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Soluble Mesothelin-Related Peptide as a Prognosticator in Pleural Mesothelioma Patients Receiving Checkpoint Immunotherapy

ABSTRACT: Objective: Immune checkpoint therapy (ICT) has significantly impacted malignant pleural mesothelioma (MPM) treatment. Despite some promising results from combination therapies, nearly half of MPM patients do not benefit, underscoring the urgent need for reliable predictive biomarkers. This study assesses the prognostic value of serum soluble mesothelin-related peptide (SMRP) and PD-L1 levels in MPM patients receiving ICT. Results: Seventy-seven patients (62%) were treated with either anti-PD-(L)1 monotherapy, while the remaining 38% were given combination ICT. Higher pre-ICT SMRP levels were notably observed in epithelioid versus non-epithelioid MPM. Serum PD-L1 levels did not show significant differences between the groups. Univariable analysis identified durable clinical benefits, development of immune-related adverse events, and SMRP levels as significantly associated with OS. Multivariable analysis confirmed SMRP as an independent prognostic factor, with lower levels (≤1.35 nmol/L) correlating with improved OS (median survival: 23 months vs. 13 months). This finding was further validated in the prospective ICT clinical trial cohort. Conclusions: SMRP emerges as a promising serum biomarker for predicting survival in MPM patients treated with ICT, warranting further prospective investigation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE274983 | GEO | 2024/08/19

REPOSITORIES: GEO

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Project description:Purpose: To find out the patients who are most sensitive and effective to the anti-PD-L1 and TGF-β bifunctional fusion protein in the treatment of recurrent cervical cancer. Patients and methods: We report two cases of recurrent cervical cancer treated with the anti-PD-L1 and TGF-β bifunctional fusion protein. We described the clinical course, clinical characteristics, and genetic characteristics of the two patients, and analyzed the changes of gene expression in the two patients after treatment. Results: Although PD-L1 expression and HPV status were same in the two patients, the treatment effect of two patients with recurrent cervical cancer was different, according to the evaluation of enhanced computed tomography (CT), one was partial response (PR) and the other was progressive disease (PD), which may indicate that PD-L1 expression and HPV status of patients is not enough to predict the effectiveness of the anti-PD-L1 and TGF-β bifunctional fusion protein treatments. Then, we demonstrated that the changes of peripheral blood lymphocytes of two patients during the treatment had different trends. Moreover, number of alterable genes in PR patient is much greater than that in PD patient, indicating PR patient may be more sensible to the anti-PD-L1 and TGF-β bifunctional fusion protein treatments. Total 4844 genes changing-fate gene set selected which is believed conducting anti-cancer function during the anti-PD-L1 and TGF-β bifunctional fusion protein treatments. Furthermore, we identified that changing-fate genes were correlated with female reproductive organ cancer, infectious disease, inflammatory disease, immune system, indicating these genes may conducting anti-cancer, anti-inflammation and immune function. Conclusion: Anti-PD-L1 and TGF-β bifunctional fusion protein is feasible for the treatment of recurrent cervical cancer. Multi-center, large-sample prospective clinical studies are still needed to further explore the efficacy of anti-PD-L1 and TGF-β bifunctional fusion protein in recurrent cervical cancer and screen appropriate patients, so as to achieve the maximum survival benefit of patients.

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Soluble Mesothelin-Related Peptide as a Prognosticator in Pleural Mesothelioma Patients Receiving Checkpoint Immunotherapy

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