Background: Transglutaminase 2 (TG2), a member of the transglutaminase family, also known as tissue transglutaminase, plays a fundamental role in cancer growth and progression. In this study, we aimed to comprehensively review the evidence of TG2 as a prognostic biomarker in solid tumors. Methods: PubMed, Embase, and Cochrane databases were searched for human studies with clearly described cancer types if they presented the relationship between TG2 expression and prognostic indicators from inception to February 2022. Two authors independently screened the eligible studies and extracted the relevant data. The association between TG2 and overall survival (OS), disease-free survival (DFS), and relapse-free survival (RFS) was described as hazard ratio (HR) and their corresponding 95% confidence intervals (CIs). Statistical heterogeneity was assessed using Cochrane Q-test and Higgins I-squared statistic. A sensitivity analysis was conducted by sequentially omitting the impact of each study. Publication bias was assessed by Egger's funnel plot. Results: A total of 2864 patients with various cancers from 11 individual studies were enrolled. Results showed that elevated TG2 protein expression and mRNA expression could predict a shorter OS, with a combined HR of 1.93 (95% CI: 1.41–2.63) or HR of 1.95 (95% CI: 1.27–2.99), respectively. Moreover, data suggested that elevated TG2 protein expression was correlated with a shorter DFS (HR = 1.76, 95% CI: 1.36–2.29); whereas elevated TG2 mRNA expression was associated with a shorter DFS (HR = 1.71, 95% CI: 1.30–2.24). Conclusions: Our meta-analysis indicated that TG2 might serve as a promising biomarker of cancer prognosis.

Background: The ABO blood group system (ABO) plays a critical role in transfusion medicine and transplantation, with numerous subtypes exhibiting weakened antigen expression identified. This study reports a novel B subtype allele characterized by a previously unreported c.1A>G mutation in the ABO*B.01 allele, identified through clinical genomic analysis in a patient with serological ABO discrepancy. The aim is to highlight the molecular basis of this variant and its implications for accurate ABO typing. Case Description: In this study, we characterized a novel B subtype allele in a 54-year-old male patient presenting with ABO blood group discrepancy at Shandong Provincial Hospital, China. Comprehensive serological analysis demonstrated weak B antigen expression (1+ reaction strength) on erythrocytes with corresponding strong anti-A activity (4+) in plasma. The patient underwent surgery without requiring blood transfusion, as no significant hemorrhage occurred intraoperatively. Molecular characterization through complete sequencing of ABO gene exons 1–7 revealed a unique mutational profile: (I) a c.1A>G variant in exon 1; (II) compound mutations in exon 6 including a c.261delG (p.Thr88Profs31) frameshift mutation and c.297A>G substitution; and (III) multiple exon 7 variants (c.526C>G, c.657C>T, c.703G>A, c.796C>A, c.803G>C, and c.930G>A). Conclusions: This study reports a novel B subtype allele characterized by the c.1A>G variant on an ABO*B.01 background (GenBank accession number PP920240). The c.1A>G variant affects the translation initiation codon and is the primary finding defining this new allele, while the additional variants in exons 6 and 7 are consistent with the known ABO*O.01.01 and ABO*B.01 alleles. These findings highlight the need for genetic analysis in ABO typing to ensure transfusion safety. Further studies should characterize the functional effects of this variant.

The D−− phenotype is an extremely rare Rh blood group variant with absence of C, c, E, and e antigens but preserved D expression, predisposing to anti-Rh17 alloimmunization and hemolytic disease of fetus and newborn (HDFN). We report a 25-year-old Chinese woman (gravida 3, para 1) with D+C−c−E−e− phenotype and a history of severe neonatal jaundice and fetal demise. In her current pregnancy, admitted at 25 ⁺⁵ weeks for elevated fetal middle cerebral artery peak systolic velocity. PacBio sequencing (proband and her parents) and Oxford Nanopore whole-genome sequencing (ONT WGS; proband) were performed. PacBio sequencing preliminarily identified a compound heterozygous state at the RHCE locus involving two distinct RHCE -null haplotypes, a paternal complex structural variant and a maternal RHCE*02N.03 null allele with seven mutations. Subsequent ONT WGS resolved a novel paternal chimeric RHD–TMEM50A–RHCE rearrangement arising from dual recombination events. Serological and family evidence suggest that the maternal RHCE*02N.03 allele with c.486 + 1G>A results in a C−e− null phenotype in the compound heterozygous state. Four serial intrauterine transfusions used allogeneic D−− donor blood or maternal autologous washed irradiated packed red blood cells. All transfusions were well tolerated, with delivery at 37 weeks by cesarean section and favorable neonatal outcomes. This case demonstrates a sequential transfusion strategy for D−− pregnancies—prioritizing allogeneic D−− blood from rare donor networks when available, with maternal autologous blood as a safe alternative—and, through complementary PacBio and ONT WGS, adds evidence that complex RHD-RHCE inversion-recombination events may represent recurret mechanisms in the Chinese population while refining RHCE*02N.03 annotation from C− to C−e−.

Background: The RHD variant c.254C>A (p.Ala85Glu) has recently been associated with weak D expression. The aim of this study was to characterize the serologic and molecular findings in a Chinese family in which this variant is co-inherited with the RHD*03.02 allele, and to evaluate the phenotypic consequence of this compound heterozygous genotype. Methods: Blood samples and genomic DNA were obtained from the proband W322 and four relatives (W325–328). Rhesus D antigen (RhD) typing and antibody screening were performed using tube and gel-card assays. The coding region and exon-intron junctions of RHD were analyzed by polymerase chain reaction (PCR) and Sanger sequencing. Results: The proband W322 exhibited weak D antigen expression (tube 1+, gel card 2+), while his father W325 and son W328, carrying only the c.254C>A variant, showed moderate to strong reactivity (3–4+). His mother W326, carrying only the RHD*03.02 allele, also showed moderate reactivity (3–4+). An unaffected sister (W327) exhibited normal expression (tube 3+, gel 4+). Sequencing identified the heterozygous c.254C>A variant in the proband, his father, and son, and the RHD*03.02 allele in the proband and his mother. The proband is thus a compound heterozygote for both alleles. Conclusions: This family study describes a case of compound heterozygosity for RHD*c.254C>A and RHD*03.02 associated with a weak D phenotype. These findings highlight the importance of comprehensive RHD genotyping in cases with serologically weak D expression, particularly when routine testing yields ambiguous results.