Comparison of the Pathological Complete Response Rate and Survival Between HER2-Low and HER2-Zero Breast Cancer in Neoadjuvant Chemotherapy Setting: A Systematic Review and Meta-Analysis.

Although HER2-low breast cancer (BC) constitutes almost 50% of all BC types, its impact on the pathological complete response (pCR) rate and survival in early BC is uncertain. As a result, a systematic review was conducted to compare the pCR rate and survival of HER2-low and HER2-zero BC in the neoadjuvant chemotherapy (NACT) setting. Two reviewers independently performed literature searches using EMBASE, PubMed, and Cochrane Libraries internet databases up to June 2023. Finally, 29 studies with 178,294 patients were included. HER2-low BC had a considerably lower pCR rate compared to HER2-zero BC in the entire population (Risk Ratio [RR] = 0.68, P < .001) and in the hormone receptor (HR)-positive subgroup (RR = 0.73, P = .009), but not in the HR-negative subgroup (RR = 0.99, P = .755). Furthermore, patients with HER2-low BC exhibited prolonged disease-free survival (DFS) and overall survival (OS) compared to those with HER2-zero BC, observed in both the entire cohort (DFS: P = .004; OS: P = .008) and the HR-negative subgroup (DFS: P = .009; OS: P < .001). In the HR-positive population, OS was superior in HER2-low BC patients (P < .001), whereas no significant differences in DFS were observed (P = .064). Our findings imply that the pCR rate and prognosis of HER2-low BC are distinguished from those of HER2-zero BC in early BC treated with NACT, which contributes to a better knowledge of the BC subgroup.

Corrigendum: Comprehensive pan-cancer analysis of the prognostic and immunological roles of the METTL3/lncRNA-SNHG1/miRNA-140-3p/UBE2C axis.

[This corrects the article DOI: 10.3389/fcell.2021.765772.].

Identification and validation of tumor microenvironment-related signature for predicting prognosis and immunotherapy response in patients with lung adenocarcinoma.

Mounting evidence has found that tumor microenvironment (TME) plays an important role in the tumor progression of lung adenocarcinoma (LUAD). However, the roles of tumor microenvironment-related genes in immunotherapy and clinical outcomes remain unclear. In this study, 6 TME-related genes (PLK1, LDHA, FURIN, FSCN1, RAB27B, and MS4A1) were identified to construct the prognostic model. The established risk scores were able to predict outcomes at 1, 3, and 5 years with greater accuracy than previously known models. Moreover, the risk score was closely associated with immune cell infiltration and the immunoregulatory genes including T cell exhaustion markers. In conclusion, the TME risk score can function as an independent prognostic biomarker and a predictor for evaluating immunotherapy response in LUAD patients, which provides recommendations for improving patients' response to immunotherapy and promoting personalized tumor immunotherapy in the future.

LncRNA GSCAR promotes glioma stem cell maintenance via stabilizing SOX2 expression.

Gliomas are the most aggressive type of malignant brain tumors. Recent studies have demonstrated that the existence of glioma stem cells (GSCs) is critical for glioma recurrence, metastasis, and chemo- or radio-therapy resistance. Temozolomide (TMZ) has been used as an initial therapy for gliomas. However, the overall survival time is still limiting due to the lack of effective targets and treatment options. Therefore, identifying novel biomarkers for gliomas, especially for GSCs, is important to improve the clinical outcome in the future. In this study, we identify a human-specific long non-coding RNA (lncRNA, ENSG00000250377), termed GSCAR (glioma stem cell associated lncRNA), which is highly expressed in glioma cancerous tissues and cell lines. We reveal that GSCAR positively correlates with tumor grade. Glioma patients with GSCAR high expression exhibit shortened overall survival time, compared to patients with GSCAR low expression. Furthermore, we show that GSCAR knockdown by shRNAs or antisense oligonucleotide (ASO) reduces tumor cell proliferation, migration and xenograft tumor formation abilities. Mechanistic study shows that GSCAR acts as a ceRNA (competing endogenous RNA) for miR-6760-5p to promote the expression of oncogene SRSF1 (serine and arginine rich splicing factor 1). In addition, GSCAR mediates the protein complex formation between DHX9 (DExH-Box helicase 9) and IGF2BP2 (insulin-like growth factor 2 mRNA-binding protein 2), leading to the stabilization of SOX2 (sex-determining region Y-box 2) mRNA and then the transcriptional activation of GSCAR. Depleting GSCAR reduces SOX2 expression and GSC self-renewal ability, but promotes tumor cell responses to TMZ. These findings uncover that GSCAR/miR-6760-5p/SRSF1 axis and GSCAR/DHX9-IGF2BP2/SOX2 positive feedback loop are critical for glioma progression, which could be used as prognostic biomarkers and therapeutic targets in the future.

