The role of adjuvant chemotherapy (adj-CT) in stage II colon cancer remains controversial. Circulating tumor DNA (ctDNA) is a promising biomarker for detecting minimal residual disease (MRD) and predicting recurrence. This systematic review and meta-analysis evaluated the prognostic value of ctDNA in stage II colorectal cancer (CRC), focusing on postoperative detection, post adj-CT outcomes, and dynamic surveillance. A literature search identified studies correlating ctDNA positivity in stage II CRC with recurrence risk, recurrence-free survival (RFS), and disease-free survival (DFS). Seven studies met the inclusion criteria. Postoperative ctDNA positivity significantly increased the risk of recurrence (pooled risk ratio [RR:] 3.66; 95% confidence interval [CI]: 1.25-10.72; p = 0.002). CtDNA positivity after adj-CT was strongly associated with poor survival, while dynamic ctDNA monitoring detected recurrence earlier than conventional methods, including carcinoembryonic antigen (CEA) and imaging. CtDNA is a robust prognostic biomarker in stage II CRC, enabling personalized treatment. High-risk ctDNA-positive patients may benefit from intensified therapy, while ctDNA-negative patients could avoid unnecessary treatments. However, the standardization of detection methods and large-scale validation studies are needed before integrating ctDNA into routine clinical practice as a non-invasive, dynamic tool for personalized care.

CD44 is a promising target in the prognosis and treatment of non-small cell lung cancer (NSCLC). The study deals with systematic review and meta-analysis to determine the association between CD44 overexpression and survival and clinicopathological characteristics in NSCLC patients.

Galectin-9 (Gal-9) has gained increasing attention in recent years in the field of cancer immunology. Its interactions with various immune cell types in the tumor microenvironment influence tumor progression, making it a novel target for immunotherapy. Despite its potential as a therapeutic target, the prognostic significance of Gal-9 in tumor cells remains unclear. Conflicting data exists on its expression levels and outcomes, prompting a comprehensive review and meta-analysis to elucidate its independent prognostic role across different cancer types. This study aims to examine the varying effects of Gal-9 expression across various cancer subtypes, providing insights into its potential as a prognostic marker and highlighting its significance in the realm of cancer treatment. To assess the prognostic significance of Gal-9 expression in cancer, we conducted a comprehensive database search across PubMed, Embase, and Web of Science, incorporating studies published until December 2024, regardless of language. Using pooled hazard ratios (HRs) with 95% confidence intervals (CIs), we evaluated the role of Gal-9 expression in predicting cancer outcomes across various cancer types. Our analysis encompassed 29 studies with a total of 4,720 patients to investigate the prognostic significance of Gal-9 expression across different cancer types. The results demonstrated that elevated Gal-9 expression was significantly associated with improved overall survival (OS) in solid tumors, with a pooled hazard ratio of 0.75 (95% CI: 0.63-0.90, p =  0.002). No statistically significant correlation was observed between Gal-9 expression and cancer recurrence (HR =  0.88, 95% CI: 0.65-1.19, p =  0.42). Conversely, in hematological cancers, high Gal-9 expression correlated with more rapid disease progression, as reflected by progression-free survival (PFS) or time to treatment (TTT) (HR =  2.29, 95% CI: 1.26-4.16, p =  0.007). The subgroup analyses further revealed that higher Gal-9 expression was associated with OS in gastrointestinal and urological cancers and was linked to disease-free survival (DFS) and recurrence-free survival (RFS) in hepatobiliary and urological cancers. Our research has uncovered that Gal-9 serves as a promising prognostic indicator for solid tumors, offering valuable insights into patient outcomes. High levels of Gal-9 expression within gastrointestinal, hepatobiliary, and urological cancers have been linked to better prognoses, while its presence in hematological cancers is associated with poorer outcomes. These contrasting findings emphasize the importance of interpreting biomarkers with careful consideration to the specific context. Moreover, our study sheds light on the diverse physiological roles of intracellular and secreted Gal-9, highlighting the intricate ways in which this protein influences cancer progression.

