Gastric cancer (GC) is a malignancy with high morbidity/mortality, partly due to a lack of reliable biomarkers for early diagnosis. It is important to develop reliable biomarker(s) with specificity, sensitivity and convenience for early diagnosis. The role of tumour-associated macrophages (TAMs) and survival of GC patients are controversial. Macrophage colony stimulating factor (MCSF) regulates monocytes/macrophages. Elevated MCSF is correlated with invasion, metastasis and poor survival of tumour patients. IL-34, a ligand of the M-CSF receptor, acts as a “twin” to M-CSF, demonstrating overlapping and complimentary actions. IL-34 involvement in tumours is controversial, possibly due to the levels of M-CSF receptors. While the IL-34/M-CSF/M-CSFR axis is very important for regulating macrophage differentiation, the specific interplay between these cytokines, macrophages and tumour development is unclear. A multi-factorial evaluation could provide more objective utility, particularly for either prediction and/or prognosis of gastric cancer. Precision medicine requires molecular diagnosis to determine the specifically mutant function of tumours, and is becoming popular in the treatment of malignancy. Therefore, elucidating specific molecular signalling pathways in specific cancers facilitates the success of a precision medicine approach. Gastric cancer tissue arrays were generated from stomach samples with TNM stage, invasion depth and the demography of these patients (n = 185). Using immunohistochemistry/histopathology, M-CSF, IL-34 and macrophages were determined. We found that IL-34 may serve as a predictive biomarker, but not as an independent, prognostic factor in GC; M-CSF inversely correlated with survival of GC in TNM III–IV subtypes. Increased CD68+ TAMs were a good prognostic factor in some cases and could be used as an independent prognostic factor in male T3 stage GC. Our data support the potency of IL-34, M-CSF, TAMs and the combination of IL-34/TAMs as novel biological markers for GC, and may provide new insight for both diagnosis and cellular therapy of GC.

中文翻译：

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Interleukin-34 与胃癌之间的负相关，胃癌是一种潜在的预后生物标志物。

胃癌 (GC) 是一种具有高发病率/死亡率的恶性肿瘤，部分原因是缺乏用于早期诊断的可靠生物标志物。开发具有特异性、敏感性和便利性的可靠生物标志物对早期诊断非常重要。肿瘤相关巨噬细胞 (TAM) 的作用和 GC 患者的存活率是有争议的。巨噬细胞集落刺激因子 (MCSF) 调节单核细胞/巨噬细胞。升高的 MCSF 与肿瘤患者的侵袭、转移和较差的生存率相关。IL-34 是 M-CSF 受体的配体，作为 M-CSF 的“双胞胎”，表现出重叠和互补作用。IL-34 参与肿瘤是有争议的，可能是由于 M-CSF 受体的水平。虽然 IL-34/M-CSF/M-CSFR 轴对于调节巨噬细胞分化非常重要，这些细胞因子、巨噬细胞和肿瘤发展之间的具体相互作用尚不清楚。多因素评估可以提供更客观的效用，特别是对于胃癌的预测和/或预后。精准医学需要分子诊断来确定肿瘤的特异性突变功能，并且在恶性肿瘤的治疗中越来越流行。因此，阐明特定癌症中的特定分子信号通路有助于精准医学方法的成功。胃癌组织阵列是从具有 TNM 分期、侵袭深度和这些患者 (n = 185) 的人口统计学的胃样本中生成的。使用免疫组织化学/组织病理学，测定 M-CSF、IL-34 和巨噬细胞。我们发现 IL-34 可以作为预测性生物标志物，但不是独立的，GC中的预后因素；在 TNM III-IV 亚型中，M-CSF 与 GC 的存活率呈负相关。在某些情况下，增加的 CD68+ TAM 是一个很好的预后因素，可用作男性 T3 期 GC 的独立预后因素。我们的数据支持 IL-34、M-CSF、TAM 和 IL-34/TAM 组合作为 GC 新生物标志物的效力，并可能为 GC 的诊断和细胞治疗提供新的见解。