Targeting KRASG12D mutation in non-small cell lung cancer: molecular mechanisms and therapeutic potential.

Lung malignant tumors are a type of cancer with high incidence and mortality rates worldwide. Non-small cell lung cancer (NSCLC) accounts for over 80% of all lung malignant tumors, and most patients are diagnosed at advanced stages, leading to poor prognosis. Over the past decades, various oncogenic driver alterations associated with lung cancer have been identified, each of which can potentially serve as a therapeutic target. Rat sarcoma (RAS) genes are the most commonly mutated oncogenes in human cancers, with Kirsten rat sarcoma (KRAS) being the most common subtype. The role of KRAS oncogene in NSCLC is still not fully understood, and its impact on prognosis remains controversial. Despite the significant advancements in targeted therapy and immune checkpoint inhibitors (ICI) that have transformed the treatment landscape of advanced NSCLC in recent years, targeting KRAS (both directly and indirectly) remains challenging and is still under intensive research. In recent years, significant progress has been made in the development of targeted drugs targeting the NSCLC KRASG12C mutant subtype. However, research progress on target drugs for the more common KRASG12D subtype has been slow, and currently, no specific drugs have been approved for clinical use, and many questions remain to be answered, such as the mechanisms of resistance in this subtype of NSCLC, how to better utilize combination strategies with multiple treatment modalities, and whether KRASG12D inhibitors offer substantial efficacy in the treatment of advanced NSCLC patients.

Assessment of safety during hospitalization for patients undergoing Surgery after neoadjuvant therapy for moderately advanced Esophageal cancer.

PURPOSE: To study the safety of patients with moderately advanced esophageal cancer during their hospital stay after undergoing surgery. METHODS: The clinical and pathological data of 66 patients with locally advanced esophageal cancer discharged from the Department of Thoracic Surgery of Jiangsu University Hospital from January 2017 to October 2022 were selected, of whom 32 underwent direct surgery (control group) and 34 underwent neoadjuvant therapy followed by surgery (experimental group), to retrospectively analyze whether there were differences in surgical outcomes, complication rates, biochemical and infection indicators between the two groups. RESULTS: The number of lymph node dissections, lymph node dissection rate, and hemoglobin value on the first day after the operation in the experimental group were smaller than those in the control group, and the difference was statistically significant (P < 0.05). The thoracic drainage volume of the experimental group was more than that of the control group, and the difference was statistically significant (P < 0.05). The incidence of pulmonary complications in the experimental group was higher than that in the control group, especially pulmonary infection, and the difference was statistically significant (P < 0.05). Compared with the control group, the experimental group was more prone to anastomotic leakage, and the difference was statistically significant (P < 0.05). CONCLUSION: Neoadjuvant therapy combined with surgery for patients with advanced esophageal cancer is generally safe during hospitalization.

Bioinformatics analysis of differentially expressed miRNAs in non-small cell lung cancer.

OBJECTIVE: Non-small cell lung cancer (NSCLC) contains 85% of lung cancer. Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the largest NSCLC subgroups. The aim of the study was to investigate the underlying mechanism in developing more effective subtype-specific molecular therapeutic procedures. METHODS: A total of 876 specimens were used in this study: 494 LUAD tissues (ie, 449 LUAD tissues and 45 matched normal tissues) and 382 LUSC tissues (ie, 337 LUSC tissues and 45 matched normal tissues). The miRNA sequencing data were processed using R. The differential expressed miRNAs between lung cancer and normal tissues were analyzed using the limma package in R. Gene expression, Western blotting, hematoxylin and eosin staining, and luciferase assay were used to test LUAD and LUSC. RESULTS: LUAD and LUSC appear sharply distinct at molecular and pathological level. Let-7a-5p, miR-338, miR-375, miR-217, miR-627, miR-140, miR-147b, miR-138-2, miR-584, and miR-197 are top 10 relevant miRNAs and CLDN3, DSG3, KRT17, TMEM125, KRT5, NKX2-1, KRT7, ABCC5, KRAS, and PLCG2 are top 10 relevant genes in NSCLC. At the same time, the miRNAs expression levels were also quite different between the two groups. Among the differential expressed miRNAs, let-7a-5p was significantly down-regulated in LUAD while miR-338 was markedly down-regulated in LUSC. Bioinformatics analyses appeared that let-7a-5p directly targets high-molecular weight keratin 5 (KRT5) which were shown to be a strong risk factor for LUAD. And NK2 homeobox 1(NKX2-1) which was associated with tumor progression in LUSC was identified as a target gene of miR-338. CONCLUSIONS: Distinct profile of miRNAs can take a part in the development of LUAD and LUSC and thus could serve as a subtype-specific molecular therapeutic target to protect against LUAD and LUSC.

LncRNA MAGI2-AS3 Upregulates Cytokine Signaling 1 by Sponging miR-155 in Non-Small Cell Lung Cancer.

Background: MAGI2-AS3 has been reported to be a tumor suppressor in breast cancer and bladder cancer. This study analyzed the role of MAGI2-AS3 in non-small cell lung cancer (NSCLC). Results: The authors found that MAGI2-AS3 and suppressor of cytokine signaling 1 (SOCS-1) were both downregulated in NSCLC. MAGI2-AS3 and SOCS-1 were significantly and positively correlated in NSCLC tumor tissues. During follow-up, low levels of MAGI2-AS3 and SOCS-1 were found to be significantly correlated with patients' poor survival. In NSCLC cells, MAGI2-AS3 overexpression mediated the upregulated, while miR-155 expression mediated the downregulated SOCS-1 overexpression. RNA binding analysis showed that MAGI2-AS3 may be a sponge of miR-155. Cell proliferation revealed decreased cell proliferation rate of NSCLC cells after MAGI2-AS3 and SOCS-1 overexpression. MiR-155 played an opposite role and reduced the effects of MAGI2-AS3 overexpression. Conclusion: Therefore, MAGI2-AS3 upregulates cytokine signaling 1 by sponging miR-155 to inhibit NSCLC cell proliferation.