Distinct subgroups of rare brain tumors can be molecularly classified using whole genome DNA methylation profiling and next-generation sequencing. Furthermore, these tools can identify germline mutations contributing to carcinogenesis. Access to molecular testing in the clinical setting is vital for pathology laboratories to make an accurate diagnosis. One molecularly unique brain tumor requiring such tools is the papillary tumor of the pineal region (PTPR). Herein, we present a case report of a 21-year-old male presenting with macrocephaly and obstructive hydrocephalus due to the PTPR. Next-generation sequencing identified a pathogenic PTEN p.G132D mutation in the tumor and matched germline findings further identified PTEN Hamartoma Tumor Syndrome (PHTS). The case report tumor was initially misdiagnosed as ependymoma while methylation profiling classified it more specifically as a PTPR, Group B. To better understand the current status of PTPRs, we conducted a systematic review of recent cases reporting on the diagnostics, treatments, and outcomes for PTPR patients. To our knowledge, this is the first case report for PTPRs revealing an association with PHTS. Our review revealed inconsistencies in diagnostics, treatments, and outcomes for PTPR, and an underutilization of definitive molecular testing.

Lynch syndrome is an autosomal dominant genetic disorder associated with early-onset colorectal cancer (CRC), endometrial cancer and other malignancies. This condition is defined by deficient DNA mismatch repair and high microsatellite instability (dMMR/MSI-high), exhibiting a substantial response to immunotherapy. However, microsatellite-stable (MSS) tumours may infrequently occur in individuals with Lynch syndrome. Our aim was to evaluate the efficacy of immunotherapy in patients with Lynch Syndrome and dMMR/MSS colorectal cancer.

The disease shift of chronic lymphocytic leukemia (CLL) to diffuse large B-cell lymphoma (DLBCL), so-called Richter transformation (RT), is a catastrophic clinical event. Rarely, survival can outperform expectations and accurate prognostication for patients may affect therapeutic choices. To date, prognosis has relied on readily available factors such as TP53 disruption, previous CLL treatment status, and performance score. Recently, a shared clonality assessment by immunoglobulin heavy-chain variable region gene (IgHV) sequencing of the CLL and RT has been considered therapeutically relevant, but this is infrequently performed. We performed a systematic review of peer-reviewed manuscripts where outcomes in relation to clonal relatedness and lack thereof (clonally related and clonally unrelated RT-DLBCL) were examined. Fifteen manuscripts that included 336 patients were found, of which 6 compared survival outcomes between the 2 groups in a statistically meaningful way. Two analyses showed no difference in survival outcomes with 4 studies reporting a significantly poorer prognosis with clonally related RT-DLBCL. In 2 of these studies, the baseline characteristics of clonally related and clonally unrelated groups were compared and the clonally related cases were enriched for underlying CLL, which was TP53 disrupted, IgHV unmutated, more heavily pretreated, and exhibiting stereotyped B-cell receptor VH CDR3 and RT-DLBCL, which was MYD88 wild type. We demonstrate that although clonal relatedness of the underlying CLL confers a poorer survival, this is not demonstrated in any study to be independent of other well-described clinical and genomic variables known to influence outcomes in RT-DLBCL. Further independent validation of this prognostic factor is required to help guide universal adoption into clinical practice.

Matched targeted therapies (MTT) given alone or in combination with systemic anti-cancer therapies have delivered proven survival benefit for many people with newly diagnosed cancer. However, there is little evidence of their effectiveness in the recurrent or late-stage setting. With this uncertainty, alongside the perception that late-stage cancers are too genetically heterogenous or too mutationally diverse to benefit from matched targeted therapies, next-generation sequencing (NGS) of tumours in people with refractory cancer remains a low priority. As a result, next-generation sequencing testing of recurrent or late-stage disease is discouraged. We lack evidence to support the utility of next generation sequencing in guiding matched targeted therapies in this setting.

Phosphatase and tensin homolog hamartoma tumor syndrome (PTEN Syndrome), an autosomal dominant group of disorders caused by PTEN dysregulation, predisposes patients to hamartomas, lipomas, vascular tumors/malformations, and potential malignancies. A link between PTEN syndrome and early onset enlargement of tonsillar tissue has been described. Presented is the case of a child with PTEN syndrome who experienced spontaneous tonsillar hemorrhage (STH), followed by a systematic review of the literature.