The function and clinical implication of YTHDF1 in the human system development and cancer.

YTHDF1 is a well-characterized m6A reader protein that is essential for protein translation, stem cell self-renewal, and embryonic development. YTHDF1 regulates target gene expression by diverse molecular mechanisms, such as promoting protein translation or modulating the stability of mRNA. The cellular levels of YTHDF1 are precisely regulated by a complicated transcriptional, post-transcriptional, and post-translational network. Very solid evidence supports the pivotal role of YTHDF1 in embryonic development and human cancer progression. In this review, we discuss how YTHDF1 influences both the physiological and pathological biology of the central nervous, reproductive and immune systems. Therefore we focus on some relevant aspects of the regulatory role played by YTHDF1 as gene expression, complex cell networking: stem cell self-renewal, embryonic development, and human cancers progression. We propose that YTHDF1 is a promising future cancer biomarker for detection, progression, and prognosis. Targeting YTHDF1 holds therapeutic potential, as the overexpression of YTHDF1 is associated with tumor resistance to chemotherapy and immunotherapy.

MCM4 is a novel prognostic biomarker and promotes cancer cell growth in glioma.

Background: Gliomas account for 75% of all primary malignant brain tumors in adults and result in high mortality. Accumulated evidence has declared the minichromosome maintenance protein complex (MCM) gene family plays a critical role in modulating the cell cycle and DNA replication stress. However, the biological function and clinic characterization of nine MCM members in low-grade glioma are not yet clarified. Methods: In this study, we utilized diverse public databases, including The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Rembrandt, Human Protein Atlas (HPA), Linkedomics, cbioportal, Tumor and Immune System Interaction Database (TISIDB), single-sample GSEA (ssGSEA), Tumor Immune Estimation Resource (TIMER), Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Therapeutics Response Portal databases to explore the mRNA and protein expression profiles, gene mutation, clinical features, diagnosis, prognosis, signaling pathway, tumor mutational burden (TMB), immune subtype, immune cell infiltration, immune modulator and drug sensitivity of nine MCMs. Afterward, qRT-PCR was utilized to detect the expression of the MCM family in glioblastoma multiforme (GBM) cell lines. The one-, three-, or five-year survival rate was predicted by utilizing a nomogram established by cox proportional hazard regression. Results: In this study, we found that nine MCMs were consistently up-regulated in glioma tissues and glioma cell lines. Elevated nine MCMs expressions were significantly correlated with a higher tumor stage, isocitrate dehydrogenase (IDH) mutates, 1p/19q codeletion, histological type, and primary therapy outcome. Survival analyses showed that higher expression of MCM2-MCM8 (minichromosome maintenance protein2-8) and MCM10 (minichromosome maintenance protein 10) were linked with poor overall survival (OS) and progression-free survival (PFS) in glioma patients. On the other hand, up-regulated MCM2-MCM8 and MCM10 were significantly associated with shorter disease-specific survival (DSS) in glioma patients. Univariate and multivariate analyses revealed that MCM2 (minichromosome maintenance protein2), MCM4 (minichromosome maintenance protein 4), MCM6 (minichromosome maintenance protein 6), MCM7 (minichromosome maintenance protein 7) expression and tumor grade, 1p/19q codeletion, age, and primary therapy outcome were independent factors correlated with the clinical outcome of glioma patients. More importantly, a prognostic MCMs model constructed using the above five prognostic genes could predict the overall survival of glioma patients with medium-to-high accuracy. Furthermore, functional enrichment analysis indicated that MCMs principal participated in regulating cell cycle and DNA replication. DNA copy number variation (CNV) and DNA methylation significantly affect the expression of MCMs. Finally, we uncover that MCMs expression is highly correlated with immune cell infiltration, immune modulator, TMB, and drug sensitivity. Conclusions: In summary, this finding confirmed that MCM4 is a potential target of precision therapy for patients with glioma.

