Small Cell Lung Cancer Therapeutic Responses Through Fractal Measurements: From Radiology to Mitochondrial Biology

Mambetsariev, Isa and Mirzapoiazova, Tamara and Lennon, Frances and Jolly, Mohit Kumar and Li, Haiqing and Nasser, Mohd W and Vora, Lalit and Kulkarni, Prakash and Batra, Surinder K and Salgia, Ravi (2019) Small Cell Lung Cancer Therapeutic Responses Through Fractal Measurements: From Radiology to Mitochondrial Biology. In: JOURNAL OF CLINICAL MEDICINE, 8 (7).

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Abstract

Small cell lung cancer (SCLC) is an aggressive neuroendocrine disease with an overall 5 year survival rate of similar to 7%. Although patients tend to respond initially to therapy, therapy-resistant disease inevitably emerges. Unfortunately, there are no validated biomarkers for early-stage SCLC to aid in early detection. Here, we used readouts of lesion image characteristics and cancer morphology that were based on fractal geometry, namely fractal dimension (FD) and lacunarity (LC), as novel biomarkers for SCLC. Scanned tumors of patients before treatment had a high FD and a low LC compared to post treatment, and this effect was reversed after treatment, suggesting that these measurements reflect the initial conditions of the tumor, its growth rate, and the condition of the lung. Fractal analysis of mitochondrial morphology showed that cisplatin-treated cells showed a discernibly decreased LC and an increased FD, as compared with control. However, treatment with mdivi-1, the small molecule that attenuates mitochondrial division, was associated with an increase in FD as compared with control. These data correlated well with the altered metabolic functions of the mitochondria in the diseased state, suggesting that morphological changes in the mitochondria predicate the tumor's future ability for mitogenesis and motogenesis, which was also observed on the CT scan images. Taken together, FD and LC present ideal tools to differentiate normal tissue from malignant SCLC tissue as a potential diagnostic biomarker for SCLC.

Item Type:	Journal Article
Publication:	JOURNAL OF CLINICAL MEDICINE
Publisher:	MDPI
Additional Information:	copyright for this article belongs to MDPI
Keywords:	small cell lung cancer; radiology; fractal dimension; lacunarity; mitochondria
Department/Centre:	Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited:	05 Sep 2019 11:55
Last Modified:	05 Sep 2019 11:55
URI:	http://eprints.iisc.ac.in/id/eprint/63496

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