Research of cancer progression mechanisms and their impact on metabolism of tumor cells and tumor microenvironment cells is an important element in drug development for cancer target therapy. In this study, changes in tumor tissue and margin tissue lipid profiles, were associated with the following clinical and morphological characteristics: tumor size, cancer stage, multifocalite, tumor grade, number of lymph node metastasis, Nottingham prognostic index, total malignancy score, level of Ki67 protein. Lipid profiling was performed by reverse-phase chromato-mass spectrometry analysis of lipid tissue extract with lipid identification by characteristic fragments. In the lipid profile of tumor tissue 13 characteristic lipids were selected. Their levels significantly correlated with at least 5 clinical and morphological features. Eight of 13 belonged to phosphatidylcholines. In lipid profile of tumor microenviroment tissue 13 lipid features were selected. Their levels significantly correlated with at least 5 clinical and morphological features. Four of 13 belonged to oxidized lipids, 4 lipid features belonged to sphingomyelins, four of 13 belonged to phosphatidylethanolamines. The tumor microenvironment tissue lipid profile correlated with tumor size, cancer stage, tumor grade, number of axillary metastases, Nottingham prognostic index. The tumor tissue lipid profile correlated with tumor size, tumor grade, total malignant score, and number of axillary metastases.
Issledovanie mekhanizmov progressirovaniia raka, a takzhe vliianie opukholevoĭ progressii na metabolizm opukholevykh kletok i metabolizm kletok mikrookruzheniia opukholi iavliaetsia vazhnym élementom dlia razrabotki preparatov dlia tselevoĭ terapii raka. V dannoĭ rabote issledovali izmenenie lipidomnogo profilia opukholevykh tkaneĭ i pogranichnykh tkaneĭ opukholi, assotsiirovannoe so sleduiushchimi kliniko-morfologicheskimi kharakteristikami: razmer opukholi, stadiia raka, mul'tifokal'nost', stepen' differentsirovki opukholi, chislo uzlov, zatronutykh protsessom regionarnogo metastazirovaniia, Nottingemskiĭ prognosticheskiĭ indeks, summarnyĭ ball zlokachestvennosti, uroven' belka Ki67. Lipidnoe profilirovanie vypolneno pri pomoshchi obratno-fazovogo khromato-mass-spektrometricheskogo analiza lipidnogo ékstrakta tkaneĭ s identifikatsieĭ lipidov po kharakternym fragmentam. V opukholevoĭ tkani bylo vydeleno 13 lipidov, kotorye statisticheski znachimo korrelirovali ne menee chem s piat'iu kliniko-morfologicheskimi kharakteristikami. Vosem' iz 13 lipidov otnosilis' k klassu fosfatidilkholinov. V pogranichnoĭ tkani 13 lipidov statisticheski znachimo korrelirovali ne menee chem s piat'iu kliniko-morfologicheskimi kharakteristikami, kotorye otnosilis' k okislennym lipidam (4 soedineniia), sfingomielinam (4 soedineniia) i fosfatidilétanolaminam (4 soedineniia). Vyiavlena korreliatsiia lipidnogo profilia okruzhaiushchikh tkaneĭ (“opukholevoe pole”) s razmerom i stadieĭ opukholi, stepen'iu differentsirovki, chislom metastaticheskikh aksilliarnykh limfouzlov, Nottingemskim prognosticheskim indeksom. Lipidnyĭ profil' pervichnoĭ opukholi korreliroval s razmerom i stepen'iu differentsirovki opukholi, summarnym ballom zlokachestvennosti, chislom metastaticheskikh aksilliarnykh limfouzlov.
Keywords: breast cancer; cancer progression; lipidomics; mass-spectrometry; tumor microenvironment.