Cascading Detection of Hydrogen Sulfide and N-Acetyltransferase 2 in Hepatocellular Carcinoma Cells Using a Two-Photon Fluorescent Probe.

Hydrogen sulfide (H2S), a critical gas signaling molecule, and N-acetyltransferase 2 (NAT2), a key enzyme in drug metabolism, are both known active biomarkers for liver function. However, the interactions and effects of H2S and NAT2 in living cells or lesion sites remain unknown due to the lack of imaging tools to achieve simultaneous detection of these two substances, making it challenging to implement real-time imaging and precise tracking. Herein, we report an activity-based two-photon fluorescent probe, TPSP-1, for the cascade detection of H2S and NAT2 in living liver cells. Continuous conversion from TPSP-1 to TPSP-3 was achieved in liver cells and tissues. Significantly, leveraging the outstanding optical properties of this two-photon fluorescent probe, TPSP-1, has been effectively used to identify pathological tissue samples directly from clinical liver cancer patients. This work provides us with this novel sensing and two-photon imaging probe, which can be used as a powerful tool to study the physiological functions of H2S and NAT2 and will help facilitate rapid and accurate diagnosis and therapeutic evaluation of hepatocellular carcinoma.

Pan-cancer and single-cell analysis reveal THRAP3 as a prognostic and immunological biomarker for multiple cancer types.

Background: Thyroid hormone receptor-associated protein 3 (THRAP3) is of great significance in DNA damage response, pre-mRNA processing, and nuclear export. However, the biological activities of THRAP3 in pan-cancer remain unexplored. We aimed to conduct a comprehensive analysis of THRAP3 and validate its expression levels in lung cancer. Methods: A pan-cancer analysis was conducted to study the correlation of THRAP3 expression with clinical outcome and the tumor microenvironment based on the available bioinformatics databases. The protein levels of THRAP3 were explored in lung cancer by immunohistochemistry (IHC) analysis. Single-cell sequencing (ScRNA-seq) analysis was employed to investigate the proportions of each cell type in lung adenocarcinoma (LUAD) and adjacent normal tissues, along with the expression levels of THRAP3 within each cell type. Results: THRAP3 is upregulated in multiple cancer types but exhibits low expression in lung squamous cell carcinoma (LUSC). immunohistochemistry results showed that THRAP3 is a lowly expression in LUAD and LUSC. THRAP3 elevation had a poor prognosis in kidney renal clear cell carcinoma and a prolonged survival time in kidney chromophobe, brain lower-grade glioma and skin cutaneous melanoma, as indicated by the KM curve. Single-cell analysis confirmed that the proportions of T/B cells, macrophages, and fibroblasts were significantly elevated in LUAD tissues, and THRAP3 is specifically overexpressed in mast cells. Conclusion: Our findings uncover that THRAP3 is a promising prognostic biomarker and immunotherapeutic target in multiple cancers, but in LUAD and LUSC, it may be a protective gene.

Percutaneous Image-Guided Microwave Ablation for Treating Postsurgical Intrapulmonary Oligometastases or Oligorecurrence.

OBJECTIVE: To assess the clinical efficacy of microwave ablation (MWA) in treating tumour patients with postsurgical intrapulmonary oligometastases or oligorecurrence (PIORO). STUDY DESIGN: Descriptive study. Place and Duration of the Study: Departments of Thoracic Surgery and Oncology, Jinan Central Hospital and Qilu Hospital, Jinan, China, from January 2014 to June 2023. METHODOLOGY: Clinical data of 31 patients with PIORO receiving treatment with MWA were retrospectively analysed. After undergoing MWA, the patients were followed up for computed tomography (CT) examination on the 7th day, 1st month, and every 3 months, respectively. The Kaplan-Meier method was conducted to evaluate the clinical outcomes; overall survival (OS), progression-free survival (PFS), and time to local progression (TTLP). RESULTS: All patients with PIORO were successfully treated with MWA. The 3-year survival rate of patients was 35.5%. The median OS was 26.0 months, the median PFS was 11.1 months, and the median TTLP was 14.4 months. Patients with oligometastatic or oligorecurrent tumours ≤3 cm in diameter showed better PFS (≤3 cm, 14.261 m vs. >3 cm, 7.786 m; p <0.01) and TTLP (≤3 cm, 19.522 m vs. >3 cm, 12.214 m; p <0.05) than those with tumours >3 cm in diameter. Clinical characteristics of the patients were not significantly correlated with OS. CONCLUSION: MWA, as a topically therapeutic method, is an effective procedure for tumour patients with PIORO, especially in cases of oligometastatic or oligorecurrent tumours ≤3 cm in diameter. KEY WORDS: Microwave ablation, Thermal ablation, Oligometastases, Oligorecurrence, Progression-free survival, Survival.

