The First Multiomics Association Study of Trace Element and Mineral Concentration and RNA Sequencing Profiles in Human Cancers

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Arsenia O. Alekseeva¹, Marianna A. Zolotovskaia¹, Maksim I. Sorokin¹, Maria V. Suntsova¹, Galina S. Zakharova¹, Polina A. Pugacheva¹, Aleksey A. Tinkov², Tatiana V. Korobeinikova², Marina I. Sekacheva¹, Elena V. Poddubskaya^1,3, Anatoly V. Skalny², Nikolay E. Kushlinskii⁴, Anton A. Buzdin^1,5,6,a*

¹Digital Biodesign and Personalized Healthcare Research Center, Sechenov University, 119991 Moscow, Russia

²Center of Bioelementology and Human Ecology, Sechenov University, 119435 Moscow, Russia

³Vitamed Clinic, 117312 Moscow, Russia

⁴Blokhin National Medical Research Center of Oncology, 115478 Moscow, Russia

⁵Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, Russia

⁶PathoBiology Group, European Organization for Research and Treatment of Cancer (EORTC), Brussels, Belgium

^* To whom correspondence should be addressed.

Received: October 14, 2024; Revised: November 11, 2024; Accepted: November 12, 2024

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Integration of various types of omics data is an important trend in contemporary molecular oncology. In this regard, high-throughput analysis of trace and essential elements in cancer biosamples is an emerging field that has not yet been sufficiently addressed. For the first time, we simultaneously obtained gene expression profiles (RNA sequencing) and essential and trace element profiles (inductively coupled plasma mass spectrometry) for a set of human cancer samples. The biosamples were formalin-fixed, paraffin-embedded primary tumor tissue blocks: 67 for colorectal cancer patients and 18 for other solid cancer types (16 types). Mass spectrometry profiles were obtained for 45 chemical elements: Ag, Al, As, Au, B, Ba, Be, Bi, Ca, Cd, Co, Cr, Cu, Fe, Ga, Ge, Hg, I, K, La, Li, Mg, Mn, Mo, Na, Ni, P, Pb, Pd, Pt, Rb, Sb, Sc, Se, Si, Sn, Sr, Te, Ti, Tl, Zn, U, V, W, and Zr. The expression levels were profiled for 36,596 known human genes, and the activation levels were assessed for 10,520 human intracellular molecular pathways. For the concentrations of essential elements Ca, Cu, Fe, K, Mg, Na, P, and Zn we detected statistically significant correlations on both gene expression and pathway activation levels for both colorectal cancer samples and at the pan-cancer level. In total, 222/137, 122/220, 1/0, 239/186, 71/44, 1/0, 354/294, 69/82 gene/pathway biomarkers were detected for Ca, Cu, Fe, K, Mg, Na, P, and Zn, respectively. We believe that this first-in-class database provided here will be valuable for multiomics cancer research.

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KEY WORDS: colorectal cancer, human solid cancers, trace elements, inductively coupled plasma mass spectrometry, RNA sequencing, gene expression, intracellular molecular pathway, pathway activation level

DOI: 10.1134/S0006297924120150

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