Identification of prognostic genes in lung adenocarcinoma immune microenvironment

Han, Lu; Huai, Qilin; Wei, Guo; Song, Peng; Kong, Demiao; Gao, Shugeng

doi:10.1097/cm9.0000000000001367

Cited by 2 publications

(1 citation statement)

References 10 publications

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“…Our investigation identified PKHD1L1 as the most frequently mutated Tdark gene across 28 types of cancer, indicating its potential as a broad therapeutic target. Notably, previous research [71][72][73][74][75][76] has also indicated the substantial involvement of PKHD1L1 in cancer, underscoring its probable significance in the development and progression of this disease. We also reported differences in the mean gene dependency scores among Tclin, Tchem, Tbio, and Tdark genes, suggesting that Tdark genes are also essential for the survival of the cancer cell lines and may be promising therapeutic targets 29,32,77 .…”

Section: Discussionmentioning

confidence: 92%

Shedding Light on the Dark Genome: Insights into the Genetic, CRISPR-based, and Pharmacological Dependencies of Human Cancers and Disease Aggressiveness

Kafita,

Nkhoma,

Dzobo

et al. 2023

Preprint

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Investigating the human genome is vital for identifying risk factors and devising effective therapies to combat genetic disorders and cancer. Despite the extensive knowledge of the "light genome", the poorly understood "dark genome" remains understudied. In this study, we integrated data from 20,412 protein-coding genes in Pharos and 8,395 patient-derived tumours from The Cancer Genome Atlas (TCGA) to examine the genetic and pharmacological dependencies in human cancers and their treatment implications. We discovered that dark genes exhibited high mutation rates in certain cancers, similar to light genes. By combining the drug response profiles of cancer cells with cell fitness post-CRISPR-mediated gene knockout, we identified the crucial vulnerabilities associated with both dark and light genes. Our analysis also revealed that tumours harbouring dark gene mutations displayed worse overall and disease-free survival rates than those without such mutations. Furthermore, dark gene expression levels significantly influenced patient survival outcomes. Our findings demonstrated a similar distribution of genetic and pharmacological dependencies across the light and dark genomes, suggesting that targeting the dark genome holds promise for cancer treatment. This study underscores the need for ongoing research on the dark genome to better comprehend the underlying mechanisms of cancer and develop more effective therapies.

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