lung cancer

Exploratory Assessment of Galectin-1, -3, and -9 in Non-Small Cell Lung Cancer

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