Accurately distinguishing between multiple primary lung cancers (MPLC) and intrapulmonary metastasis (IPM) is crucial for tailoring treatment strategies and improving patient outcomes. While molecular methods offer significant advantages over traditional clinical-pathological evaluations, they lack standardized diagnostic protocols and validated prognostic value. This study systematically compared the diagnostic and prognostic performance of molecular methods versus clinical-pathological evaluations in diagnosing multiple lung cancers (MLCs), specifically focusing on the impact of next-generation sequencing (NGS) parameters on diagnostic accuracy. A review of 41 studies encompassing 1266 patients revealed that two molecular methods, Mole1 (manually counting shared mutations) and Mole2 (bioinformatics-assisted clonal probability calculation), both demonstrated superior diagnostic accuracy and prognostic discrimination capabilities. Molecular assessment, particularly Mole1, effectively stratified prognosis for MPLC and IPM, leading to significantly improved disease-free survival (DFS: HR = 0.24, 95% CI: 0.15-0.39) and overall survival (OS: HR = 0.33, 95% CI: 0.18-0.58). Further analysis suggests that a minimal panel of 30-50 genes may be sufficient to effectively differentiate prognoses. Compared to Mole1, Mole2 demonstrated greater specificity and stability across various panels, achieving AUC values from 0.962 to 0.979. Clinical-pathological evaluations proved unreliable, not only failing to distinguish prognosis effectively but also exhibiting a potential misdiagnosis rate of 35.5% and 33.6% compared to the reference diagnosis. To improve both cost-effectiveness and diagnostic accuracy, bioinformatics-assisted molecular diagnostics should be integrated into multidisciplinary assessments, especially for high-risk cases where diagnostic errors are common.

Patients with colorectal cancer (CRC) who have KRAS mutations often see poor results with standard treatments, leaving them with fewer viable options. Over the past few years, new KRAS G12C inhibitors have emerged as a targeted approach for a specific subset of these mutations, though their effectiveness and safety in advanced CRC remain areas of ongoing research. In this systematic review, we identified nine clinical trials including a total of 668 patients, by searching PubMed, Web of Science, CENTRAL, and Embase through October 2024. When sotorasib was used alone, the objective response rate (ORR) ranged from 7.1 to 9.7%, with disease control (DC) rates of 73.8 to 82.3% and a median progression-free survival (PFS) spanning 4-5.6 months. Combining sotorasib with panitumumab, especially at higher doses, raised its ORR to 26.4%. Meanwhile, pairing adagrasib with cetuximab led to a 42% ORR and a median PFS of 6.9 months, surpassing the 19% ORR observed with adagrasib alone. Divarasib monotherapy produced a 36% ORR and an 85.5% DC rate, with a PFS of 5.6 months; in tandem with cetuximab, those numbers climbed to a 62.5% ORR and a PFS of 8.1 months. Common side effects across these trials included diarrhea, nausea, fatigue, and various skin reactions. Overall, KRAS G12C inhibitors appear to offer meaningful benefits for CRC patients, particularly when used alongside EGFR inhibitors like cetuximab or panitumumab. However, further large-scale, randomized trials are needed to refine dosing strategies and gain a clearer picture of both efficacy and potential risks.

Recently, we and others have demonstrated the involvement of Zinc Finger Antisense 1 (ZFAS1) in cancer development. However, the intricate interplay of ZFAS1 with miRNAs and mRNAs remains to be fully understood.

Currently, the primary methods for detecting HER2 expression levels are immunohistochemistry (IHC) and in situ hybridization (ISH), with the traditional standard being a HER2-positive score of 3 + accompanied by ERBB2 gene amplification detected through ISH. However, a new entity has recently emerged: HER2-low, defined as HER2 IHC 1 + or 2 + with negative ISH. HER2-low breast cancer, representing 45-60% of all HER2-negative tumors, has distinct biological characteristics and uncertain responses to conventional HER2-targeted therapies. Recent studies suggest varied clinical outcomes, highlighting the need for further investigation into the impact of HER2-low status on treatment efficacy and prognosis.

