Role of serum α-Klotho level in patients with breast carcinoma.
Authors: Melemadathil Karthika Remeshchandra , Udupa Karthik , Belle Vijetha Shenoy , K. Udupa Chethana Babu , Pai Ananth , Mailankody Sharada 
Published: June 2024

e15031 Background: The Klotho gene regulates multiple intracellular signalling pathways involving FGF-23, Insulin, IGF1, TGF-β1, Wnt/β-catenin and mammalian targets of rapamycin. The Klotho gene is downregulated in cancer and has a tumour suppressor role. Only a few studies have been done assessing its role in various cancers. None has looked into its association with all the clinicopathological characteristics of Carcinoma breast along with Pathological complete response (PCR). In August 2022, an oral senolytic form of Klotho was identified making it a possible and targetable protein. Methods: This was a Prospective cross-sectional study. Patients with biopsy-proven carcinoma breast who were previously untreated and had no significant past history were included. 84 patients were studied. Serum αKlotho level was estimated before initiating any treatment and its association with clinicopathological characteristics and with PCR was analysed. Results: A total of 84 patients were studied. The mean age was 50.76 years. Amongst our patients 65% were Estrogen Receptor (ER)+, 41.6% HER2+ and 11.9% were TNBC. 11.9% were of T1 stage, 29.8% T2, 19% T3, and 39.3% were T4. 16.7% had N0, 48.8% N1, 14.3% N2 and 20.2% had N3 stage. 20.2% were metastatic (MBC) and 79.8% were non-metastatic. 33.3% had grade 3 tumours, 56% grade 2 and 10.7% had grade 1. 61.9% were treated with NACT. The mean serum αKlotho level was 1.81ng/ml ranging from 0-5.15ng/ml. The αKlotho level was 2.04ng/ml in ER+ and 1.37ng/ml in ER-negative (p 0.011). As the Nottingham grade of the tumour increased from 1 to 3, αKlotho level decreased, with a mean value of 3.54ng/ml in grade 1, 1.71ng/ml in grade 2, and 1.42ng/ml in grade 3 (p 0.001). As the T stage increased from 1 to 4, αKlotho level decreased from 2.6ng/ml to 1.61ng/ml. Patients with N0 had a higher αKlotho of 2.92ng/ml, N1 had 1.64ng/ml, N2 1.79ng/ml, and N3 had 1.31ng/ml (p 0.001). MBC had a lower level of 1.47ng/ml than non-metastatic(1.9ng/ml). αKlotho level negatively correlated with ki67 with a correlation coefficient of -0.2. Among the patients who received NACT, we analysed 36 patients for the correlation with PCR. αKlotho level in patients who attained PCR was 1.58ng/ml and in those who did not attain PCR was 1.64ng/ml which was not significant. Conclusions: Klotho gene is identified to have a tumour suppressor role and its product αKlotho seems to have a protective role in Carcinoma breast. We found that patients with a higher serum αKlotho level had a lower histological grade(p 0.001) and a Node-negative (p 0.001) disease. Non-metastatic patients and patients with lower Ki 67 had high αKlotho levels. However, we could not find any significant association between αKlotho level and PCR. This is the first study with a large sample size done to look at the association of serum αKlotho with clinicopathological characteristics of carcinoma breast and that has found a significant association of αKlotho levels with higher grade and Node-negative disease.