Galectins are proteins with high-affinity β-galactoside-binding sites that function in a variety of signaling pathways through interactions with glycoproteins. The known contributions of galectins-1, -3, -7, -8, and -9 to angiogenesis, metastasis, cell division, and evasion of immune destruction led us to investigate the circulating levels of these galectins in cancer patients. This study compares galectin concentrations by enzyme-linked immunosorbent assay (ELISA) from each stage of breast, lung, and colon cancer. Galectins-1 and -7, which share a prototype structure, were found to have statistically significant increases in breast and lung cancer. Of the tandem-repeat galectins, galectin-8 showed no statistically significant change in these cancer types, but galectin-9 was increased in colon and lung cancer. Galectin-3 is the only chimera-type galectin and was increased in all stages of breast, colon, and lung cancer. In conclusion, there were significant differences in the galectin levels in patients with these cancers compared with healthy controls, and galectin levels did not significantly change from stage to stage. These findings suggest that further research on the roles of galectins early in disease pathogenesis may lead to novel indications for galectin inhibitors.

(1) Background: Endometriosis is characterized by the presence of endometrial glands and stroma outside of the uterus and is often associated with severe pelvic pain and infertility. Our study explored the utilization of B-Cell Lymphoma 6 (BCL6) and Sirtuin 1 (SIRT1) as potential biomarkers in serum, plasma, urine, and cervical mucus for a non-invasive diagnostic test for endometriosis. BCL6 was chosen based on its previously reported elevated expression in endometrial biopsies, and SIRT1 is co-expressed and upregulated in the endometrium of women with endometriosis. (2) Methods: BCL6 and SIRT1 levels were measured using enzyme-linked immunoassay (ELISA) in samples from 20 women with endometriosis (ten with stages I/II and ten with stages III/IV) and ten women without endometriosis. (3) Results: Levels of SIRT1 in sera showed a statistically significant elevation in advanced stages III/IV compared to controls and stages I/II. No significant differences were found in other bodily fluids for SIRT1 or any bodily fluids tested for BCL6. (4) Conclusions: These results suggest some potential of SIRT1 expression within serum as a predictor of advanced asymptomatic stages of endometriosis. Using immunohistochemistry (IHC) staining and H-SCORE values for the elevated BCL6 (and potentially SIRT1) levels in endometrial biopsy samples seems to have higher diagnostic potential based on the previously published studies.

To investigate a potential role for galectins as biomarkers that enable diagnosis or prognostication of breast or non-small cell lung cancer, the serum levels of galectins -1, -3, -7, -8, and -9 of cancer patients determined by ELISA assays were compared to the mutation status of 50 known cancer-critical genes, which were determined using multiplex PCR in tumors of the same patients. Mutations in the KIT proto-oncogene, which codes for the c-Kit protein, a receptor tyrosine kinase, correlated with higher levels of galectins -1, -3, -8, and -9 in breast cancer patients and galectin-1 in non-small cell lung cancer patients. Mutations in the KIT gene were more likely found in brain metastases from both of these primary cancers. The most common KIT mutation in our panel was p.M541L, a missense mutation in the transmembrane domain of the c-Kit protein. These results demonstrate an association between KIT oncogenic signaling and elevated serum galectins in patients with metastatic disease. Changes in protein trafficking and the glycocalyx composition of cancer cells may explain the observed alterations in galectin expression. This study can be useful for the targeted selection of receptor tyrosine kinase and galectin inhibitor anti-cancer treatments.

Background. Lung cancer is the leading cause of cancer-related death in both men and women in the United States. Non-small Cell Lung Cancer is the most prevalent and includes adenocarcinoma (AD), and squamous cell lung cancers. The unique cellular biology of these cancers could potentially allow for serological detection and identification via tissue specific protein markers. Galectins are a group of β-galactoside binding proteins which are known to be alternatively expressed in cancers and are being studied for their biomarker potential. Galectin-7 is expressed in epithelial tissues as well as in all layers of the epidermis as it is normally highly expressed by squamous cells. Purpose. We are evaluating potential of galectin-7 to be used as a serum biomarker and delineator of several lung cancer subtypes. Methods. The serum concentrations of galectin-7 were measured in 96 cancer patients using ELISA. Twenty-eight samples were from adenocarcinoma lung cancer patients, 25 were from squamous cell lung carcinomas patients, 19 were from all other types of lung cancer, and 28 were from other squamous cell carcinomas of non-pulmonary origin. The serum galectin-7 concentrations in cancer patients were compared amongst themselves by their histological subtypes. One-way analysis was performed using Student’s t-test for pairwise comparisons. Results. Galectin-7 concentrations were significantly elevated in serum samples from squamous cell lung cancer patients (n=25; mean, 1.91 ng/mL) relative to adenocarcinoma lung cancer patients (n=24; mean, 1.02; p-value, 0.0149). Additionally, levels of galectin-7 in samples of squamous cell lung carcinomas were higher than samples of squamous cell carcinomas of non-pulmonary origin (n=28; mean, 0.33 ng/mL, p-value, <0.0001). These results show that serum galectin-7 is increased in patients with squamous cell lung cancer compared to adenocarcinoma lung cancer. Conclusion. Potential clinical applications of this study include the measurement of galectin-7 in blood samples of cancer patients to aid in cancer screening and tumor type identification. Further explorations comprise measuring serum concentrations of galectin-7 by stage of squamous cell lung cancer and histological subtype (keratinizing, non-keratinizing, and basaloid) to determine a more nuanced understanding of the tumor molecular biology. Citation Format: Avery T. Funkhouser, Jonah C. Shealy, Alexandra E. Kesic, Bailey B. Blair, Julie C. Martin, Connie M. Arthur, Christopher R. Funk, W. Jeffery Edenfield, Anna V. Blenda. Potential of galectin-7 as differentiating biomarker of lung cancer subtypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2192.