# Beyond Individual Acute Phase Protein Assessments: Introducing the Acute Phase Index (API) as a Prognostic Indicator in Dogs with Malignant Neoplasia

## TL;DR

This study introduces the Acute Phase Index (API) as a new tool to predict survival in dogs with cancer by combining changes in specific proteins linked to inflammation.

## Contribution

The novel contribution is the application of the Acute Phase Index (API) to assess prognosis in dogs with malignant neoplasia.

## Key findings

- Dogs with an API greater than 0.049 at first sampling had a 3.7-fold higher risk of death.
- Lower Paraoxonase-1 (PON-1) levels were observed in round-cell tumors, suggesting higher oxidative stress.
- Elevated APIs and C-reactive protein levels were associated with shorter survival times in cancer-bearing dogs.

## Abstract

Cancer can alter the levels of acute phase proteins (APPs), which are involved in the innate immune response characterized by high sensitivity and low specificity. Combining APPs into an Acute Phase Index (API) enhanced their utility in monitoring human disease progression. In veterinary medicine, APIs have only been applied to livestock and dogs with Leishmaniasis. This study aimed to calculate an API to assess its value in cancer-bearing dogs. Serum samples were collected from 55 dogs, and multiple samples were available in 32 dogs. Patients were classified by neoplastic category and survival times (> or <30 and 90 days). The API included two positive and two negative APPs. Lower Paraoxonase-1 (PON-1) levels were found in round-cell tumors, possibly reflecting higher oxidative stress. Moreover, API increased and PON-1 activity decreased in the last sample in dogs that died before the end of the study. Dogs with elevated APIs and C-reactive protein had shorter survival times. An API greater than 0.049 at first sampling was associated with a 3.7-fold higher risk of death. These findings highlight the prognostic potential of APIs in canine cancer.

Acute phase proteins (APPs) are part of the innate immune response, changing during inflammation. An Acute Phase Index (API) is a calculated value that combines multiple APPs. In human medicine, the introduction of APIs has improved outcome monitoring. In veterinary medicine, APIs have been evaluated in livestock and dogs with Leishmaniasis. This study aimed to calculate an API and evaluate its significance in cancer-bearing dogs. Sera were collected from 55 dogs, which were classified by neoplastic category and survival times (> or < than 30 and 90 days). For 32 dogs, multiple samples were available. The API included C-Reactive Protein (CRP) and haptoglobin as positive APPs, and albumin and Paraoxonase-1 (PON-1) as negative APPs. An alternative API excluding PON-1 was calculated. PON-1 levels were lower in round-cell tumors, suggesting increased oxidative stress. Moreover, API increased and PON-1 activity decreased in the last sample in dogs that died before the end of the study. Dogs with shorter survival times showed increased APIs and CRP levels. APIs with and without PON-1 greater than 0.049 and 0.202 at the first sampling were associated with a 3.7- and 4.4-fold higher probability of death, respectively. These results suggest a potential prognostic value of API in dogs with neoplasia.