Advancements in colorectal cancer research: Unveiling the cellular and molecular mechanisms of neddylation (Review).

Neddylation, akin to ubiquitination, represents a post­translational modification of proteins wherein neural precursor cell­expressed developmentally downregulated protein 8 (NEDD8) is modified on the substrate protein through a series of reactions. Neddylation plays a pivotal role in the growth and proliferation of animal cells. In colorectal cancer (CRC), it predominantly contributes to the proliferation, metastasis and survival of tumor cells, decreasing overall patient survival. The strategic manipulation of the NEDD8­mediated neddylation pathway holds immense therapeutic promise in terms of the potential to modulate the growth of tumors by regulating diverse biological responses within cancer cells, such as DNA damage response and apoptosis, among others. MLN4924 is an inhibitor of NEDD8, and its combined use with platinum drugs and irinotecan, as well as cycle inhibitors and NEDD activating enzyme inhibitors screened by drug repurposing, has been found to exert promising antitumor effects. The present review summarizes the recent progress made in the understanding of the role of NEDD8 in the advancement of CRC, suggesting that NEDD8 is a promising anti­CRC target.

Cellular and molecular mechanisms of oroxylin A in cancer therapy: Recent advances.

Seeking an effective and safe scheme is the common goal of clinical treatment of tumor patients. In recent years, traditional Chinese medicine has attracted more and more attention in order to discover new drugs with good anti-tumor effects. Oroxylin A (OA) is a compound found in natural Oroxylum indicum and Scutellaria baicalensis Georgi plants and has been used in the treatment of various cancers. Studies have shown that OA has a wide range of powerful biological activities and plays an important role in neuroprotection, anti-inflammation, anti-virus, anti-allergy, anti-tumor and so on. OA shows high efficacy in tumor treatment. Therefore, it has attracted great attention of researchers all over the world. This review aims to discuss the anti-tumor effects of OA from the aspects of cell cycle arrest, induction of cell proliferation and apoptosis, induction of autophagy, anti-inflammation, inhibition of glycolysis, angiogenesis, invasion, metastasis and reversal of drug resistance. In addition, the safety and toxicity of the compound were also discussed. As a next step, to clarify the benefits and adverse effects of Oroxylin A in cancer patients further experiments, especially clinical trials, are needed.

ZNF217: An Oncogenic Transcription Factor and Potential Therapeutic Target for Multiple Human Cancers.

Zinc finger protein 217 (ZNF217) is one of the well-researched members of the Krüppel-like factor transcription factor family. ZNF217 possesses a characteristic structure of zinc finger motifs and plays a crucial role in regulating the biological activities of cells. Recent findings have revealed that ZNF217 is strongly associated with multiple aspects of cancer progression, impacting patient prognosis. Notably, ZNF217 is subject to regulation by non-coding RNAs, suggesting the potential for targeted manipulation of such RNAs as a robust therapeutic avenue for managing cancer in the future. The main purpose of this article is to provide a detailed examination of the role of ZNF217 in human malignant tumors and the regulation of its expression, and to offer new perspectives for cancer treatment.

A retrospective study on the efficacy and safety of Endostar with chemotherapy in EGFR-TKI-resistant NSCLC.