A novel long noncoding RNA AC092718.4 as a prognostic biomarker and promotes lung adenocarcinoma progression.

Long noncoding RNAs (lncRNAs) reportedly play critical roles in the pathogenesis of various cancers, including lung adenocarcinoma (LUAD). However, the expression level, clinical significance, and potential function of lncRNA-AC092718.4 in LUAD remain unclear. In this study, we found that AC092718.4 was highly expressed in LUAD and high expression of AC092718.4 was correlated with poor overall survival (OS) and disease-specific survival (DSS) in LUAD. Cox regression analysis confirmed that AC092718.4 was an independent factor for LUAD prognosis. Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that AC092718.4 was involved in the PI3K-Akt signaling pathway, Th17 cell differentiation, and cell apoptosis. AC092718.4 expression was correlated with immune cell infiltration. Finally, we found that the knockdown of AC092718.4 inhibited lung adenocarcinoma (LUAD) cell growth and promote cell apoptosis. Our findings confirmed that AC092718.4 may serve as a potential prognostic biomarker in LUAD.

Corrigendum: Long non-coding RNA-TMPO-AS1 as ceRNA binding to let-7c-5p upregulates STRIP2 expression and predicts poor prognosis in lung adenocarcinoma.

[This corrects the article DOI: 10.3389/fonc.2022.921200.].

The function and clinical implication of circular RNAs in lung cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide. Despite the recent advent of promising new targeted therapies, lung cancer diagnostic strategies still have difficulty in identifying the disease at an early stage. Therefore, the characterizations of more sensible and specific cancer biomarkers have become an important goal for clinicians. Circular RNAs are covalently close, endogenous RNAs without 5' end caps or 3'poly (A) tails and have been characterized by high stability, abundance, and conservation as well as display cell/tissue/developmental stage-specific expressions. Numerous studies have confirmed that circRNAs act as microRNA (miRNA) sponges, RNA-binding protein, and transcriptional regulators; some circRNAs even act as translation templates that participate in multiple pathophysiological processes. Growing evidence have confirmed that circRNAs are involved in the pathogenesis of lung cancers through the regulation of proliferation and invasion, cell cycle, autophagy, apoptosis, stemness, tumor microenvironment, and chemotherapy resistance. Moreover, circRNAs have emerged as potential biomarkers for lung cancer diagnosis and prognosis and targets for developing new treatments. In this review, we will summarize recent progresses in identifying the biogenesis, biological functions, potential mechanisms, and clinical applications of these molecules for lung cancer diagnosis, prognosis, and targeted therapy.

Corrigendum: Comprehensive pan-cancer analysis of the prognostic and immunological roles of METTL3/lncRNA-SNHG1/miRNA-140-3p/UBE2C axis.

[This corrects the article DOI: 10.3389/fcell.2021.765772.].

Comprehensive analysis of DTYMK for estimating the immune microenvironment, diagnosis, prognosis effect in patients with lung adenocarcinoma.

