Transcriptomic Mapping of Non-Small Cell Lung Cancer K-RAS p.G12C Mutated Tumors: Identification of Surfaceome Targets and Immunologic Correlates

Abstract

Targeting K-RAS-mutant non-small cell lung cancer (NSCLC) with novel inhibitors has shown promising results with the recent approval of sotorasib in this indication. However, progression to this agent is expected, as it has previously been observed with other inhibitors. Recently, new immune therapeutics, including vectorized compounds with antibodies or modulators of the host immune response, have demonstrated clinical activity. By interrogating massive datasets, including TCGA, we identified genes that code for surface membrane proteins that are selectively expressed in K-RAS mutated NSCLC and that could be used to vectorize novel therapies. Two genes, CLDN10 and TMPRSS6, were selected for their clear differentiation. In addition, we discovered immunologic correlates of outcome that were clearly de-regulated in this particular tumor type and we matched them with immune cell populations. In conclusion, our article describes membrane proteins and immunologic correlates that could be used to better select and optimize current therapies.

Genes whose expressions in the primary lung squamous cell carcinoma are able to accurately predict the progression of metastasis through lymphatic system, inferred from a bioinformatics analyses

“…SLC46A2 belongs to the solute carrier proteins (SLC) superfamily, which includes more than 400 transport proteins in 65 families and transport a wide variety of substances across the cell membrane and they also transport drugs across the lipid bilayer, so they play a role in carcinogenesis 29 . Consistent with our study, previously published article also described SLC46A2 as a prognostic biomarker for lung squamous cell carcinomas and lung adenocarcinomas patients 30 . Interestingly, our results showed that the SLC46A2 gene was significantly associated with metastasis and survival, indicating the importance of this gene in LUSC.…”

WITHDRAWN: Upregulated HMGB3 resulting in the poor prognosis of lung adenocarcinoma by activating stromal angiogenesis through immune microenvironment

“…While how to nd out tumor cells from human body? A biomarker with enhanced speci city and sensitivity is particularly essential [13][14][15]. The tumor biomarker is a biological molecular directly produced by tumor cells or indirectly induced by non-tumor cells.…”

Modulation of Lymphocyte Functions in the Microenvironment by Tumor Oncogenic Pathways

“…Furthermore, in different models of K-RAS activation including CRC, oncogenic K-RAS represses the expression of interferon-regulatory factor (IRF)2, which directly affects CXCL3 expression thereby promoting the influx of MDSC into the TME ( 69 , 70 ). A global downregulation of immune cells was detected in lung adenocarcinoma patients harboring mutations in the K-RAS G12C gene, which correlates with the presence of downregulated transcripts ( 71 ).…”