Acute myeloid leukemia (AML) prognosis is affected by unique factors to each individual and studies have indicated that dysregulated expression of circRNAs may serve as prognostic biomarkers for AML. Therefore, we conducted this study to assess the prognostic value of circRNAs expression and it's correlation with clinicopathological features. Comprehensive search was conducted in WOS, Scopus, PubMed, Google Scholar, ProQuest, and grey literature. The certainty of evidence was assessed using the modified GRADE approach for prognostic and clinicopathological meta-analysis. The hazard ratio (HR) was employed to assess the prognostic value of dysregulated expression of circRNAs in patient survival, while the risk ratio (RR) was utilized to analyze the correlation between circRNAs and clinicopathological features. Our results demonstrated that dysregulation of circRNAs expression was associated with poor prognosis related to overall survival (OS) indicator (HR:2.05; 95%CI: 1.75-2.40) and also related to non-OS indicators such as (EFS, LFS, RFS, and DFS) (HR:2.09, 95%CI: 1.47-2.97). Priori and post-hoc subgroup analysis was conducted to describe variables that potentially affected heterogeneity and effect size. We also evaluated the association between dysregulated expression of circRNAs and 19 clinicopathological parameters. Our results show that there is significant relationship between the dysregulated expression of circRNAs and the mentioned parameters: type M6 vs. other types (RR:1.51, 95% CI:1.12-2.03), FLT3-ITD mutation (RR:1.17, 95%CI: 1.00-1.36), and risk status (RR:1.35, 95% CI: 1.13-1.60). This systematic review and meta-analysis suggest that the investigation of circRNAs expression changes can serve as valuable biomarkers for the assessment of prognosis in AML patients.

Head and Neck Squamous Cell Carcinoma (HNSCC) is a heterogeneous group of malignancies with poor survival outcomes, particularly in advanced stages. Identifying prognostic biomarkers could help improve patient management. miR-375, a small non-coding RNA, has been shown to influence tumor growth and immune responses, making it a candidate biomarker. This study aims to evaluate the role of miR-375 expression in predicting survival outcomes in HNSCC patients. A systematic review and meta-analysis were conducted according to PRISMA guidelines, incorporating data from six studies and the TGCA cohort, encompassing 452 patients. Fixed-effects models were applied to calculate aggregated hazard ratios (HRs) for overall survival (OS). Kaplan-Meier curves were analyzed using the Tierney method, and Trial Sequential Analysis (TSA) was performed to assess statistical power. Low miR-375 expression was associated with poorer OS, with an aggregated HR of 1.23 (95% CI: 1.10-1.37). Subgroup analysis showed consistent trends across oral and laryngeal squamous cell carcinoma. Sensitivity analysis confirmed these findings. TSA revealed that although the number of patients was sufficient, statistical power was insufficient to confirm a predefined risk reduction ratio (RRR) of 49%. Data from the TGCA cohort supported the meta-analysis findings, with an HR for OS of 1.32 (95% CI: 0.96-1.8). Low miR-375 expression is associated with worse survival outcomes in HNSCC patients, indicating its potential as a prognostic biomarker and therapeutic target. However, the retrospective nature of the included studies underscores the need for prospective research to validate these findings.

Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and carries a worse prognosis relative to other breast cancer subtypes. This systematic review and meta-analysis evaluated the prognostic value of circulating tumor DNA (ctDNA) in early-stage TNBC.

Breast and ovarian cancers are significant global health challenges, with inherited variations in breast cancer gene 1 (BRCA1) and breast cancer gene 2 (BRCA2) substantially increasing the risk, aggressiveness, and early onset of these diseases. This work aimed to examine pathogenic variants (PVs) in BRCA1 and BRCA2 databases that include Mexican populations. A systematic review of literature and data mining spanning from 2002 to 2023 was conducted. Articles published in journals indexed in SCImago quartiles Q1 to Q4 were screened. Databases were paired, standardized, and enriched with data from reputable global platforms: Genome Data Viewer, dbSNP, ClinVar, gnomAD browser, Breast Cancer Information Core (BIC), ClinGen, Varsome, Human Genome Variation Society (HGVS), Bioproject, Ensembl, Gene NIH NCIB, UniProt, and BRCA Exchange. Outcomes included data from 9,026 Mexican genotypes, identifying 657 PVs. Genetic mapping revealed certain exons, notably exon 10 of BRCA1 and exon 11 of BRCA2, as highly mutagenic hot spots. The most frequent alteration was a large deletion in BRCA1 (ex9-12del), associated with a founder effect originating from a common Mexican ancestor. Finally, we constructed a genetic map containing all the single nucleotide variants (SNVs) and large rearrangements presented in the analyzed databases.

