Patient stratification based on urea cycle metabolism for exploration of combination immunotherapy in colon cancer.
Patient stratification based on urea cycle metabolism for exploration of combination immunotherapy in colon cancer.
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基于尿素循环代谢的患者分层探索结肠癌联合免疫治疗
DOI：
10.1186/s12885-022-09958-7
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发表时间：
2022-08-13
期刊：
影响因子：
3.8
通讯作者：
中科院分区：
文献类型：
--
作者：
Owing to the low ratio of patients benefitting from immunotherapy, patient stratification becomes necessary. An accurate patient stratification contributes to therapy for different tumor types. Therefore, this study aimed to subdivide colon cancer patients for improved combination immunotherapy. We characterized the patients based on urea cycle metabolism, performed a consensus clustering analysis and constructed a risk model in the cancer genome atlas cohort. Colon cancer patients were further categorized into two tags: clusters, and risk groups, for the exploration of combination immunotherapy. In addition to external validation in the Gene Expression Omnibus datasets, several images of immunohistochemistry were used for further validation. Patient characterization based on urea cycle metabolism was related to immune infiltration. An analysis of consensus clustering and immune infiltration generated a cluster distribution and identified patients in cluster 1 with high immune infiltration levels as hot tumors for immunotherapy. A risk model of seven genes was constructed to subdivide the patients into low- and high-risk groups. Validation was performed using a cohort of 731 colon cancer patients. Patients in cluster 1 had a higher immunophenoscore (IPS) in immune checkpoint inhibitor therapy, and those other risk groups displayed varying sensitivities to potential combination immunotherapeutic agents. Finally, we subdivided the colon cancer patients into four groups to explore combination immunotherapy. Immunohistochemistry analysis showed that protein expression of two genes were upregulated while that of other two genes were downregulated or undetected in cancerous colon tissues. Using subdivision to combine chemotherapy with immunotherapy would not only change the dilemma of immunotherapy in not hot tumors, but also promote the proposition of more rational personalized therapy strategies in future. The online version contains supplementary material available at 10.1186/s12885-022-09958-7.
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影响因子：
5.2
作者：
Meessen S;Currey N;Jahan Z;Parker HW;Jenkins MA;Buchanan DD;Hopper JL;Segelov E;Dahlstrom JE;Kohonen-Corish MRJ
通讯作者：
Kohonen-Corish MRJ
影响因子：
29
作者：
Pavlova NN;Thompson CB
通讯作者：
Thompson CB
DOI：
10.1093/database/baq020
发表时间：
2010-08-05
期刊：
Database : the journal of biological databases and curation
影响因子：
--
作者：
Safran M;Dalah I;Alexander J;Rosen N;Iny Stein T;Shmoish M;Nativ N;Bahir I;Doniger T;Krug H;Sirota-Madi A;Olender T;Golan Y;Stelzer G;Harel A;Lancet D
通讯作者：
Lancet D
DOI：
10.1016/s0140-6736(17)33326-3
发表时间：
2018-03-17
期刊：
Lancet (London, England)
影响因子：
--
作者：
Allemani C;Matsuda T;Di Carlo V;Harewood R;Matz M;Nikšić M;Bonaventure A;Valkov M;Johnson CJ;Estève J;Ogunbiyi OJ;Azevedo E Silva G;Chen WQ;Eser S;Engholm G;Stiller CA;Monnereau A;Woods RR;Visser O;Lim GH;Aitken J;Weir HK;Coleman MP;CONCORD Working Group
通讯作者：
CONCORD Working Group
影响因子：
6
作者：
Stupnikov A;McInerney CE;Savage KI;McIntosh SA;Emmert-Streib F;Kennedy R;Salto-Tellez M;Prise KM;McArt DG
通讯作者：
McArt DG