The expression of deoxythymidylate kinase (DTYMK) is up-regulated in liver cancer. However, the underlying biological function and potential mechanisms of DTYMK driving the progression of lung adenocarcinoma remains unclear. In this study, we investigated the role of DTYMK in lung adenocarcinoma and found that the expression of DTYMK in LUAD tissues was significantly higher than that of DTYMK expression in adjacent normal tissues. Kaplan-Meier survival analysis showed that patients with higher DTYMK expression correlated with adverse prognosis. ROC curve analysis showed that the AUC value of DTYMK was 0.914. Correlation analysis showed that DTYMK expression was associated with immune infiltration in LUAD. Finally, we determine that DTYMK regulated cell proliferation, cell migration, and cell cycle of lung adenocarcinoma in vitro. In conclusion, our data demonstrated that DTYMK was correlated with progression and immune infiltration, and could serve as a prognostic biomarker for lung adenocarcinoma.

Corrigendum: identification and validation of lncRNA-SNHG17 in lung adenocarcinoma: a novel prognostic and diagnostic indicator.

[This corrects the article DOI: 10.3389/fonc.2022.929655.].

Identification and Validation of Long Non-Coding RNA LCIIAR as a Biomarker in LUAD.

Lung cancer is the leading cause of cancer-related death worldwide. Therapies for lung cancer have relatively poor outcomes and need to be improved. Lung cancer immune cell infiltration associated RNA (LCIIAR) is a long noncoding RNA (lncRNA), which is overexpressed in human cancers. However, the clinical significance and functional role of LCIIAR in Lung Adenocarcinoma remain unclear. Here, we identified a novel long non-coding RNA (ENSG00000256802), termed LCIIAR (lung cancer immune cell infiltration associated lncRNA), up-regulated in lung cancer tissue and cell lines. We show that increase LCIIAR expression correlated with poor clinical stage and adverse clinical outcomes and that could also serve as an independent unfavorable prognostic factor in patients with Lung Adenocarcinima. GSEA analysis demonstrated that LCIIAR is mainly involved in the regulation of the immune response. We uncovered that elevate LCIIAR expression positively correlated with immune infiltration and immune modulator in Lung Adenocarcinoma. More importantly, we confirmed that silencing of LCIIAR expression significantly inhibits the proliferation, and migration abilities of these tumour cells. We also demonstrated that the LCIIAR/hsa-miR184/SLC16A3/CDCP1 network regulates SLC16A3/CDCP1 overexpression in and is associated with poor prognosis in this tumour. Therefore our findings revealed the critical role of LCIIAR in Lung Adenocarcinoma progression, which may also serve as a prognostic biomarker and novel therapeutic target.

Long Non-Coding RNA-TMPO-AS1 as ceRNA Binding to let-7c-5p Upregulates STRIP2 Expression and Predicts Poor Prognosis in Lung Adenocarcinoma.

Background: Striatin-interacting protein 2 (STRIP2), also called Fam40b, has been reported to regulate tumor cell growth. But the role of STRIP2 in lung adenocarcinoma (LUAD) has not been discovered clearly. Thus, the aim of our study is to explore the function and underlying mechanism of STRIP2 in LUAD. Methods: Expression of STRIP2 was determined using the Cancer Genome Atlas (TCGA), GTEx, Ualcan, and the Human Protein Altas databases. The Correlation of STRIP2 and survival was detected by PrognoScan and Kaplan-Meier plotter databases. Besides, the correlation between STRIP2 expression and tumor immune infiltration as well as immune checkpoints were analyzed by the ssGSEA method. The biological function of STRIP2 and its co-expression genes was determined by gene ontology (GO) and Genes and Genomes (KEGG), respectively. Finally, the expression level and biological function of STRIP2 in LUAD were determined by qPCR, CCK8, transwell, and wound healing assays. Results: This manuscript revealed a significantly increased expression of mRNA and protein of STRIP2 in lung adenocarcinoma compared with the adjacent normal tissues. GEO and Kaplan-Meier plotter databases showed higher STRIP2 expression levels were correlated with poor prognosis survival of LUAD. Moreover, Cox regression analysis suggested that a higher STRIP2 level served as an independent risk factor in predicting deteriorative overall survival (OS) for LUAD patients. SsGSEA results showed STRIP2 expression level was positively correlated with infiltrating levels of Th2 cells in LUAD. Lastly, GO analysis indicated the biological processes were enriched in nuclear division and positive regulation of the cell cycle. KEGG signaling pathway analysis showed STRIP2 was correlated with the MAPK signaling pathway and the TNF signaling pathway. The GSEA database showed that STRIP2 was positively associated with the epithelial-mesenchymal transition, cell cycle, and TNF signaling pathway. The QRT-PCR assay showed that STRIP2 was upregulated in LUAD cell lines. Cell proliferation and migration were inhibited in LUAD by knockdown of STRIP2. Moreover, we confirmed that the TMPO-AS1/let-7c-5p/STRIP2 network regulates STRIP2 overexpression in LUAD and is associated with poor prognosis. Conclusion: Our findings indicated that STRIP2 acted as a crucial oncogene in LUAD and was correlated with unfavorable survival and tumor infiltration inflation.

