Prognostic model development and molecular subtypes identification in bladder urothelial cancer

29 Feb 2024
Prognostic model development and molecular subtypes identification in bladder urothelial cancer

A new research paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 3, entitled, “Prognostic model development and molecular subtypes identification in bladder urothelial cancer by oxidative stress signatures.”

Mounting studies indicate that oxidative stress (OS) significantly contributes to tumour progression. In this new study, researchers Ying Dong, Xiaoqing Wu, Chaojie Xu, Yasir Hameed, Mostafa A. Abdel-Maksoud, Taghreed N. Almanaa, Mohamed H. Kotob, Wahidah H. Al-Qahtani, Ayman M. Mahmoud, William C. Cho, and Chen Li from Shenzhen Second People’s Hospital, China Academy of Chinese Medical Sciences, Peking University, The Islamia University of Bahawalpur, King Saud University, University of Vienna, Manchester Metropolitan University, Queen Elizabeth Hospital, and Free University of Berlin focused on bladder urothelial cancer (BLCA), an escalating malignancy worldwide that is growing rapidly. 

“Our objective was to verify the predictive precision of genes associated with overall survival (OS) by constructing a model that forecasts outcomes for bladder cancer and evaluates the prognostic importance of these genetic markers.”

Transcriptomic data were obtained from TCGA-BLCA and GSE31684, which are components of the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively.

To delineate distinct molecular subtypes, the researchers employed the non-negative matrix factorisation (NMF)method.

The significance of OS-associated genes in predicting outcomes was assessed using lasso regression, multivariate Cox analysis, and univariate Cox regression analysis.

For external validation, they employed the GSE31684 dataset.

CIBERSORT was utilised to examine the tumour immune microenvironment (TIME).

A nomogram was created and verified using calibration and receiver operating characteristic (ROC) curves, which are based on risk signatures.

The team examined variations in clinical characteristics and tumour mutational burden (TMB) among groups classified as high-risk and low-risk. To evaluate the potential of immunotherapy, the immune phenomenon score (IPS) was computed based on the risk score.

In the end, the pRRophetic algorithm was employed to forecast the IC50 values of chemotherapy medications.

“In our research, we examined the expression of 275 genes associated with OS in 19 healthy and 414 cancerous tissues of the bladder obtained from the TCGA database.”

As a result, a new risk signature was created that includes 4 genes associated with OS (RBPMS, CRYAB, P4HB, and PDGFRA).

The researchers found two separate groups, C1 and C2, that showed notable variations in immune cells and stromal score.

According to the Kaplan-Meier analysis, patients classified as high-risk experienced a considerably reduced overall survival in comparison to those categorised as low-risk (P<0.001).

The predictive capability of the model was indicated by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve surpassing 0.6.

Their model showed consistent distribution of samples from both the GEO database and TCGA data.

Both the univariate and multivariate Cox regression analyses validated the importance of the risk score in relation to overall survival (P < 0.001).

According to their research, patients with a lower risk profile may experience greater advantages from using a CTLA4 inhibitor, whereas patients with a higher risk profile demonstrated a higher level of responsiveness to Paclitaxel and Cisplatin.

In addition, methotrexate exhibited a more positive outcome in patients with low risk compared to those with high risk.

“Our research introduces a novel model associated with OS gene signature in bladder cancer, which uncovers unique survival results. This model can assist in tailoring personalised treatment approaches and enhancing patient therapeutic effect in the management of bladder cancer.”

Source: Impact Journals LLC