The detection of serum biomarkers can aid in the diagnosis of lung cancer. In recent years, an increasing number of lung cancer markers have been identified, and these markers have been reported to have varying diagnostic values. A method to compare the diagnostic value of different combinations of biomarkers needs to be established to identify the best combination. In this study, automatic chemiluminescence analyzers were employed to detect the serum concentrations of carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), cytokeratin 19 fragment (CY211), neuron-specific enolase (NSE), and squamous cell carcinoma antigen (SCC) in 780 healthy subjects, 650 patients with pneumonia, and 633 patients with lung cancer. Receiver operating characteristic (ROC) curve and logistic regression analyses were also used to evaluate the diagnostic value of single and multiple markers of lung cancer. The sensitivities of the five markers alone were lower than 65% for lung cancer screening in healthy subjects and pneumonia patients. SCC was of little value in screening lung cancer. After combining two or more markers, the areas under the curves (AUCs) did not increase with the increase in the number of markers. For healthy subjects, the best marker for lung cancer screening was the combination CEA + CA125, and the positive cutoff range was 0.577 CEA + 0.035 CA125 > 2.084. Additionally, for patients with pneumonia, the best screening markers displayed differences in terms of sex but not age. The best screening marker for male patients with pneumonia was the combination CEA + CY211 with a positive cutoff range of 0.008 CEA + 0.068 CY211 > 0.237, while that for female patients with pneumonia was CEA > 2.73 ng/mL, which could be regarded as positive. These results showed that a two-marker combination is more suitable than a multimarker combination for the serological screening of tumors. Combined ROC curve and logistic regression analyses are effective for identifying the best markers for lung cancer screening.

1037 Background: A166, an antibody-drug conjugate, with an anti-HER2 antibody site-specifically conjugated to Duo-5 (anti-microtubule agent), via a stable protease-cleavable valine citrulline linker, has proved its safety and efficacy in patients with HER2 positive breast cancer (Xichun Hu et al. ASCO 2021). Here, we report updated data and biomarker analyses from this single-arm, multi-center, open-label, phase I trial (CTR20181301). Methods: This study has two parts: dose escalation and dose expansion. In the expansion part, dose cohorts were expanded at 4.8 and 6.0 mg/kg Q3W, and the primary endpoint was ORR, as assessed according to the RECIST 1.1. Next-generation sequencing was performed on tissue-derived DNA and blood-derived circulating tumor DNA (ctDNA). Results: As of Dec 10, 2021, in total 58 female pts were enrolled in the expansion dose cohorts. Median age was 53.5 years (range 26-71), 58 pts (100%) had prior HER2-targeted therapy with the median lines of 4, including 100% received trastuzumab ± pertuzumab, 94.8% received anti-HER2 TKIs, and 20.7% received anti-HER2 ADCs in the metastatic setting. Any grade treatment-related AEs (TRAEs) were documented in 100.0% (58/58) of pts. Common TRAEs were corneal epitheliopathy (98.3%), blurred vision (89.7%), peripheral sensory neuropathy (67.2%), muscular weakness (36.2%) and dry eyes (32.8%). Most common grade ≥3 TRAEs were corneal epitheliopathy (34.5%), blurred vision (22.4%) and ulcerative keratitis (10.3%). 7 pts had serious AEs, 3 of whom were possibly related to the study drug, including thrombosis, peripheral motor neuropathy and muscular weakness. TRAEs led to 39.7% (23/58) dose reduction and 1.7% (1/58) treatment discontinuation. All patients were evaluable for efficacy with the best ORR being 73.91% (17/23; 95% CI, 51.59 to 89.77) and 68.57% (24/35; 95% CI, 50.71 to 83.15), mPFS being 12.30 months (95% CI, 6.00 to not reached) and 9.40 months (95% CI, 4.00 to 10.40) in 4.8 and 6.0 mg/kg cohort, respectively. Of 23 pts treated at 4.8 mg/kg dose level, one had a confirmed and sustained complete response lasting 7+ months. At the time of the data cutoff, 24 pts (41.4%) continued to receive A166 treatment.NGS of 520 genes was performed on tissue-derived DNA and ctDNA of baseline tumor tissue samples (n = 42) and blood samples (n = 53), respectively, and post-treatment blood samples (n = 8). Univariate and multivariate analysis showed that baseline PIK3CA/PTEN status had no influence on the PFS, and gave an idea of FGFR1 amplification as a potential negative predictor of A166 efficacy in HER2-positive breast cancer. Conclusions: The previously demonstrated preliminary clinical benefit of A166-ADC was maintained with no new safety signals, which demonstrated manageable toxicity and encouraging anti-tumor activity in heavily pretreated HER2-positive metastatic breast cancer patients. Clinical trial information: CTR20181301.

Esophageal cancer (EC) is an extremely aggressive malignant tumor. Homeobox A10 (HOXA10) is highly expressed and plays an important role in a variety of tumors. However, the function of HOXA10 in EC remains unclear. In this study, HOXA10 was observed to highly express in EC tissues and cells. Interestingly, the CCK-8 assay, flow cytometry, and colony formation assay confirmed that overexpression of HOXA10 promoted proliferation and suppressed cell apoptosis in EC cells. More importantly, the western blot assay indicated that the phosphorylation levels of ERK and p38 were elevated in EC cells overexpressed HOXA10, indicating that overexpression of HOXA10 activated p38/ERK signaling pathway in EC cells. These findings concluded that HOXA10 aggravated EC progression via activating p38/ERK signaling pathway, providing a potential therapeutic target for EC.