Large-scale assessment of pros and cons of autopsy-derived or tumor-matched tissues as the norms for gene expression analysis in cancers

Sorokin, M.; Buzdin, A.A.; Guryanova, A.; Efimov, V.; Suntsova, M.V.; Zolotovskaia, M.A.; Koroleva, E.V.; Sekacheva, M.I.; Tkachev, V.S.; Garazha, A.; Kremenchutckaya, K.; Drobyshev, A.; Seryakov, A.; Gudkov, A.; Alekseenko, I.V.; Rakitina, O.; Kostina, M.B.; Vladimirova, U.; Moisseev, A.; Bulgin, D.; Radomskaya, E.; Shestakov, V.; Baklaushev, V.P.; Prassolov, V.; Shegay, P.V.; Li Xinmin; Poddubskaya, E.V.; Gaifullin, N.

Авторы: Sorokin Maksim, Buzdin Anton A., Guryanova Anastasia, Efimov Victor, Suntsova Maria V., Zolotovskaia Marianna A., Koroleva Elena V., Sekacheva Marina I., Tkachev Victor S., Garazha Andrew, Kremenchutckaya Kristina, Drobyshev Aleksey, Seryakov Aleksander, Gudkov Alexander, Alekseenko Irina V., Rakitina Olga, Kostina Maria B., Vladimirova Uliana, Moisseev Aleksey, Bulgin Dmitry, Radomskaya Elena, Shestakov Viktor, Baklaushev Vladimir P., Prassolov Vladimir, Shegay Petr V., Li Xinmin, Poddubskaya Elena V., Gaifullin Nurshat
Журнал: Computational and Structural Biotechnology Journal
Номер: 8
Год издания: 2023
Первая страница: 1
Последняя страница: 59
DOI: 10.1016/j.csbj.2023.07.040
Аннотация: AbstractNormal tissues are essential for studying disease-specific differential gene expression. However, healthy human controls are typically available only in postmortal/autopsy settings. In cancer research, fragments of pathologically normal tissue adjacent to tumor site are frequently used as the controls. However, it is largely underexplored how cancers can systematically influence gene expression of the neighboring tissues. Here we performed a comprehensive pan-cancer comparison of molecular profiles of solid tumor-adjacent and autopsy-derived “healthy” normal tissues. We found a number of systemic molecular differences related to activation of the immune cells, intracellular transport and autophagy, cellular respiration, telomerase activation, p38 signaling, cytoskeleton remodeling, and reorganization of the extracellular matrix. The tumor-adjacent tissues were deficient in apoptotic signaling and negative regulation of cell growth including G2/M cell cycle transition checkpoint. We also detected an extensive rearrangement of the chemical perception network. Molecular targets of 32 and 37 cancer drugs were over- or underexpressed, respectively, in the tumor-adjacent norms. These processes may be driven by molecular events that are correlated between the paired cancer and adjacent normal tissues, that mostly relate to inflammation and regulation of intracellular molecular pathways such as the p38, MAPK, Notch, and IGF1 signaling. However, using a model of macaque postmortal tissues we showed that for the 30 minutes – 24-hour time frame at 4ºC, an RNA degradation pattern in lung biosamples resulted in an artifact “differential” expression profile for 1140 genes, although no differences could be detected in liver. Thus, such concerns should be addressed in practice.Graphical abstract Download : Download high-res image (175KB) Download : Download full-size imageKeywordsCancer researchmolecular pathologyautopsytumor matched pathologically normal tissueshealthy tissue controlsdifferential gene expression analysisRNA sequencingmolecular pathways
Добавил в систему: Гайфуллин Нуршат Минуллаевич

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Large-scale assessment of pros and cons of autopsy-derived or tumor-matched tissues as the norms for gene expression analysis in cancersстатья

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