Pan-Cancer Characterization of Intratumoral Autonomic Innervation in 32 Cancer Types in the Cancer Genome Atlas

Abstract

Over the past two decades, multiple studies have demonstrated the important role that the autonomic nervous system (ANS) plays in tumorigenesis and cancer progression. However, the mechanisms by which this process occurs have only recently begun to be elucidated. Further, the extent of autonomic innervation in various cancer types and its effects on tumor molecular, immunological, and histopathological features, as well as on patient outcomes, are not yet fully characterized. In this study, we analyzed intratumoral ANS gene expression signatures, including overall intratumoral neuron growth and sympathetic and parasympathetic markers, across 32 cancer types using tumor transcriptomic and clinical annotation data available from The Cancer Genome Atlas (TCGA). Our analysis revealed wide variations in intratumoral ANS expression both within and across cancer types. The association of ANS signatures with tumor histopathological characteristics and survival outcomes also varied by cancer type. We found intratumoral ANS expression to be commonly correlated with angiogenesis, TGF-β signaling, and immunosuppression in the tumor microenvironment of many cancer types, which provide mechanistic insights into the involvement of intratumoral innervation in cancer development and progression. Our findings suggest that the potential benefits of cancer therapies targeting β-adrenergic receptor-mediated stress signaling pathways are likely dependent on cancer type.

Effects of fear of cancer recurrence on subjective physical and mental health in breast cancer patients: The intermediary role of heart rate variability

“…After controlling for age, BMI, KPS and tumor stage, low HF‐HRV predicted poor HRQoL in BC patients. Recently, it has been found that ANS in tumors is usually associated with angiogenesis and immunosuppression in the tumor microenvironment, thus participating in the development and progression of cancer 40 . An animal experiment showed that there are nerve fibers embedded in BC masses, and the ANS has a direct influence on tumor growth and metastasis.…”

The role of dynamic interplay exists between sympathetic and parasympathetic nerve in gastric tumorigenesis

“…Autonomic nervous system (ANS) signatures are validated using marker genes 19 . Differentially expressed genes (DEGs) among GPL subtypes are determined using the “limma” R package with FC >1.4 and FDR <0.05.…”

“…-3 of 16 2.3 | Nerves signatures, pathways and immune microenvironment assessment Autonomic nervous system (ANS) signatures are validated using marker genes. 19 Differentially expressed genes (DEGs) among GPL subtypes are determined using the "limma" R package with FC >1.4 and FDR <0.05. GC driver genes (Table S2) and nerve-cancer related genes (Table S3) were used to obtain differentially expressed driver-related and nerve-regulated genes.…”

Dedifferentiated Schwann cells promote perineural invasion mediated by the PACAP paracrine signalling in cervical cancer

“…Mounting evidence has indicated that the nervous system plays an essential role in cancer progression. Tumour cells release various neurotrophic factors to promote their own innervation 1–3 . In turn, infiltrating nerves also mediate various malignant biological processes of the tumour 4 .…”

“…Tumour cells release various neurotrophic factors to promote their own innervation. [1][2][3] In turn, infiltrating nerves also mediate various malignant biological processes of the tumour. 4 Such discoveries make identification of predictive markers and mechanisms of cancer neuroscience an area of emerging research.Most reports about the interactions between solid tumours and the nervous system have described perineural invasion (PNI).…”