BACKGROUND: Endostar is a strong angiogenesis inhibitor that is effective in treating non-small cell lung cancer (NSCLC), but the effect of Endostar in the treatment of patients with EGFR-TKI-resistant NSCLC remains unclear. We evaluated the clinical efficacy and safety of Endostar in EGFR-mutant NSCLC patients resistant to EGFR inhibition treatment. METHODS: From January 1, 2016 to June 30, 2018, 68 patients were selected from the 4 institutions for the study. Patients with NSCLC received Endostar plus chemotherapy every 21-day cycle. Chemotherapy types included platinum-containing dual drugs and platinum-free single drugs. Endostar was administered by intermittent intravenous infusion or continuous microinfusion pump infusion. The overall response rate (ORR), disease control rate (DCR) and adverse events were analyzed. Survival of patients was also evaluated. RESULTS: For all patients, the median progression-free survival (PFS) was 2.8 months, and the median overall survival (OS) was 14.2 months. PFS and OS in the Endostar pump continuous group were better than those in the Endostar intravenous infusion group. The disease control rate (DCR) was 79.4%. A total of 28 (41.2%) patients experienced varying grades of adverse events during treatment. No treatment-associated deaths were observed. The grade 3 treatment-emergent adverse events (TEAEs) were myelosuppression, weakness, and nausea/vomiting. CONCLUSIONS: Endostar was effective and well tolerated in advanced NSCLC patients. Endostar treatment showed promising survival results in EGFR-mutant NSCLC patients.

Recent Advances in Natural Products with Anti-Leukemia and Anti-Lymphoma Activities.

Leukemia and lymphoma are the most common blood cancers, which pose a critical threat to the health of adults and children. The total incidence and mortality rates of both are approximately 6% globally. Compared with the expensive cost of CAR T cell therapy, natural products from animals, plants and microorganisms have the characteristics of wide-range sources and costeffectiveness in the treatment of cancer. Moreover, the drug resistance that emerged in leukemia and lymphoma treatments shows an urgent need for new drugs. However, in addition to the natural products that have been marketed in the treatment of leukemia and lymphoma, there have been a large number of studies on natural products that fight blood cancer in recent years. This review summarized the recent studies on natural compounds with anti-lymphoma and anti-leukemia activities, hoping to provide novel weapons into the drug development arsenal.

The effectiveness of problem-based learning compared with lecture-based learning in surgical education: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis was conducted to systematically evaluate the impact of problem-based learning (PBL) and lecture-based learning (LBL) teaching models on students' learning in surgical education. METHODS: We systematically searched the publications related to the application of PBL and LBL in surgical courses in PubMed, Embase, Web of Science and Cochrane Library databases, the last retrieval time is September 20, 2022. After screening the literature according to the inclusion and exclusion criteria, extracting data and evaluating the methodological treatment of the included studies, Stata 17.0 software was used to perform meta-analysis. RESULTS: Nine studies were included totally. The results showed that compared with LBL, PBL was superior in clinical competence (SMD = 0.81, 95% CI: 0.12 ~ 1.49, P = 0.020) and student satisfaction (SMD = 2.13, 95% CI: 1.11 ~ 3.15, P < 0.0001) with significant differences. But the comprehensive scores (SMD = 0.26, 95% CI: -0.37 ~ 0.89, P = 0.421) and theoretical knowledge (SMD=-0.19, 95% CI: -0.71 ~ 0.33, P = 0.482) to PBL and LBL had no significant difference. CONCLUSION: This study showed that the PBL teaching model is more effective than the LBL teaching model in surgical education on the aspects of enhancing clinical competence and student satisfaction. However, further well-designed studies are needed to confirm our findings.

Are "additional cuts" effective for positive margins in cervical conization? It varies according to the doctor.

BACKGROUND: High-grade squamous intraepithelial lesion (HSIL) is a disease that is closely related to the development of cervical cancer. In clinical work, cold knife conization and a loop electrosurgical excision procedure (LEEP) are often selected for diagnosis and treatment. OBJECTIVE: In this paper, we aimed to discuss additional cuts, a common practice in cervical conization, and determine whether the doctor's choice to use additional cuts in conization can reduce the occurrence of a positive cone margin. METHODS: From January 2018 to October 2019, 965 patients underwent cervical conization at the First Affiliated Hospital of Dalian Medical University (Dalian, China). Of these, 174 were in the positive cone margin group, and 791 were in the negative cone margin group. Age, preoperative pathology, pathological results of conization, additional cuts, cone depth, and cone volume were studied. Additionally, the additional cut rate and the efficiency of doctors with a habit of additional cuts were analyzed. RESULTS: Of the 965 patients included in the study, the median age was 41 years (range 35-50). Multivariable logistic regression analysis suggested that additional cuts (OR, 2.480; 95% CI 1.608 to 3.826; p = 0.01) and smaller cone depth (OR, 0.591; 95% CI, 0.362 to 0.965, p = 0.036) were independent risk factors for positive margins. Six of the 64 doctors who performed conizations had a habit of making additional cuts, and there was no positive correlation between their additional cut rate and their effective additional cut rate. CONCLUSION: This study showed that a certain proportion of additional cuts can be effectively excised from the positive margin that cannot be removed in the initial conization. The practice of additional cuts in conization tends to be the personal habit of a small number of doctors.