Identifying Immune Cell Infiltration and Effective Diagnostic Biomarkers in Lung Adenocarcinoma by Comprehensive Bioinformatics Analysis and In Vitro Study.

Family with sequence similarity 72B (FAM72B) has been characterized in the regulation of neuronal development. Nevertheless, the prognostic value of FAM72B expression and its function in the immune microenvironment of lung adenocarcinoma (LUAD) currently remains elusive. In this study, by adopting bioinformatics methodology and experimental verification, we found that FAM72B was upregulated in lung cancer tissues and cell lines, and a higher FAM72B level predicted an unfavorable clinical outcome in LUAD patients. The knockdown of FAM72B significantly inhibited cell proliferation, cell migration, and induced cell apoptosis in LUAD. The receiver operating characteristic curve suggested that FAM72B had a high predictive accuracy for the outcomes of LUAD. Kyoto Encyclopedia of Genes and Genomes and Gene Set Enrichment Analyses confirmed that FAM72B-related genes were involved in cell proliferation and immune-response signaling pathway. Moreover, upregulated FAM72B expression was significantly associated with immune cell infiltration in the LUAD tumor microenvironment. Meanwhile, a potential ceRNA network was constructed to identify the lncRNA-AL360270.2/TMPO-AS1/AC125807.2/has-let-7a/7b/7c/7e/7f/FAM72B regulatory axis that regulates FAM72B overexpression in LUAD and is associated with a poor prognosis. We also confirmed that AL360270.2, TMPO-AS1, and AC125807.2 were significantly upregulated in LUAD cell lines than in human bronchial epithelial cells. In conclusion, FAM72B may serve as a novel biomarker in predicting the clinical prognosis and immune status for lung adenocarcinoma.

Pan-Cancer Integrated Analysis Identification of SASH3, a Potential Biomarker That Inhibits Lung Adenocarcinoma Progression.

