Effect of the STK11 mutation on therapeutic efficacy and prognosis in patients with non-small cell lung cancer: a comprehensive study based on meta-analyses and bioinformatics analyses.

BACKGROUND: This study aimed to systematically analyze the effect of a serine/threonine kinase (STK11) mutation (STK11mut) on therapeutic efficacy and prognosis in patients with non-small cell lung cancer (NSCLC). METHODS: Candidate articles were identified through a search of relevant literature published on or before April 1, 2023, in PubMed, Embase, Cochrane Library, CNKI and Wanfang databases. The extracted and analyzed data included the hazard ratios (HRs) of PFS and OS, the objective response rate (ORR) of immune checkpoint inhibitors (ICIs), and the positive rates of PD-L1 expression. The HR of PFS and OS and the merged ratios were calculated using a meta-analysis. The correlation between STK11mut and clinical characteristics was further analyzed in NSCLC datasets from public databases. RESULTS: Fourteen retrospective studies including 4317 patients with NSCLC of whom 605 had STK11mut were included. The meta-analysis revealed that the ORR of ICIs in patients with STK11mut was 10.1% (95%CI 0.9-25.2), and the positive rate of PD-L1 expression was 41.1% (95%CI 25.3-57.0). STK11mut was associated with poor PFS (HR = 1.49, 95%CI 1.28-1.74) and poor OS (HR = 1.44, 95%CI 1.24-1.67). In the bioinformatics analysis, PFS and OS in patients with STK11 alterations were worse than those in patients without alterations (p < 0.001, p = 0.002). Nutlin-3a, 5-fluorouracil, and vinorelbine may have better sensitivity in patients with STK11mut than in those with STK11wt. CONCLUSIONS: Patients with STK11-mutant NSCLC had low PD-L1 expression and ORR to ICIs, and their PFS and OS were worse than patients with STK11wt after comprehensive treatment. In the future, more reasonable systematic treatments should be explored for this subgroup of patients with STK11-mutant NSCLC.

Diagnostic value of methylated branched chain amino acid transaminase 1/IKAROS family zinc finger 1 for colorectal cancer.

BACKGROUND: The diagnostic value of combined methylated branched chain amino acid transaminase 1 (BCAT1)/IKAROS family zinc finger 1 (IKZF1) in plasma for colorectal cancer (CRC) has been explored since 2015. Recently, several related studies have published their results and showed its diagnostic efficacy. AIM: To analyze the diagnostic value of methylated BCAT1/IKZF1 in plasma for screening and postoperative follow-up of CRC. METHODS: The candidate studies were identified by searching the PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases from May 31, 2003 to June 1, 2023. Sensitivity, specificity, and diagnostic accuracy were calculated by merging ratios or means. RESULTS: Twelve eligible studies were included in the analysis, involving 6561 participants. The sensitivity of methylated BCAT1/IKZF1 in plasma for CRC diagnosis was 60% [95% confidence interval (CI) 53-67] and specificity was 92% (95%CI: 90-94). The positive and negative likelihood ratios were 8.0 (95%CI: 5.8-11.0) and 0.43 (95%CI: 0.36-0.52), respectively. Diagnostic odds ratio was 19 (95%CI: 11-30) and area under the curve was 0.88 (95%CI: 0.85-0.91). The sensitivity and specificity for CRC screening were 64% (95%CI: 59-69) and 92% (95%CI: 91-93), respectively. The sensitivity and specificity for recurrence detection during follow-up were 54% (95%CI: 42-67) and 93% (95%CI: 88-96), respectively. CONCLUSION: The detection of methylated BCAT1/IKZF1 in plasma, as a non-invasive detection method of circulating tumor DNA, has potential CRC diagnosis, but the clinical application prospect needs to be further explored.

Efficacy and toxicity of drugs targeting KRASG12C mutation in non-small cell lung cancer: a meta-analysis.

OBJECTIVE: To systematically analyze the efficacy and toxicity of drugs targeting KRASG12C mutation in non-small cell lung cancer (NSCLC). METHODS: The candidate studies were identified in PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases up to 1 June 2023. Data on efficacy, prognosis, and adverse events (AEs) were extracted and calculated by meta-analysis. RESULTS: Six eligible prospective studies were included in this meta-analysis, including 563 patients with advanced or metastatic NSCLC. For patients with NSCLC, the objective response rate (ORR) of drugs targeting KRASG12C mutation was 37% (95%CI 31-43), median duration of response (DOR) was 8.89 months (95%CI 7.96-9.83), and median progression-free survival (PFS) was 6.40 months (95%CI 5.86-6.93). The overall incidence of AEs was 88% (95%CI 79-96) and the incidence of grade ≥3 AEs was 44% (95%CI 24-64). The most common AEs were diarrhea, nausea, fatigue, and vomiting. The most common grade ≥3 AEs were Alaninetransaminase (ALT) or Aspartatetransaminase (AST) increased and diarrhea. CONCLUSION: Sotorasib, Adagrasib, and Garsorasib as the drugs of choice for patients with KRASG12C mutation NSCLC, have definite efficacy and acceptable safety, especially for patients with advanced or metastatic disease and within posterior line therapy.