Pan-cancer analysis and experimental validation revealed the m6A methyltransferase KIAA1429 as a potential biomarker for diagnosis, prognosis, and immunotherapy.

BACKGROUND: KIAA1429, also known as VIRMA (vir-like m6A methyltransferase associated), plays a crucial role in tumorigenesis by modulating the level of m6A methylation. Previous studies have reported the prevalent overexpression of KIAA1429 in multiple cancers, related to a poor prognosis. Nevertheless, the precise role of KIAA1429 in tumor progression and its impact on the immune response remains unclear. METHODS: A differential analysis of KIAA1429 expression was performed across cancers using data from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. We evaluated the role of KIAA1429 in the diagnosis, prognosis, and immunotherapy of tumor patients using bioinformatics methods. In addition, we also analyzed the associations between KIAA1429 and DNA methylation, immunotherapy. RT-qPCR was used to study the expression levels of KIAA1429 mRNA in 11 cell lines. RESULTS: KIAA1429 is found to be overexpressed in 28 cancer types, but its expression is relatively low in patients with acute myeloid leukemia (LAML) and ovarian serous cystadenocarcinoma (OV). Moreover, KIAA1429 demonstrates a positive correlation with advanced stages of multiple cancers. Kaplan-Meier (KM) analysis suggested that patients with elevated KIAA1429 expression had shorter survival. Furthermore, KIAA1429 shows strong associations with DNA methylation, tumor-infiltrating immune cells (TIICs), and the tumor microenvironment (TME). RT-qPCR results indicated significantly higher expression of KIAA1429 in tumor cells compared to matched-normal cells. CONCLUSIONS: In summary, our work illustrates that KIAA1429 expression is positively connected with poor prognosis in multiple cancers. Moreover, KIAA1429 could serve as a diagnostic factor and a predictor of immune response for specific tumor types.

Mucin 1 expression correlation with lymph node metastasis and micrometastasis and poor prognosis in patients with esophageal squamous cell carcinomas.

Introduction: Lymph node metastasis (LNM) and lymph node micrometastasis (LNMM) are prognostic factors in esophageal squamous cell carcinoma (ESCC) patients. The purpose of this research is to investigate whether mucin 1 expression detected by immunohistochemistry in lymph nodes correlates with LNM, LNMM and prognosis in ESCC patients. Material and methods: There were 92 ESCC patients enrolled in the research, and 1382 lymph nodes were obtained from these 92 patients. All lymph nodes were immunohistochemically analyzed using an anticytokeratin and mucin 1 antibody cocktail. Results: In the pN1-2 patients' group, 68 lymph nodes from 15 patients had tumor metastasis. All these 68 tumor metastatic lymph nodes were positive for mucin 1. Mucin 1 was detected in another 231 lymph nodes and among them, 3 (3/231 1.3%) lymph nodes from 2 (2/15 13.3%) patients were positive for mucin 1. In 77 pN0 patients, mucin 1 was detected in 1083 lymph nodes from the 77 patients; 17 (17/1083 1.6%) lymph nodes from 15 (15/77 19.5%) patients were positive for mucin 1. The 5-year survival rate was 39.1%, and it was significantly related to tumor invasion (pT, p < 0.05), lymph node metastasis (pN, p < 0.01), pTNM stage (p < 0.01) and mucin 1 expression (p < 0.01). Cox regression of multivariate analysis demonstrated that mucin 1 expression and pT were independent prognostic factors. Conclusions: Mucin 1 expression was related to LNM and LNMM and poor prognosis in ESCC patients. Immunohistochemistry for mucin 1 can be applied for the detection of LNM and LNMM.

Association between CD8+ tumor-infiltrating lymphocytes and prognosis of non-small cell lung cancer patients treated with PD-1/PD-L1 inhibitors: a systematic review and meta-analysis.