Sterile alpha motif (SAM) and Src homology-3 (SH3) domain-containing 3 (SASH3) is an adaptor protein expressed mainly in lymphocytes, and plays significant roles in T-cell proliferation and cell survival. However, its expression level, clinical significance, and correlation with tumor-infiltrating immune cells across cancers remain unclear. In this study, we comprehensively examined the expression, dysregulation, and prognostic significance of SASH3, and the correlation with clinicopathological parameters and immune infiltration in pan-cancer. The mRNA and protein expression status of SASH3 were determined by TCGA, GTEx, and UALCAN. Kaplan-Meier analysis utilized the prognostic values of SASH3 in diverse cancers. The association between SASH3 expression and gene mutation, DNA methylation, immune cells infiltration, immune checkpoints, tumor mutation burden (TMB), and microsatellite instability (MSI) were analyzed using data from the TCGA database. High expression of SASH3 was not only linked to poor OS in ESCC, LAML, LGG, and UVM, but also associated with better OS in CESC, HNSC, LUAD, SARC, SKCM, THYM, and UCEC. As for DSS, a high level of SASH3 correlated with adverse DSS in ESCC, LGG, and UVM, and lowly expressed SASH3 was associated with shorter OS in CESC, HNSC, LUAD, SARC, SKCM, and UCEC. The results of Cox regression and nomogram analyses confirmed that SASH3 was an independent factor for LUAD prognosis. Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) results showed that SASH3 was involved in natural killer cell-mediated cytotoxicity, Th17 cell differentiation, PD-L1 expression and PD-1 checkpoint pathway in cancer, NF-kappa B signaling pathway, B-cell receptor signaling pathway, and Toll-like receptor signaling pathway. SASH3 expression was correlated with TMB in 28 cancer types and associated with MSI in 22 cancer types, while there was a negative correlation between SASH3 expression and DNA methylation in diverse human cancer. The high DNA methylation level of SASH3 was correlated with better OS in KIRC and UVM, and associated with poor OS in SKCM. Moreover, we uncover that SASH3 expression was positively associated with the stroma score in 27 cancer types, the microenvironment score, and immune score in 32 cancer types, 38 types of immune cells in 32 cancer types, the 45 immune stimulators, 24 immune inhibitors, 41 chemokines, 18 receptors, and 21 major histocompatibility complex (MHC) molecules in 33 cancer types. Finally, forced SASH3 expression inhibited lung adenocarcinoma (LUAD) cell proliferation and cell migration. Our findings confirmed that SASH3 may be a biomarker for the prognosis and diagnosis of human cancer.

Identification and Validation of lncRNA-SNHG17 in Lung Adenocarcinoma: A Novel Prognostic and Diagnostic Indicator.

Background: Lung cancer has the highest death rate among cancers globally. Accumulating evidence has indicated that cancer-related inflammation plays an important role in the initiation and progression of lung cancer. However, the prognosis, immunological role, and associated regulation axis of inflammatory response-related gene (IRRGs) in non-small-cell lung cancer (NSCLC) remains unclear. Methods: In this study, we perform comprehensive bioinformatics analysis and constructed a prognostic inflammatory response-related gene (IRRGs) and related competing endogenous RNA (ceRNA) network. We also utilized the Pearson's correlation analysis to determine the correlation between IRRGs expression and tumor mutational burden (TMB), microsatellite instability (MSI), tumor-immune infiltration, and the drug sensitivity in NSCLC. Growth curve and Transwell assay used to verify the function of SNHG17 on NSCLC progression. Results: First, we found that IRRGs were significantly upregulated in lung cancer, and its high expression was correlated with poor prognosis; high expression of IRRGs was significantly correlated with the tumor stage and poor prognosis in lung cancer patients. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment indicated that these IRRGs are mainly involved in the inflammatory and immune response-related signaling pathway in the progression of NSCLC. We utilized 10 prognostic-related genes to construct a prognostic IRRGs model that could predict the overall survival of lung adenocarcinoma (LUAD) patients possessing high specificity and accuracy. Our evidence demonstrated that IRRGs expression was significantly correlated with the TMB, MSI, immune-cell infiltration, and diverse cancer-related drug sensitivity. Finally, we identified the upstream regulatory axis of IRRGs in NSCLC, namely, lncRNA MIR503HG/SNHG17/miR-330-3p/regulatory axis. Finally, knockdown of SNHG17 expression inhibited lung adenocarcinoma (LUAD) cell proliferation and migration. Our findings confirmed that SNHG17 is a novel oncogenic lncRNA and may be a biomarker for the prognosis and diagnosis of LUAD. Conclusion: DNA hypomethylation/lncRNA MIR503HG/SNHG17/microRNA-330-3p/regulatory axis may be a valuable biomarker for prognosis and is significantly correlated with immune cell infiltration in lung cancer.

Immune-Related miRNA-195-5p Inhibits the Progression of Lung Adenocarcinoma by Targeting Polypyrimidine Tract-Binding Protein 1.