A growing number of systematic bioinformatics analyses were conducted to investigate the mechanism of interaction between long non-coding RNA (lncRNA) and endometrial carcinoma (EC) to predict the prognosis. However, there is no evidence-based evidence that abnormal lncRNA expression is strongly associated with the pathological characteristics and prognosis of EC patients. In this meta-analysis, we systematically evaluated the relationship between upregulated lncRNA expression levels and clinicopathological features, five-year survival rate, and progression-free survival (PFS).

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide and is often diagnosed at advanced stages, limiting treatment options. This systematic review aims to evaluate the efficacy of liquid biopsy in detecting genetic mutations in NSCLC, focusing on its sensitivity, specificity, clinical utility, and potential to guide personalized treatment strategies.

Li-Fraumeni Syndrome (LFS) is a rare hereditary cancer syndrome characterized by an increased risk of early-onset and multiple tumors across various organ systems, predominantly linked to germline TP53 mutations. While commonly associated neoplasms include sarcomas, breast cancer, and adrenocortical carcinoma, the occurrence of high-grade gliomas (HGG), including glioblastoma multiforme (GBM), in LFS patients is less documented and typically presents at a younger age relative to sporadic cases. A systematic review following PRISMA guidelines was conducted, focusing on clinical studies and case reports that explore the association between HGG and LFS. A comprehensive PubMed search was used to capture relevant studies. The inclusion criteria focused on patients with a confirmed diagnosis of LFS and histopathologically verified HGG. A total of 248 articles were initially identified, with 8 studies meeting the final inclusion criteria after independent review and consensus. Overall, 8 studied reported on patients with either WHO grade 3 or 4 gliomas in the setting of LFS. In total these studies represent 12 patients, with 8 (66%) WHO grade 4, and 4 (33%) WHO grade 3. 9 (75%) patients underwent maximal safe resection, 5 (42%) underwent concurrent TMZ and EBRT. 9 (75%) patients underwent external beam radiation therapy (EBRT), 1 (8%) underwent intensity modulated radiation therapy (IMRT), and 1 (8%) underwent adjuvant treatment with tumor treating fields (TTF) therapy. Overall chemotherapy utilization was 75% with 9 patients receiving some form of chemotherapy. The median time to recurrence following initial treatment was 7 months (IQR: 2.00-7.00). Time to progression was variable, ranging from 5.1 months to 7 years. 64% of patients succumbed to their disease with a median OS of 17 months across studies. LFS associated HGGs are a genetically heterogenous entity. Detailed study of outcomes reported in the literature with respect to these genetics will develop further insight into therapeutic response and prognostication.

Cancer incidence is rising globally, particularly in aging populations. Understanding the genetic, cellular, and molecular mechanisms underlying cancer is crucial for developing effective interventions. Dead-end protein 1 (DND1), an RNA-binding protein, plays a pivotal role in germ cell regulation and tumorigenesis. This systematic review investigates DND1's multifaceted roles in cancer progression and evaluates its interactions and potential as a therapeutic target. A systematic search of four databases (Web of Science, MEDLINE via PubMed, Scopus, and Embase) yielded 436 unique records. After screening, 38 studies were included for data extraction. STRING-based network analysis identified key interactors-including NANOS1-3, TDRD7, DAZL, and EIF2S2- and pathways associated with RNA binding, translational regulation, and apoptosis. DND1 demonstrates dual, context-dependent roles as both a tumor suppressor and promoter. Its regulation of miRNAs and interaction with germ cell-specific proteins emerged as critical mechanisms in tumor suppression and progression. This study highlights DND1's central role in cancer biology, with significant implications for diagnostics and therapeutics. The findings provide a robust foundation for experimental validation of key interactions and further exploration of DND1's molecular mechanisms. The dual functionality of DND1 as a tumor suppressor and promoter underscores its potential as a target for novel cancer therapies, particularly for germ cell tumors and other cancers.