Oussama Aazzane

Objective: The objective of our study is to evaluate the predictive value of cytoplasmic Galectin-3 (Gal-3) expression in tumor cells (TCs) as well as in tumor-infiltrating immune cells (TIICs), including tumor-associated macrophages (TAM), tumor-associated neutrophils (TAN), and tumor-associated lymphocytes (TAL), in Moroccan patients with unresectable non-small cell lung cancer (NSCLC). Methods: This is a prospective study conducted between 2019 and 2023 on 56 Moroccan patients diagnosed with unresectable NSCLC. These patients were treated with platinum-based doublet chemotherapy and followed at the Mohammed VI Center for Cancer Treatment at CHU Ibn Rochd in Casablanca. Immunohistochemistry (IHC) was used to assess Gal-3 (clone 9C4) expression in TCs and TIICs (TAM, TAN, and TAL). The characteristics of the patients were obtained from the patients’ medical records. Statistical analysis, including Kaplan-Meier survival analysis and Cox regression, was performed using SPSS v.21. Results: Survival analysis across different subgroups revealed that only patients with high Gal-3 expression in TCs, along with positive expression in TIICs or TAL, exhibited significantly improved overall survival (OS = 16.81 months, p = 0.007; OS = 15.95 months, p = 0.034) compared to other subgroups. Additionally, multivariate analysis showed that poor performance status (PS 1-2) and the presence of bone metastases were significantly associated with decreased progression-free survival (PFS) (p = 0.015 and p = 0.029, respectively). The histological type (squamous cell carcinoma) was significantly correlated with OS (p = 0.000). Conclusion: The concomitant expression of Gal-3 in TCs (high expression), TIICs, and TAL may serve as a predictive biomarker for chemotherapy response in patients with unresectable NSCLC.

Colorectal cancer (CRC) is the third most diagnosed cancer and a leading cause of cancer-related mortality in Morocco, often detected at late stages. Circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers for CRC detection, with miR-21, miR-29a, and miR-92a showing significant diagnostic potential. This study aimed to evaluate the expression levels of these miRNAs in a Moroccan population and their efficacy as diagnostic biomarkers. Methods: A prospective study was conducted using blood samples from 50 CRC patients and 50 healthy controls. Circulating miRNA expression levels were quantified through reverse transcription quantitative PCR (RT-qPCR), with normalization to miR-1228-3p. Statistical analyses, including the Mann–Whitney U test, Receiver Operating Characteristic (ROC) curve analysis, sensitivity (Sen), and specificity (Spe) evaluations, were performed to assess the diagnostic accuracy of individual miRNAs and their combined performance as panels. Results: The expression levels of miR-21, miR-29a, and miR-92a were significantly elevated in CRC patients compared to healthy controls (all p < 0.001). ROC analysis demonstrated that miR-92a exhibited the highest individual diagnostic performance (AUC: 0.938), followed by miR-21 (AUC: 0.907) and miR-29a (AUC: 0.898). Sensitivity and specificity were 88% and 90%, 92% and 56%, and 76% and 94%, respectively. Combinatorial analysis revealed that the miR-29a and miR-92a panel achieved the highest diagnostic accuracy (AUC: 0.976), surpassing individual miRNAs and other combinations, highlighting its potential as a robust, non-invasive biomarker panel for CRC. Conclusions: This study highlights the potential of the miR-29a and miR-92a combination, which achieved excellent diagnostic efficiency (AUC: 0.976). These findings underscore miRNA utility in enhancing early detection and reducing CRC-related mortality in Morocco.

Inroduction: The question of whether tumor expression of PD-L1 and the presence of distant metastasis could influence the efficacy of immunotherapy represents a major challenge and needs to be further elucidated. The aim of this study is to evaluate the predictive significance of tumor expression of PD-L1 as well as the number and site of metastasis in non-small cell lung cancer (NSCLC) among Moroccan patients treated with immunotherapy.Material and Methods: Between January 2019 and February 2023, we recruited Moroccan patients with metastatic NSCLC. All were treated with immunotherapy, either as monotherapy or in combination with chemotherapy. Immunohistochemistry was used to assess PD-L1 (clone 22C3) and ALK (clone D5F3) status. EGFR status was established by qPCR. Tumor PD-L1 expression was classified into 2 levels: TPS <1% (negative expression) and TPS ≥1% (positive expression). Statistical analysis was performed using SPSS Statistics V.21 software. Results: The median age of patients (N=40) was 67 years (39- 92 years) and the sex ratio was 9. Disease dissemination revealed that 22.5% (N=9) of patients had a metastatic burden ≥ 3 (MB≥3). As for the sites of metastasis, the results showed that 20% (N=8), 10% (N=4), 42.5% (N=17), 22.5% (N=9), 27.5% (N=11), 45% (N=18) and 27.5% (N=11) of patients had developed lymph node, liver, bone, brain, pleural, contralateral lung and adrenal metastasis respectively. Positive PD-L1 expression was significantly associated with shorter overall survival (OS = 17.19 vs. 28.85 months, p=0.01). High metastatic burden (MB ≥ 3) was associated with lower objective response rate (ORR), shorter progression-free survival (PFS), and reduced OS, respectively (ORR = 0 vs. 58.06%, p=0.002; PFS = 10.23 vs. 25.27 months, p=0.001; and OS = 11.60 vs. 27.91 months, p=0.003). Only the presence of osseous metastasis was significantly associated with lower ORR, shorter PFS, and OS compared to other metastatic locations (ORR = 5.88 vs. 73.9%, p=0.000; PFS = 10.72 vs. 31.33 months, p=0.000; and OS = 11.39 vs. 36.17 months, p=0.000). Finally, the presence of hepatic metastasis was significantly associated with shorter PFS (10.75 months) compared to those without hepatic metastasis (22.53 months) (p=0.046). Finally, the results of the multivariate analysis revealed that the presence of bone metastasis was strongly correlated with a significant decrease in progression-free survival (p=0.001) as well as overall survival (p=0.002). Conclusion: Our results suggest that tumor expression of PD-L1 and metastatic burden should play a significant role in predicting the response to immunotherapy. Furthermore, it is important to note that the presence of osseous and hepatic metastasis could negatively influence the clinical outcomes of immunotherapy.

Psoriasis still has an unknown etiology. Genetic predisposition shows the association between HLA-Cw6 allele and psoriasis. Although biotherapies have been proven effective in psoriasis treatment, methotrexate (MTX) is still used as a first-line systemic therapy due to its efficacy/affordability, but the differential response to MTX is mostly related to interindividual genetic variability and remains an issue. Our study aimed to analyze HLA-C allele frequencies in a sample of Moroccan psoriatic patients and assess the therapeutic response to MTX. Whole blood of 54 Moroccan psoriatic patients was collected and DNA was extracted. Patients’ HLA-C locus was genotyped by PCR-SSO. Results were analyzed with Luminex xMAP Technology and Match-it DNA Evolution 3.4. HLA-C typing results of 77 sex- and age-matched unrelated non-psoriatic healthy subjects were included. We observed no difference in the allelic distribution of HLA-C between patients and healthy controls, suggesting that none of the HLA-C alleles were significantly associated with psoriasis. Moreover, the HLA-C*07 allele was associated with a late age at disease onset (>30 years old) (p = 0.007). No statistically significant association was found between HLA-C allele expression and response to MTX, despite a higher frequency of HLA-C*06 in responders compared to non-responders. Thus, HLA-C*07 could be a biomarker of late psoriasis onset in the Moroccan population.