The proliferation marker Ki67 has prognostic and predictive values in breast cancer, and the cutoff of the Ki67 label index (LI) is a key index for chemotherapy. However, poor interobserver consistency in Ki67 assessment has limited the clinical use of Ki67, especially in luminal cancers. Here, we reported a modified Ki67 assessment method, size-set semiautomatic counting (SSSAC) and investigated its interobserver reproducibility. One hundred invasive breast cancer tissues were set immunostained for Ki67 in one laboratory, scanned as digital slides, and sent to 41 pathologists at the laboratories of 16 hospitals for Ki67 LI assessment using size-set semiautomatic counting (SSSAC), size-set visual assessment (SSVA) and size-set digital image analysis (SSDIA) with a specific image viewing software (Aperio Image Scope, Leica, Germany). The intraclass correlation coefficient (ICC) and Bland-Altman plot were used to evaluate interobserver reproducibility. The Wilcoxon signed-rank test was used to analyze the difference in the Ki67 values assessed by SSSAC and SSDIA. SSSAC demonstrated better interobserver reproducibility (ICC = 0.942) than SSVA (ICC = 0.802). The interobserver reproducibility was better in Ki67 homogeneously stained slides and centralized hot-spot slides than in scattered hot-spot slides. The Ki67 value assessed with SSSAC was obviously higher than that assessed with SSDIA (negative ranks (SSDIA < SSSAC): N = 80, sum of ranks = 4274.50; positive ranks (SSDIA > SSSAC): N = 17, sum of ranks = 478.50; Z = -6.837; P < 0.001). SSSAC shows satisfactory interobserver reproducibility in the Ki67 assessment of breast cancer and may be a candidate standard method for Ki67 LI assessment in breast cancer and other malignancies.

Long noncoding RNAs (lncRNAs) have emerged as critical regulators of tumor progression, and lncRNA expression levels could serve as a potential molecular biomarker for the prognosis and diagnosis of some cancers. However, the prognostic value of lncRNAs in oral squamous cell carcinoma (OSCC) remains unclear. Thus, a meta-analysis was conducted to explore the potential prognostic value of lncRNAs in OSCC. We systematically searched PubMed, EBSCO, Web of Science, and Elsevier from 2005 to 2021 to identify all published studies that reported the association between lncRNAs and prognosis in OSCC. Then, we used meta-analytic methods to identify the actual effect size of lncRNAs on cancer prognosis. The hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated to assess the strength of the association. The reliability of those results was then examined using measures of heterogeneity and testing for selective reporting biases. According to the inclusion and exclusion criteria, a total of 17 studies were eligible in our meta-analysis, involving 1384 Asian patients. The results identified a statistically significant association of high lncRNA expression with poor overall survival [adjusted pooled hazard ratio ; 95% confidence interval (CI): [1.26–1.84], ]. The present meta-analysis demonstrated that lncRNA expression might be used as a predictive prognostic biomarker for Asian patients with OSCC.

No targeted therapies are approved for non-small-cell lung cancer (NSCLC) with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation to date. Trametinib, a selective allosteric inhibitor of the MEK1/2, demonstrated debatable clinical activity in KRAS-mutant NSCLC. In this case, we present a recurrent advanced NSCLC with KRAS G12C mutation successfully treated with single-agent trametinib therapy. An 87-year-old man who underwent radiotherapy for the right lung adenocarcinoma was admitted to clinical oncology center for recurrent lesions in bilateral lungs. He was unwilling to perform second-line chemotherapy, but underwent molecular profiling and revealed the KRAS G12C mutation. The single-agent target therapy of trametinib showed clinical benefit without obvious toxicity. Furthermore, this report reviewed the previous date of the preclinical and clinical and summarized that KRAS G12C mutation may be more sensitive to the inhibition of mitogen-activated protein kinase kinase. This case advocates for routine screening of KRAS point mutations in the utility of precision medicine and suggests that treatment with trametinib in advanced NSCLC cases with KRAS G12C mutation is well tolerated and effective, especially for those very elderly or unsuitable for more aggressive chemotherapy.

The regulatory ability of bone marrow stem cells (BMSC) to chemokines and inflammatory factors has a significant effect in a variety of diseases. It is very important to delay the aging of BMSC and restore the function of aging BMSC. Mouse BMSC was prepared and identified. TCAB1 gene interference (Sh-TCAB1), interference control (Sh-NC), overexpression (OE-TCAB1) and overexpression control (OE-NC) stable cell lines of BMSC were established, and the relationship between TCAB1 expression and senescence of BMSC cells was analyzed. Transcriptome high-throughput sequencing was performed to further analyze the mechanism of TCAB1 in BMSC aging. The phenotype of BMSC was normal by flow cytometry, and the cultured cells were identified as BMSC by osteogenic lipogenic differentiation staining. The fluorescence transfection efficiency of TCAB1-interfered and overexpressed stable strain was 90%, and the stable strain of interfered and overexpressed TCAB1 gene was successfully constructed. Overexpression of TCAB1 inhibits BMSC senescence, and TCAB1 interferes with and accelerates BMSC senescence. Transcriptome sequencing results show that TCAB1 can regulate signaling pathways related to BMSC metabolism and cell cycle to play an anti-BMSC senescence role. Transcriptome sequencing suggests that the mechanism of TCAB1 inhibiting BMSC senescence is related to cell cycle and metabolic process, and exerts anti-BMSC senescence function by regulating the expression of key factors Slc2a1 and Egln3. This study confirmed that the expression of TCAB1 is closely related to the senescence of BMSC through molecular level, which provides a new technique for the clinical treatment of cell senescence.

Background: Ovarian ageing refers to the progressive functional decline and structural degeneration of the ovary with advancing age, primarily manifested as a reduction in both the quantity and quality of follicles. These changes lead to decreased female fertility, increased miscarriage rates, and elevated risks of age-related diseases. Current treatments cannot fundamentally promote ovarian regeneration. Mesenchymal stem cells (MSCs) possess properties such as self-renewal and paracrine signalling, and their transplantation can restore ovarian function, with the paracrine pathway being a key mechanism. Insulin-like growth factor 1 (IGF-1), a peptide growth factor secreted by MSCs, regulates ovarian cell proliferation, differentiation, and survival through pathways like PI3K/Akt and Ras/Raf/MEK/ERK. Objective: To summarize and critically evaluate the latest research progress on the role of MSC-secreted IGF-1 in restoring ovarian function. Conclusion: IGF-1 is an important mediator through which MSCs ameliorate ovarian ageing, improving ovarian tissue structure, hormone secretion, and fertility in preclinical models. However, most evidence remains preclinical, and future work should address the translational challenges, including safety, efficacy, and the precise role of IGF-1 within the complex MSCs paracrine network.