Tissue Microarray Analysis Reveals Heterogeneous Expression of Talin-1 and Lactate Dehydrogenase A in Non-small Cell Lung Cancer: Implications for Biomarker Reliability

Background Tumour heterogeneity significantly impacts biomarker reliability in non-small cell lung cancer (NSCLC), such as lactate dehydrogenase A (LDHA) and Talin-1, thus complicating the validation of their diagnostic utility. This study investigated their expression heterogeneity in tissue microarrays (TMAs) from 40 non-metastatic NSCLC cases (24 squamous cell carcinomas, 16 adenocarcinomas) and 10 normal lung tissues, using standardised immunohistochemistry. Methodology Formalin-fixed, paraffin-embedded TMAs were stained with anti-LDHA and anti-Talin-1 antibodies. Cores were clustered based on their expression intensity, scored from 0 to 3 for intensity, and analysed against tumour grade/stage. A two-sided Pearson chi-square test was used to calculate the significance between normal and cancer tissue expression and to correlate the expression with the tumour grade/stage. Fisher’s exact test was also considered when nodule counts were less than five. Results LDHA expression was significantly higher in adenocarcinoma (χ² = 20.30, p < 0.001) and squamous cell carcinoma (χ² = 28.34, p < 0.001) compared with normal lung tissue, with a heterogeneous expression pattern, although no association was observed with tumour stage, grade, or lymph node status. These findings suggest that its expression heterogeneity may contribute to the inconsistency in its reported diagnostic utility across studies for lung cancer diagnosis, highlighting the need for multiplexed biomarker panels to overcome limitations driven by heterogeneity. In contrast, Talin-1 expression was reduced in malignancy and did not demonstrate statistical significance in adenocarcinoma (χ² = 2.11, p = 0.146), squamous cell carcinoma (χ² = 0.01, p = 0.912), or NSCLC overall (χ² = 1.12, p = 0.289). Talin-1 expression also had a heterogeneous pattern with no correlation with the tumour clinicopathological parameters. Conclusions Our findings revealed significant heterogeneity in LDHA and Talin-1 expression across NSCLC subtypes, independent of tumour grade and stage. This observed variability supports the need for using multiplexed panels and patient-based rather than single-marker approaches for reliable clinical applications.