TY - JOUR
T1 - Dissecting molecular, pathological, and clinical features associated with tumor neural/neuroendocrine heterogeneity
AU - Cai, Ling
AU - DeBerardinis, Ralph J.
AU - Xiao, Guanghua
AU - Minna, John D.
AU - Xie, Yang
N1 - Funding Information:
This study is supported by funding from the American Cancer Society (IRG-21-142-16 to L.C.), the National Institutes of Health (R01GM140012, R01GM141519, R01DE030656, U01CA249245 to G.X. U01AI156189, P30CA142543, R35GM136375 to Y.X. P50CA70907, U01CA213338, U24CA213274 to J.D.M. R35CA220449 to R.J.D.), the Cancer Prevention and Research Institute of Texas (RP190107 to G.X. RP180805 to Y.X.), and the Howard Hughes Medical Institute to R.J.D. The results from this paper are in part based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga. This article is subject to HHMI's Open Access to Publications policy. HHMI lab heads have previously granted a nonexclusive CC BY 4.0 license to the public and a sublicensable license to HHMI in their research articles. Pursuant to those licenses, the author-accepted manuscript of this article can be made freely available under a CC BY4.0 license immediately upon publication. L.C. conceptualized the study, designed the methodology, curated the data, and performed formal analyses. Y.X. J.D.M. G.X. and R.J.D. provided funding, supervision, and critical inputs for the study. L.C. drafted the original manuscript. R.J.D. reviewed and edited the article. All authors have read and approved the final version of this manuscript. R.J.D. is an advisor for Agios Pharmaceuticals and Vida Ventures and a co-founder of Atavistik Bio. J.D.M. receives licensing fees from the NIH and UTSW for distribution of human tumor cell lines.
Funding Information:
This study is supported by funding from the American Cancer Society ( IRG-21-142-16 to L.C.), the National Institutes of Health ( R01GM140012 , R01GM141519 , R01DE030656 , U01CA249245 to G.X., U01AI156189 , P30CA142543 , R35GM136375 to Y.X., P50CA70907 , U01CA213338 , U24CA213274 to J.D.M., R35CA220449 to R.J.D.), the Cancer Prevention and Research Institute of Texas ( RP190107 to G.X. RP180805 to Y.X.), and the Howard Hughes Medical Institute to R.J.D.
Publisher Copyright:
© 2023 The Author(s)
PY - 2023/6/16
Y1 - 2023/6/16
N2 - Lineage plasticity, especially transdifferentiation between neural/neuroendocrine (NE) and non-NE lineage, has been observed in multiple cancer types and linked to increased tumor aggressiveness. However, existing NE/non-NE subtype classifications in various cancer types were established through ad hoc approaches in different studies, making it difficult to align findings across cancer types and extend investigations to new datasets. To address this issue, we developed a generalized strategy to generate quantitative NE scores and a web application to facilitate its implementation. We applied this method to nine datasets covering seven cancer types, including two neural cancers, two neuroendocrine cancers, and three non-NE cancers. Our analysis revealed significant NE inter-tumoral heterogeneity and identified strong associations between NE scores and molecular, histological, and clinical features, including prognosis in different cancer types. These results support the translational utility of NE scores. Overall, our work demonstrated a broadly applicable strategy for determining the NE properties of tumors.
AB - Lineage plasticity, especially transdifferentiation between neural/neuroendocrine (NE) and non-NE lineage, has been observed in multiple cancer types and linked to increased tumor aggressiveness. However, existing NE/non-NE subtype classifications in various cancer types were established through ad hoc approaches in different studies, making it difficult to align findings across cancer types and extend investigations to new datasets. To address this issue, we developed a generalized strategy to generate quantitative NE scores and a web application to facilitate its implementation. We applied this method to nine datasets covering seven cancer types, including two neural cancers, two neuroendocrine cancers, and three non-NE cancers. Our analysis revealed significant NE inter-tumoral heterogeneity and identified strong associations between NE scores and molecular, histological, and clinical features, including prognosis in different cancer types. These results support the translational utility of NE scores. Overall, our work demonstrated a broadly applicable strategy for determining the NE properties of tumors.
KW - Cancer
KW - Cancer systems biology
KW - Computational bioinformatics
UR - http://www.scopus.com/inward/record.url?scp=85161512775&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85161512775&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2023.106983
DO - 10.1016/j.isci.2023.106983
M3 - Article
C2 - 37378310
AN - SCOPUS:85161512775
SN - 2589-0042
VL - 26
JO - iScience
JF - iScience
IS - 6
M1 - 106983
ER -