Liquid biopsies amfani da jini-ba tumo nama - don gano asibiti ciwon daji
Yawanci, ana yin nazarin ciwon sukari ta hanyar amfani da kwayoyin halitta. Ana daukar ƙananan samfurin daga ƙwayar cutar da kwayar cutar, ko kuma aka yi nazarin kwayoyin halitta. Matsalar ta wannan hanya ita ce, ciwon daji na biopsying zai iya zama kalubale. Bugu da ƙari kuma, kwayar cutar ta jiki ba ta samar da hoto ne kawai ba.
Rubuta a cikin Magungunan Bincike a shekara ta 2015, Labgaa da co-marubuta sun furta wadannan abubuwa game da kwayoyin halittun tumo:
Don dalilai masu ma'ana, yana da wuyar saka idanu akan juyin halitta ta hanyar kwayoyin halitta. Har ila yau, biopsy kawai yana nuna guda ɗaya daga cikin kututture kuma sabili da haka ba zai yiwu ya wakilci dukan jinsin maye gurbi a cikin babban ciwon sukari ba. Wani zabi zai kasance don samo kwayoyin biopsies masu yawa don ƙwayar wannan ƙwayar, amma wannan zaɓi ba zai yiwu ba kuma ba daidai bane.
Liquid biopsy ya shafi jiyya na DNA (ctDNA) da kuma sauran ƙwayoyin cutar tumo a cikin samfurori da aka samu daga marasa lafiya da ciwon daji. Wannan tsarin bincike na yaduwa ya yi alkawalin cewa ya zama mai sauri, ba tare da komai ba, kuma yana da amfani.
Tarihin Labaran Liquid Biopsy
A 1948, Mandel da Métais, wasu masu bincike na Faransa sun fara gano ctDNA a cikin jinin mutanen lafiya. Wannan binciken ya kasance kafin lokacinsa, kuma ba har shekarun da dama bayan haka an kara bincikar ctDNA ba.
A shekarar 1977, Leon da abokan aiki sun gano cewa yawancin ctDNA a cikin jinin marasa lafiya.
A shekara ta 1989, Stroun da abokan aiki sun gano alamomi (watau ciwon daji) a cikin jini. Bayan wadannan binciken, wasu kungiyoyi sun gano ƙayyadaddun ƙwayoyin cuta a cikin masu ciwon tumo da ƙwayoyin ƙwayoyin ƙwayoyin cuta, rashin zaman lafiyar microsatellite, da kuma DNA methylation, wanda ya tabbatar da cewa ctDNA an sake shi cikin ƙwayoyin cutar da ciwon sukari.
Kodayake mun sani cewa ctDNA da aka samo daga kwayoyin tumatus ke gudana a cikin jini, asalin, ragowar saki, da kuma tsarin sakin wannan DNA ba su da tabbas, tare da binciken da ya haifar da sakamakon rikice-rikice. Wasu bincike sun nuna cewa ƙwayar cutar ciwon daji ke dauke da ƙwayoyin cututtuka da yawa kuma sun saki ctDNA. Duk da haka, wasu bincike sun nuna cewa dukkanin sutura na saki ctDNA. Duk da haka, yana da alama cewa ƙwayar cutar ciwon ƙwayar cuta ta karu da ƙwayar ctDNA a cikin jini, ta hanyar yin ctDNA mai kyau biomarker na ciwon daji.
Saboda matsananciyar raguwa da ƙananan ƙananan jini, ctDNA yana da wuya a ware da kuma bincika. Akwai bambanci na ƙwayar ctDNA tsakanin sutura da ƙwayoyin plasma. Yau da cewa jinin jini maimakon plasma jini shine mafi mahimmanci na ctDNA. A cikin wani binciken da Umetani da abokan aiki suka yi, an samu cibiyoyin ctDNA su zama marasa ƙarfi a cikin plasma idan aka kwatanta da magani saboda yiwuwar hasara na DNA a lokacin tsarkakewa, kamar yadda aka kawar da haɗin gwiwar da sauran sunadarai yayin shirya gwaji.
