Laryngeal squamous cell carcinoma (LSCC) poses significant clinical challenges due to pronounced tumor heterogeneity. To identify robust, consistent biomarkers across cohorts, we integrated bulk RNA sequencing (RNA-seq) data from GSE127165 and GSE142083 and validated candidate biomarkers in the external cohort GSE13060. Candidate gene prioritization incorporated differentially expressed genes, weighted gene co-expression network analysis (WGCNA) results, and markers of malignant epithelial cells exhibiting high copy number variation (High-CNV) derived from single-cell RNA sequencing (scRNA-seq) (GSE206332). Additional analyses included functional enrichment, immune association (adjusted for tumor purity), quasi-temporal analysis, and CellChat inference to elucidate the biological roles of top genes. The integrated approach identified 254 differentially expressed genes (DEGs), comprising 86 upregulated and 168 downregulated genes. WGCNA revealed a tumor-associated module containing 870 genes. Intersecting these findings with high-CNV malignant epithelial markers reduced the candidate pool to 16 genes, and LASSO regression retained five key features: MYBL2, KRT17, UCHL1, PTHLH, and ODC1. Among these, MYBL2 demonstrated the strongest and most consistent performance. MYBL2 was further associated with proliferative programs, including E2F targets, the G2/M checkpoint, DNA repair, and MYC targets. Gene signatures from these subclusters were enriched in bulk tumors and positively correlated with MYBL2 expression in independent cohorts. The results also indicate that MYBL2-high malignant epithelial states are linked to distinct connectivity patterns within the tumor microenvironment.
The use of cell therapy for clinical applications has seen a dramatic increase in recent years, primarily in oncology, especially with the use of chimeric antigen receptor (CAR) T-cell therapies. However, there are some barriers to the widespread adoption of CAR-T cell therapies globally, primarily because of the high cost of manufacturing these cells and clinical infrastructure considerations. We reviewed the different strategies adopted across Asia to implement CAR-T cell therapy and found that these included patient assistance programs, close engagement with funders, cost-effectiveness studies, on-site manufacturing of CAR-T cells, and joint ventures between local partners and foreign pharmaceutical companies. Although on-site manufacturing can reduce the cost of genetic engineering and expansion, it does not address many other hidden costs and quality considerations. Future growth in large-scale regional manufacturing, facilitated by cutting-edge science and innovation, could reduce costs through economies of scale and facilitate the eagerly needed global access.
The number of hematopoietic stem cell transplantations (HCTs) is increasing annually worldwide, and the Asia-Pacific (AP) region is no exception. We report on the absolute number of HCTs in 2018 and 2019 and the trends in graft selection and disease indication in the past few decades. In 2018, 24,292 HCTs were performed in the AP region, of which 8,754 (36.0%) were autologous and 15,538 (64.0%) were allogeneic. Among the allogeneic HCTs, 10,552 (67.9%) of the recipients were related to their donors, whereas 4,986 (32.1%) were unrelated. In 2019, 27,583 HCTs were reported, of which 17,613 (63.9%) were allogeneic and 9,970 (36.1%) were autologous. Although, in 2010, there was a nearly equal number of related and unrelated HCTs, the difference has shown an annual increase, with more than double (2.05) the number of related than unrelated HCTs in 2019. Recent trends in the AP region show that peripheral blood has overwhelmingly surpassed the bone marrow as a graft source for both related and unrelated HCTs, with the haploidentical donor type being preferred; however, their trends in each country/region were quite different among countries/regions. In 2019, the main conditions requiring HCT were acute myelogenous leukemia (n=6,629 [24.0%]), plasma cell disorders (PCD) (n=4,935 [17.9%]), malignant lymphoma (ML) (n=4,106 [14.9%]), acute lymphoblastic leukemia (AML) (n=3,777 [13.7%]), myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm (n=1,913 [6.9%]), severe aplastic anemia (n=1,671 [6.1%]), and hemoglobinopathy (n=910 [3.3%]). PCD and ML were the main indications for autologous HCT, and the number of PCD cases has grown more prominent than the corresponding of ML. The increased number of allogeneic transplants for hemoglobinopathy remains prominent, as well as that of AML and acute lymphocytic leukemia for the past 5 years. There was a significant regional variation in the number of facilities performing HCTs, ranging from one in Mongolia and Nepal to 313 in Japan, and differing regional densities varying from 0.1 in Indonesia and Pakistan to 24.7 in Japan. The total transplant density per 10 million population in each country/region also differed (0.2 in Indonesia and 627 in New Zealand). This annual Activity Survey aims to help all participating countries/regions understand the changes in HCT, serve as an asset in promoting HCT activities in the AP region, and be used as a reference for comparison with other registries from Europe and the United States.