BACKGROUND: A meta-analysis method was used to investigate the prognostic value of CD8+ tumor-infiltrating lymphocytes (TILs) in non-small cell lung cancer (NSCLC) patients treated with PD-1/PD-L1 inhibitors. METHODS: A database search of PubMed, Embase, Web of Science and Cochrane Library up until 7 February, 2023. A clinical study on the relationship between CD8+ TILs and PD-1/PD-L1 inhibitors in the therapeutics of NSCLC. RevMan 5.3 and StataMP 17.0 software were used for meta-analysis. The outcome indicators incorporated overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). RESULTS: Nineteen articles with 1488 patients were included. The analysis results showed that high CD8+ TILs were associated with better OS (HR = 0.60, 95% CI: 0.46-0.77; P < 0.0001), PFS (HR = 0.68, 95% CI: 0.53-0.88; P = 0.003) and ORR (OR = 2.26, 95% CI: 1.52-3.36; P < 0.0001) in NSCLC patients treated with PD-1/PD-L1 inhibitors. Subgroup analysis indicated that patients with high CD8+ TILs had good clinical prognostic benefits whether the location of CD8+ TILs was intratumoral or stromal, and compared with East Asian, high CD8+ TILs in Caucasians showed a better prognosis. High CD8+ TILs in peripheral blood did not improve OS (HR = 0.83, 95% CI: 0.69-1.01; P = 0.06) and PFS (HR = 0.93, 95% CI: 0.61-1.14; P = 0.76) in NSCLC patients receiving PD-1/PD-L1 inhibitors. CONCLUSION: In spite of the location of CD8+ TILs, high densities of CD8+ TILs were predictive of treatment outcomes in NSCLC patients treated with PD-1/PD-L1 inhibitors. However, high CD8+ TILs in peripheral blood had no predictive effect.

Targeting neddylation as a novel approach to lung cancer treatment (Review).

As a protein that resembles ubiquitin, neural precursor cell expressed developmentally downregulated 8 (NEDD8) takes part in neddylation, which modifies substrates in a manner similar to ubiquitination and alters the activity of target proteins. Neddylation may affect the activity of multiple signaling pathways, have a regulatory role in tumor formation, progression and metastasis, and influence the prognosis of cancer treatment. The present review summarizes the regulatory roles of NEDD8 in the MDM2­p53, NF­κB, PI3K/AKT/mTOR, hypoxia­inducible factor, Hippo and receptor tyrosine kinase signaling pathways, as well as in the development and progression of lung cancer.

Single-cell profiling of the copy-number heterogeneity in colorectal cancer.

BACKGROUND: With functionally heterogeneous cells, tumors comprise a complex ecosystem to promote tumor adaptability and evolution under strong selective pressure from the given microenvironment. Diversifying tumor cells or intra-tumor heterogeneity is essential for tumor growth, invasion, and immune evasion. However, no reliable method to classify tumor cell subtypes is yet available. In this study, we introduced the single-cell sequencing combined with copy number characteristics to identify the types of tumor cells in microsatellite stable (MSS) colorectal cancer (CRC). METHODS: To characterize the somatic copy number alteration (SCNA) of MSS CRC in a single cell profile, we analyzed 26 tissue samples from 19 Korean patients (GSE132465, the Samsung Medical Center [SMC] dataset) and then verified our findings with 15 tissue samples from five Belgian patients (GSE144735, the Katholieke Universiteit Leuven 3 [KUL3] dataset). The Cancer Genome Atlas (TCGA) cohort, GSE39582 cohort, and National Cancer Center (NCC) cohort (24 MSS CRC patients were enrolled in this study between March 2017 and October 2017) were used to validate the clinical features of prognostic signatures. RESULTS: We employed single cell RNA-sequencing data to identify three types of tumor cells in MSS CRC by their SCNA characteristics. Among these three types of tumor cells, C1 and C3 had a higher SCNA burden; C1 had significant chromosome 13 and 20 amplification, whereas C3 was the polar opposite of C1, which exhibited deletion in chromosome 13 and 20. The three types of tumor cells exhibited various functions in the tumor microenvironment and harbored different mutations. C1 and C2 were linked to the immune response and hypoxia, respectively, while C3 was critical for cell adhesion activity and tumor angiogenesis. Additionally, one gene ( OLFM4 ) was identified as epithelium-specific biomarker of better prognosis of CRC (TCGA cohort: P  = 0.0110; GSE39582 cohort: P  = 0.0098; NCC cohort: P  = 0.0360). CONCLUSIONS: On the basis of copy number characteristics, we illustrated tumor heterogeneity in MSS CRC and identified three types of tumor cells with distinct roles in tumor microenvironment. By understanding heterogeneity in the intricate tumor microenvironment, we gained an insight into the mechanisms of tumor evolution, which may support the development of therapeutic strategies.