A cewar Heitzer da abokan aiki, ga wasu wasu matsalolin da ke buƙatar magance yiwuwar ganewar ctDNA:
Na farko, hanyoyin da ake amfani da su gaba ɗaya suna bukatar a daidaita su .... Zaɓin hanyar da ba za a raba ba wanda ya tabbatar da isasshen adadin yawan DNA mai mahimmanci yana da muhimmanci kuma an nuna shi cewa ka'idodin preanalytical na samfur samfurin da aiki zai iya tasiri sosai ga sakamakon DNA .... Abu na biyu, daya daga cikin mahimman al'amurra shi ne rashin daidaituwa da hanyoyi masu yawa. Hanyoyi masu rarraba daban-daban, ... samar da sakamako daban-daban saboda wadannan ma'aunai suna daukan nau'in DNA ne kawai ko kawai mai karfi. Na uku, an sani game da asali da kuma tsarin da aka saki na ctDNA, kuma a cikin yawancin nazarin da ya kunsa abubuwan da zasu iya taimakawa wajen sakin ctDNA.
An yi la'akari da vs. Abubuwan da ba a Gina ba
A halin yanzu, akwai manyan hanyoyi guda biyu da aka dauka yayin nazarin cutar jini (ko magani) don ctDNA. An samo asali na farko da nema don nuna bambancin kwayoyin da ke nuna magungunan ciwon daji. Ƙaƙiri na biyu ba shi da daidaituwa kuma yana dauke da bincike mai zurfi na mutum don neman ctDNA na nuna ciwon daji. A madadin haka, an yi amfani da jerin samfurori a matsayin mafi yawan kudin, wanda bai dace ba. Sakamakon su ne rabo daga DNA wanda aka rubuta don yin furotin.
Tare da hanyoyi da aka yi niyya, ana nazarin magani don sanin maye gurbin kwayoyin halitta a cikin ƙananan ƙwayoyin direbobi.
Sakamakon gyaran motsa jiki yana nufin maye gurbi a cikin kwayar da ke inganta, ko "drive," ci gaban ciwon daji. Wadannan maye gurbin sun haɗa da KRAS ko EGFR .
Saboda ci gaba da fasaha a cikin 'yan shekarun nan, hanyoyin da ake nufi da nazarin kwayar halitta don ƙananan ctDNA sun zama mai yiwuwa. Wadannan fasahar sun hada da ARMS (tsarin maye gurbin ƙarfin); PCR na dijital (dPCR); beads, emulsions, amplification, da magnetics (BEAMing); da kuma zane-zane mai zurfi (CAPP-Seq).
Ko da yake akwai ci gaba a fasahar da za ta yiwu manufa ta yiwu, ƙaddamar da manufar kawai tana ɗaukar wasu matsayi na maye gurbin (ƙwallon ƙafa) kuma ya rasa yawancin maye gurbin kamfanoni irin su kwayoyin cutar tumo.
Babban amfani da hanyoyin da ba su dace ba ga biopsy ruwa shine cewa za'a iya amfani da su a duk marasa lafiya saboda gaskiyar cewa gwajin ba ta dogara ne akan sauye-sauyen kwayoyin canji ba. Sauye-sauyen maye gurbin kwayoyin halitta ba ya rufe dukkan maycers kuma ba takamaiman sa hannu ba. Duk da haka, wannan hanyar ba ta da hankali sosai da nazarin kwayoyin tumo ba har yanzu ba tukuna.
Daga bayanin kula, farashin sakin kwayar halitta duka kwayar halitta ta daɗaɗa. A shekara ta 2006, farashin squencing dukan genome ya kimanin $ 300,000 (USD). A shekara ta 2017, farashin ya ragu zuwa kimanin $ 1,000 (USD) ta kowane hali, ciki har da masu haɓaka da kuma amortization na na'urori masu sassauki.
Amfani na asibiti na Liquid Biopsy
Ƙoƙarin ƙoƙari don amfani da ctDNA an gano su kuma idan aka kwatanta da matakan marasa lafiyar marasa lafiya da waɗanda ke fama da ciwon daji ko wadanda ke da cutar marasa lafiya. Sakamakon wannan kokarin da aka hade, tare da wasu binciken da ke nuna manyan bambance-bambance da ke nuna ciwon daji, halin rashin lafiya, ko sake dawowa.