The Asia-Pacific Blood and Marrow Transplantation Group (APBMT) has been conducting annual surveys on the activity of hematopoietic stem cell transplants since 2007. The APBMT Data Center collected the following data in 2017. A total of 21,504 transplants were registered from 733 transplant centers of 20 countries/regions in the Asia-Pacific (AP) region. Five countries/regions comprised 89.4% of all transplants - China (6,979), Japan (5,794), South Korea (2,626), India (2,034), and Australia (1,789). The number of centers in these five countries/regions also comprised 88.9% of all centers: Japan (373), China (123), India (66), Australia (45), and South Korea (44). The overall ratio between autologous and allogeneic transplants was 37.0% and 63.0%, respectively, but the ratios varied significantly among countries/regions. Autologous transplants have surpassed allogeneic transplants in Thailand, Australia, Vietnam, New Zealand, Singapore, and Iran. In contrast, the proportion of allogeneic transplants comprised over 70% of all transplants in Pakistan, China, and Hong Kong. These ratios were compared by the Data Center among countries/regions that performed more than 50 transplants. The proportion of related and unrelated transplants also differed among countries/regions. The number of unrelated transplants was more than related ones in Japan (2,551 vs. 1,202) and Australia (329 vs. 291), whereas more than 80% of all transplants were related transplants in Malaysia (90.9%), India (89.5%), Iran (87.2%), Vietnam (85.7%), China (80.9%), and Thailand (80.6%). All transplant activities were related transplants in Pakistan, the Philippines, Myanmar, and Nepal, and no allogeneic transplants were performed in Bangladesh and Mongolia. Regarding the indications for transplants, acute myeloid leukemia (AML) was the most common disease for allogeneic transplant (4,759, 35.1% of allogeneic transplants), while plasma cell disorder (PCD) was the most common disease for autologous transplant (3,701, 27.3% of all autologous transplants). Furthermore, the number of transplants for hemoglobinopathy has steeply increased in this region compared with the rest of disease indications (677, 3.1% of all transplants). APBMT covers a broad area globally, including countries/regions with diverse disease distribution, development of HSCT programs, population, and economic power. Consistent and continuous activity surveys considering those elements in each country/region revealed the HSCT field's diverse characteristics and background factors in this region.
COVID-19 became a global pandemic in 2020 and significantly affected the activity of hematopoietic cell transplants (HCT) worldwide. Despite these challenges, a total of 28,793 transplants, including 18,518 allogeneic and 10,275 autologous transplants, were performed in 719 facilities in 2020 in the Asia-Pacific (AP) region. This represented a 5.1% increase in allogeneic transplants and a 3.1% increase in autologous transplants, an overall increase of 4.4% compared to the numbers in 2019. With respect to the donor source, haploidentical transplants increased significantly by 18.6%, related transplants by 8.8%, and cord blood transplants (CBT) by 9.2%. However, the number of unrelated transplants, excluding CBT, decreased for the first time by 8.2%. As a result, COVID-19 facilitated the growth of haploidentical transplants due to cross-border restrictions. Regarding the changes in the total number of transplants by country/region in 2020, it increased by 2,048 transplants in China, followed by Japan (210 transplants) and Korea (230 transplants); however, 14 of the 22 countries and regions decreased their number of transplants in 2020 compared to the previous year. There was no correlation between the increase or decrease in the number of transplants in 2020 and the Gross National Income (GNI) per capita of each country/region in 2020, as well as Domestic General Government Health Expenditure as a percentage of General Government Expenditure (GGHE-D/GGE). In 2021, the total number of transplants in this region was 34,754. With the exception of a few countries/regions that decreased the number of transplants in 2020, most countries/regions have started to see a recovery in 2021. The COVID-19 pandemic significantly affected the supply chain and logistics involved in HCT rather than its numbers; however, we have found ways to overcome logistical challenges to carry out transplant medicine without delay, even under these circumstances.