Construction and Clinical Translation of Causal Pan-Cancer Gene Score Across Cancer Types

Abstract

Pan-cancer strategy, an integrative analysis of different cancer types, can be used to explain oncogenesis and identify biomarkers using a larger statistical power and robustness. Fine-mapping defines the casual loci, whereas genome-wide association studies (GWASs) typically identify thousands of cancer-related loci and not necessarily have a fine-mapping component. In this study, we develop a novel strategy to identify the causal loci using a pan-cancer and fine-mapping assumption, constructing the CAusal Pan-cancER gene (CAPER) score and validating its performance using internal and external validation on 1,287 individuals and 985 cell lines. Summary statistics of 15 cancer types were used to define 54 causal loci in 15 potential genes. Using the Cancer Genome Atlas (TCGA) training set, we constructed the CAPER score and divided cancer patients into two groups. Using the three validation sets, we found that 19 cancer-related variables were statistically significant between the two CAPER score groups and that 81 drugs had significantly different drug sensitivity between the two CAPER score groups. We hope that our strategies for selecting causal genes and for constructing CAPER score would provide valuable clues for guiding the management of different types of cancers.

A pan-cancer analysis of copper homeostasis-related gene lipoyltransferase 1: Its potential biological functions and prognosis values

“…Cancers are global health problems, affecting human health and quality of life. According to the statistics from World Health Organization, cancers are the main endangering cause of human life ( Tao et al, 2021 ; Yu and Mitrofanova, 2021 ). Identifying the valuable pan-cancer genes would be crucial to clarify the underlying mechanisms for occurrence and development of different tumors ( He et al, 2021 ; Shi et al, 2021 ).…”

Pan-cancer analysis of HS6ST2: associations with prognosis, tumor immunity, and drug resistance

“…Cancer stands as a prominent contributor to human mortality, exerting substantial adverse effects on both global societal well-being and economic aspects [1,2]. Cancer arises from genetic alterations in the key genes which lead to uncontrolled cell growth [3][4][5][6][7].…”

A pan-cancer analysis of the role of USP5 in human cancers

“…Cancer is a leading cause of human death, with significant negative impacts on social health and the economy all over the world 1 , 2 . Although the development of surgery, chemoradiotherapy, targeted therapy, and immunotherapy have improved the therapeutic effect on cancer, the prognosis and survival rate of cancer patients still remains poor for many reasons, including drug resistance and side effects 3 .…”