Dalilin da yasa za'a iya amfani da ctDNA kawai daga lokacin da za a gwada ciwon daji saboda saboda yawancin ctDNA an samo daga ciwace-ciwacen ƙwayoyi. Ba dukkanin kwayar cutar "DNA" ba ne a cikin adadin. Bugu da ƙari, ci gaba da ci gaba, ciwon sukari da yawa ya sa ƙarin DNA a cikin wurare dabam dabam fiye da farkon, ganowa, ciwace-ciwacen ƙwayoyi. Bugu da ƙari, nau'o'in nau'in tumatir suna ba da DNA mai yawa a cikin wurare dabam dabam. Sashi na rarraba DNA wanda aka samo daga kwayar cutar yana iya canzawa a kowane nazari da nau'in ciwon daji, daga kashi 0.01% zuwa 93%. Yana da mahimmanci a lura cewa, a gaba ɗaya, kawai ƙananan 'yan tsiraru na ctDNA na samuwa ne daga ƙwayar cuta, sauran kuma yana fitowa ne daga nau'in ƙwayar jiki.
Za'a iya amfani da DNA ta hanyar rarraba DNA a matsayin alamaccen alamar cutar. Za'a iya amfani da DNA mai yadawa don saka idanu canje-canje a ciwon daji a tsawon lokaci. Alal misali, binciken daya ya nuna cewa yawan shekaru biyu na rayuwa a marasa lafiya da ciwon daji (watau adadin marasa lafiya har yanzu yana da rai a kalla shekaru biyu bayan ganewar asali tare da ciwon daji) da KRAS maye gurbin su kashi 100 cikin wadanda ba tare da shaidar Daidaitan watsa DNA. Bugu da ƙari, yana yiwuwa cewa a nan gaba, ana iya amfani da DNA mai rarraba don saka idanu da raunuka.
Za'a iya amfani da kwayar DNA mai mahimmanci don saka idanu ga maganin farfadowa. Saboda yaduwar DNA yana nuna hoto mafi kyau na tsarin kwayoyin cutar ciwon daji, wannan DNA yana iya ƙunshe da DNA bincike, wanda za'a iya amfani dashi maimakon bincike na DNA da aka samu daga ciwace-ciwacen da kansu.
Yanzu, bari mu dubi wasu takamaiman misalai na ruwa biopsy.
Guardant360
Ma'aikatar Tsaro ta ci gaba da gwajin da ke amfani da tsarawar tsara ta gaba zuwa bayanin da ke rarraba DNA don maye gurbin da sake dawowa na chromosomal domin kwayoyin cutar kanjamau 73. Ma'aikatar Tsaro ta wallafa wani binciken da ke bayar da rahotanni game da yadda ake amfani da kwayar halitta a cikin ilimin halittu. Nazarin yayi amfani da samfurorin jini daga marasa lafiya 15,000 tare da hade iri iri 50.
Ga mafi yawancin, sakamakon daga gwajin kwayoyin halitta da ke tattare da gyare-gyare na gine-gine a cikin kwayoyin halittun tumo.
A cewar NIH:
Guardant360 sun gano irin wannan canji mai mahimmanci a cikin manyan kwayoyin cutar kanjamau kamar EGFR, BRAF, KRAS , da kuma PIK3CA a daidai lokacin da aka gano su a cikin kwayoyin halittun tumatir na tumɓuke, wanda ya danganta da kashi 94% zuwa 99%.
Bugu da ƙari kuma, bisa ga NIH masu binciken sun ruwaito wannan:
A wani bangare na biyu na binciken, masu bincike sun kimanta kusan marasa lafiya 400 - yawancin su na da ciwon huhu ko ciwon daji - wanda ke da jini da ctDNA da ciwon nama na DNA yana samuwa kuma idan aka kwatanta da alamomin canji na kwayoyin. Daidaitaccen daidaitattun kwayoyin ruwa da aka kwatanta da sakamakon daga nazarin kwayoyin biopsy ya zama 87%. Daidaitawa ta karu zuwa 98% lokacin da aka tara jini da kyamaran samfurori cikin watanni 6 da juna.
Guardant360 ya kasance daidai ko da yake matakan yada DNA cikin jini basu da yawa. Sau da yawa, rarraba kwayar cutar DNA kawai ya zama kashi 0.4 na DNA cikin jini.
Bugu da ƙari, ta amfani da kwayar halitta ta ruwa, masu bincike na Guardance sun iya gano alamun tumo wanda zai iya jagorancin likita daga kashi 67 cikin 100 na marasa lafiya. Wadannan marasa lafiya sun cancanci maganin jiyya na FDA da magungunan bincike.