Purpose: Lung adenocarcinoma (LUAD) is the most common type of cancer and the leading cause of cancer-related death worldwide, resulting in a huge economic and social burden. MiRNA-195-5p plays crucial roles in the initiation and progression of cancer. However, the significance of the miRNA-195-5p/polypyrimidine tract-binding protein 1 (miRNA-195-5p/PTBP1) axis in the progression of lung adenocarcinoma (LUAD) remains unclear. Methods: Data were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The starBase database was employed to examine the expression of miRNA-195-5p, while the Kaplan-Meier plotter, UALCAN, and Gene Expression Profiling Interactive Analysis (GEPIA) databases were utilized to analyze the tumor stage and prognostic value of miRNA and PTBP1. Quantitative reverse transcription-polymerase chain reaction assay was conducted to detect the expression levels of miRNA-195-5p in LUAD cell lines and tissues. The effects of miRNA-195-5p on cell proliferation and migration were examined using the cell growth curve, clone information, transwell assays, and wound healing assays. Results: We found that miRNA-195-5p was down-regulated in LUAD cancer and cell lines. Importantly, its low levels were related to the tumor stage, lymph node metastasis, and poor prognosis in LUAD. Overexpression of miR-195-5p significantly inhibited cell growth and migration promotes cell apoptosis. Further study revealed that PTBP1 is a target gene of miRNA-195-5p, and overexpression of miRNA-195-5p inhibited the progression of LUAD by inhibiting PTBP1 expression. MiRNA-195-5p expression was related to immune infiltration in lung adenocarcinoma. Moreover, PTBP1 was negatively correlated with diverse immune cell infiltration and drug sensitivity. Conclusion: Our findings uncover a pivotal mechanism that miRNA-195-5p by modulate PTBP1 expression to inhibit the progression of LUAD. MiRNA-195-5p could be a novel diagnostic and prognostic molecular marker for LUAD.

Deciphering the Role of Shugoshin-Like Protein 1 in Lung Adenocarcinoma: A Comprehensive Analysis and In Vitro Study.

Shugoshin-like protein 1 (SGO1) has been characterized in its function in correct cell division and its role in centrosome cohesion in the nucleus. However, the underlying biological function and potential mechanisms of SGO1 driving the progression of lung adenocarcinoma remain unclear. In this study, we found that SGO1 was increased in LUAD tissues and cell lines. Upregulation of SGO1 expression was correlated with poor overall survival (OS), disease-free survival (DSS), and progression-free survival (PFS) in patients with LUAD. ROC curve analysis suggested that the AUC value of SGO1 was 0.983. Correlation analysis showed that SGO1 expression was related to immune infiltration in LUAD. Meanwhile, a potential ceRNA network was constructed to identify the lncRNA-MIR4435-2HG/miR-125a-5p/SGO1 regulatory axis in LUAD. Finally, we determine that SGO1 regulated the cell proliferation and cell apoptosis of lung adenocarcinoma in vitro. In conclusion, our data suggested that SGO1 could be a novel prognostic biomarker for lung adenocarcinoma.

Heterogeneity of the tumor immune microenvironment and its clinical relevance.

During the course of tumorigenesis and subsequent metastasis, malignant cells gradually diversify and become more heterogeneous. Consequently, the tumor mass might be infiltrated by diverse immune-related components, including the cytokine/chemokine environment, cytotoxic activity, or immunosuppressive elements. This immunological heterogeneity is universally presented spatially or varies temporally along with tumor evolution or therapeutic intervention across almost all solid tumors. The heterogeneity of anti-tumor immunity shows a profound association with the progression of disease and responsiveness to treatment, particularly in the realm of immunotherapy. Therefore, an accurate understanding of tumor immunological heterogeneity is essential for the development of effective therapies. Facilitated by multi-regional and -omics sequencing, single cell sequencing, and longitudinal liquid biopsy approaches, recent studies have demonstrated the potential to investigate the complexity of immunological heterogeneity of the tumors and its clinical relevance in immunotherapy. Here, we aimed to review the mechanism underlying the heterogeneity of the immune microenvironment. We also explored how clinical assessments of tumor heterogeneity might facilitate the development of more effective personalized therapies.