Activity-Based Imaging of Macrophage Migration Inhibitory Factor with a Two-Photon Fluorescent Probe.

Macrophage migration inhibitory factor (MIF), as a cytokine, plays an important role in the pathogenesis of cancer and some other diseases, and it is also one of the potential drug targets for disease treatment. However, due to the lack of simple and effective MIF imaging detection tools, the fluctuation and distribution of MIF in living cells or at lesion sites remain difficult to track precisely and in real time. Here, we report activity-based fluorescent probes, named MIFP1-MIFP3, which are used for real-time imaging and tracking of intracellular MIF, thus establishing a relationship between the fluctuation of MIF and the change of fluorescence signal during the cancer disease process. With the excellent optical properties of two-photon probe imaging, we can easily distinguish multiple cancer cells from normal cells with the representative probe, MIFP3. Moreover, MIFP3 has also been successfully used to directly identify the pathological tissues of patients with clinical liver cancer. These potential MIF probes could provide powerful tools for further study of the physiological function of MIF and will be helpful to promote the accurate diagnosis and therapeutic evaluation of MIF-associated malignancies.

Clinical and prognostic features of E-cadherin in adenocarcinoma of the esophagogastric junction patients.

OBJECTIVE: The expression, activity, and functional role of E-cadherin in adenocarcinoma of the esophagogastric junction (AEG) are unclear. In this research, we evaluated the expression of E-cadherin in AEG, as well as its clinicopathological significance and prognostic value. METHODS: A total of 65 AEG samples and 10 normal paracancerous tissues undergoing AEG resection in thoracic surgery were collected. The samples were immunohistochemically examined for expression levels of E-cadherin. The Chi-square test was used to determine if E-cadherin expression correlated with the clinicopathological features of AEG patients. The link between clinicopathological features and 5-year survival rates was investigated using Kaplan-Meier survival curves and multifactorial Cox regression analysis. RESULTS: In AEG tissues, E-cadherin expression was considerably reduced. Differentiation grade ( P = 0.013), infiltration depth ( P = 0.033), and clinicopathological stage ( P = 0.045) were substantially linked to the level of E-cadherin expression. Five-year survival rates of AEG patients were affected by E-cadherin expression ( P = 0.037), tumor differentiation ( P = 0.010), lymph node metastasis ( P < 0.001), and clinicopathological stage ( P = 0.037). Tumor differentiation ( P = 0.033) and lymph node metastasis ( P = 0.001) were independent risk factors for shorter overall survival. CONCLUSION: E-cadherin expression in AEG was significantly decreased, which was strongly related to tumor differentiation, infiltration, and clinicopathological stage. An E-cadherin deficiency would lead to poor prognosis in AEG patients. E-cadherin may play a crucial role in AEG invasion and metastasis. Low expression of E-cadherin may be a potential early biomarker and overall survival predictor for AEG patients.

Roles of Krüppel-like factor 6 splice variant 1 in the development, diagnosis, and possible treatment strategies for non-small cell lung cancer.

Krüppel-like factor 6 (KLF6) is a nuclear transcriptional regulator found in mammalian tissue that has been identified as a tumor suppressor gene in several malignancies. As a result of loss of heterozygosity, DNA methylation, and alternative splicing, it is frequently inactivated in various malignancies. Krüppel-like factor 6 splice variant 1 (KLF6-SV1), Krüppel-like factor 6 splice variant 2, and Krüppel-like factor 6 splice variant 3 alternatively spliced isoforms that emerge from a single nucleotide polymorphism in the KLF6 gene. KLF6-SV1 is generally upregulated in multiple cancers, and its biological function is well understood. Overexpression of KLF6-SV1 inhibits the KLF6 gene function while promoting tumor progression, which is associated with a poor prognosis in patients with various malignancies. We reviewed the progress of KLF6-SV1 research in NSCLC over the last several years to understand the molecular mechanisms of tumorigenesis, tumor development, and therapy resistance. Finally, this review emphasizes the therapeutic potential of small interfering RNA targeted silencing of KLF6-SV1 as a novel strategy for managing chemotherapy resistance in NSCLC patients.