CtDNA da Ciwon Cutar Lung
A shekara ta 2016, FDA ta amince da gwajin gwajin EGFR na cobas da za a yi amfani dashi don ganowar maye gurbin EGFR a cikin DNA masu rarraba da marasa lafiya da ciwon huhu. Wannan jarrabawar ita ce ta farko da aka yarda da ita ta FDA da kuma gano marasa lafiya wadanda zasu iya zama masu neman magani don magance cutar ta hanyar amfani da erlotinib (Tarceva), afatinib (Gilotrif), da kuma gefitinib (Iressa) a matsayin magani na farko, da osimeritinib (Tagrisso) yin magani na biyu. Wadannan hanyoyin magance cutar kanjamau tare da wasu maye gurbin EGFR .
Abu mai mahimmanci, saboda yawan adadin sakamako na ƙarya-bakon, FDA ya bada shawarar cewa an cire samfurin biopsy na nama daga mai ciwon da ke da kwayar cutar ta cikin ruwa.
CtDNA da Cancer Cancer
Yawan mutanen da ke fama da cutar ciwon hanta sun karu a cikin shekaru 20 da suka gabata. A halin yanzu, ciwon daji ne shine abu na biyu da ya haifar da mutuwar ciwon daji a duniya. Babu mai kyau masu kare rayuka don ganowa da kuma nazarin hanta, ko hepatocellular (HCC), ciwon daji. Tsarin DNA zai iya zama mai kyau biomarker don ciwon huhu.
Ka yi la'akari da zantuttukan nan daga Lagbaa da masu marubuta game da yiwuwar yin amfani da DNA don rarraba cutar ciwon huhu:
An kwatanta hypermethylation na RASSF1A, p15, da p16 a matsayin kayan bincike na farko a cikin nazarin nazari da suka hada da 50 marasa lafiya na HCC. An sanya jigon wasu kwayoyin halittarsu guda hudu (APC, GSTP1, RASSF1A, da SFRP1) don bincikar bincike daidai, yayin da aka ruwaito methylation na RASSF1A a matsayin mai tantance halitta. Binciken na ƙarshe ya binciki ctDNA a masu amfani da HCC ta hanyar yin amfani da fasaha mai zurfi ... Sakamakon haka, an gano adadin DNA aberrant a cikin mahaɗin HBV guda biyu ba tare da tarihin HCC ba a lokacin karbar jini, amma wanda ya ci gaba da HCC a lokacin gogewa. Wannan binciken ya bude kofa don kimanta bambancin lambar ƙwaƙwalwa a ctDNA azaman kayan aiki na nunawa don ganowar HCC da wuri.
Kalma Daga
Liquid biopsies ne mai ban sha'awa sabon tsarin kula da kwayoyin halitta. A halin yanzu, wasu biopsies na ruwa, waɗanda ke bada cikakkun labarun kwayoyin, suna samuwa ga likitoci don taimakawa bayanan kwayoyin da aka samu daga kwayar halitta. Akwai kuma wasu kwayoyin halitta da za a iya amfani dashi a maimakon gurgunan halittu-lokacin da ba a samu biopsies ba.
Yana da muhimmanci a tuna cewa yawancin gwaji na biopsy yana gudana a halin yanzu kuma ana bukatar karin bincike akan jiki daga mai amfani da maganin wannan maganin.
> Sources:
> Gwajin Blood don Canjin Canjin yanayi a Tumors yana nuna alƙawari ne a matsayin madadin maganin tumo. NIH.
> Heitzer E, Ulz P, Geigl JB. Tsara kwayar cutar ta DNA a matsayin kwayar halitta na ruwa don ciwon daji. Mahimmin Kimiyya. 2015; 61: 112-123. Doi: 10.1373 / clinchem.2014.222679
> Lagbaa J, Villanueva A. Liquid biopsy a cikin ciwon hanta. Magani Binciken. 2015; 19 (105): 263-73.
> Halittar ruwa: Ta amfani da DNA a Blood don gano, Biye, da kuma magance Ciwon daji. NIH.
> Umetani N, et al. Mafi yawan adadin DNA mai rarraba a cikin kwayar cutar fiye da plasma ba ya haifar da cutar ta hanyar gurbata DNA mai raɗaɗi yayin rabuwa. Ann NY Acad Sci. 2006; 1075: 299-307.
> Wellstein A. Maganar Farko a cikin Pharmacotherapy of Cancer. A cikin: Brunton LL, Hilal-Dandan R, Knollmann BC. eds. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13th New York, NY: McGraw-Hill.